**3. Results and discussion**

### **3.1 Structural properties**

X-ray diffraction (XRD) patterns of prepared Mg2TiO4 nanoparticles milled for different hours via high energy ball milling was taken and is illustrated in **Figure 3**. XRD patterns indicates that for the samples milled for 5 hrs exhibited the peaks corresponding to initial compounds MgO and TiO2 only. When the milling time increases, the intensities of the parent oxide peaks appear to be depressed gradually and the formation of associated MgTi2O5 phase was observed. When the milling time increased to 30 hrs, all the starting oxides peaks are disappeared completely. At the same time high intense diffraction peaks of pure- Mg2TiO4 phase are observed with small significance of MgTiO3 and MgTi2O5 phases. However, when the milling time reached to 35 hrs, the

#### **Figure 3.**

*XRD patterns of the MgO and TiO2 oxides milled for 5, 20, 30 and 35 hrs (adapted with permission from Bhuyan et al., 2020,* @ Springer *[19]).*

sample showed more intensified Mg2TiO4 phases along with small MgTiO3 peak. This signifies that crystallite nature of pure Mg2TiO4 sample enhances and is confirmed from ICSD – PDF # 06–5792. The presence of associated phases such as MgTi2O5 and MgTiO3 in the MgO - TiO2 system is mostly due to the difference in the degree of the incipient mechanical reaction. This can be explained as follows: at the time of milling, the mechanical energy of the grinding media transforms into the given oxide particles that causes structural destruction followed by reduction in particle size [26].

#### **3.2 Williamson - Hall (W - H) method**

The crystallite size of nanoparticles can be determined with several techniques that rely upon the peak width of the X - ray diffraction patterns. In the present study, Williamson-Hall (W-H) plot method as well as Scherrer formula have been chosen in order to understand the origin of the broadening in the XRD peak.

The broadening of XRD peaks is due to crystallite size and strain contributions. The average crystallite size was calculated from XRD peak width based on Debye– Scherrer's equation,

$$D = \frac{k\mathcal{X}}{\beta\_{\text{hkl}}\cos\theta} \tag{1}$$

where *β*hkl is the full width half maximum, *D* is the crystallite size, *k* is the shape factor which is taken as 0.9 for spherical particles, *λ* is the wavelength of incident X-ray radiation (λ = 0.154 nm for Cu-Kα) and *θ* is the Bragg angle of the analyzed peaks.

According to Williamson and Hall, the strain-induced broadening in nanocrystalline powders due to crystal imperfection and distortion was calculated using the formula [35],

$$\varepsilon = \frac{\beta\_{\text{hkl}}}{4 \tan \theta} \tag{2}$$

Here, *ε* is the effective strain associated with mechanical alloying. Now, the total peak broadening is defined as the sum of the contributions of crystallite size and strain present in the material and can be expressed as [36],

$$
\beta\_{\text{hkl}} = \beta\_{\text{D}} + \beta\_{\text{s}} \tag{3}
$$

where *β*D is due to the contribution of crystallite size, *β*ε is due to strain-induced broadening and *β*hkl is the width of the half-maximum intensity of instrumental corrected broadening. This *β*hkl can be calculated by using the relation,

$$\mathcal{J}\_{hkl} = \left[ \left( \boldsymbol{\beta}^{\mathrm{2}}\_{\ \mathrm{\,\,kdl}} \right) \mathrm{Measured} - \left( \boldsymbol{\beta}^{\mathrm{2}}\_{\ \mathrm{\,\,kdl}} \right) \mathrm{Instru} \,\mathrm{mental} \right]^{\mathrm{\,\,k}} \tag{4}$$

If we consider the particle size and strain contributions to line broadening are independent to each other and both have a Cauchy-like profile, then the observed line breadth is the sum of Eqs. (1) and (2) and is given by [35],

$$\mathcal{J}\_{\text{hkl}} = \left[\frac{k\mathcal{X}}{D\cos\theta}\right] + 4\varepsilon\sin\theta \tag{5}$$

By rearranging the above equation, we get,

$$
\beta\_{\text{hll}} \cos \theta = \left[\frac{k\mathcal{A}}{D}\right] + 4\varepsilon \sin \theta \tag{6}
$$

*Synthesis of Nano-Composites Mg2TiO4 Powders via Mechanical Alloying Method… DOI: http://dx.doi.org/10.5772/intechopen.94275*

This is the Williamson- Hall equation, which represents the uniform deformation model. The average crystallite size is estimated for selected peaks of nanocrystalline MTO powders milled for different hours by using Eqs. (1) and (6). The variation of average crystallite size as a function of milling time calculated by both the method is plotted and is depicted in **Figure 4(a)**. It is clear from **Figure 4(a)** that up to 30 hrs of milling the average crystallite size decreases sharply and then attains a constant value. The average crystallite size of the parent sample was found to be nearly 2.5 μm. But for 20 hrs of milling, the crystallite size reduced to 100-120 nm and for 35 hrs of milling it becomes 40-60 nm, as calculated by W-H method. From Scherer formula the average crystallite size for MTO powder are found to be 28 nm and 17 nm, respectively after 20 and 35 hrs of milling. Thus the crystallite size calculated from the Scherer equation is smaller than that of the W-H method. This is due to the fact that the Scherer's equation does not account for the lattice strain effect that causes line broadening.

Mg2TiO4 has an inverse spinel structure and having structural formula *Mg O* [MgTi] 4 and belonging to the cubic space group of Fd3m (227) [15]. The Ti and Mg atoms occupy the tetrahedral (8a) and octahedral (16d) sites and the oxygen atoms are in (32e) site symmetry position [20]. According to Bragg's law [37],

$$2d\sin\theta = n\lambda\tag{7}$$

where, *n* is the order of diffraction and it is usually taken as *n* = 1, λ is the wavelength of incident X-ray and *d* is the spacing between parallel planes of given miller indices *h, k and l*. Since, Mg2TiO4 has cubic structure, so the lattice constants are *a = b = c*. The *d*-spacing is related to the lattice constant *a*, and the miller indices *h, k and l*, by the following relation [37],

$$d = \frac{a}{\sqrt{h^2 + k^2 + l^2}}\tag{8}$$

By using Eq. (7), the lattice constant of selected planes is calculated by following relation,

$$a = \frac{\lambda}{2\sin\theta}\sqrt{h^2 + k^2 + l^2} \tag{9}$$

The variation of lattice parameter as a function of different milling time is plotted and is illustrated as inset **Figure 4(a)**. The results showed that the lattice constant decreases with increase of milling time from 8.436 Å to a stable value of 8.412 Å. This difference in lattice constant stipulates the occurrence of atomic disorder due to the milling process. That means the grinding of the powders via high energy ball milling techniques not only reduces the crystallite size into nanoscale range (< 100 nm) but also causes in the enhancement of lattice strain. Thus, the net X-ray line broadening is due to decrease of crystallite size, development of lattice strains and also due to the instrumental effects. Normally, crystallite size is a measure of the size of a coherently diffracting domain. So, when the crystallites of the materials are <100 nm, they have very less number of parallel diffraction planes that causes broadened diffraction peaks. Similarly, the non-uniform strains arises out of heavy plastic deformation during the course of high energy mechanical milling process that causes broadening of the diffraction peaks [35].

The milling dependence of internal microstrain (*e*) of mechanically derived nanocrystalline -MTO powders was evaluated. The graph between 4sin*θ*/*λ* (taken along *x*-axis) and *β*hkl cos*θ*/*λ* (taken along *y*-axis) for selected diffraction

**Figure 4.**

*(a) Variations of average crystallite size and lattice parameter (inset) with milling time and (b) variation of lattice strain with milling time. Inset: W-H plot for 35 hrs milled powders. (adapted with permission from Bhuyan et al., 2020,* @ Springer *[19]).*

peaks for 35 hrs milled MTO nano-powders, is plotted and is depicted in inset **Figure 4(b)**. In the present case, the crystal is considered as isotropic in nature and it is assumed that the properties of material do not depend on the direction along which it is measured. From inset **Figure 4(b)**, (called W-H plot), it shows that

*Synthesis of Nano-Composites Mg2TiO4 Powders via Mechanical Alloying Method… DOI: http://dx.doi.org/10.5772/intechopen.94275*

the data points are not much deviated from the straight line suggesting isotropic nature of the strain. From the linear fit of the data, the average crystallite, *D* was estimated from the y-intercept and the microstrain (*ε*) from the slope of the fit (inset **Figure 4(b)**). For 35 hrs milled powders, the crystallite size is found to be approximately 38 nm and microstrain is around 9.01× 10−3 respectively. Thus from the W-H analysis it is clear that the broadening of the X-ray peaks is due to the contribution of smaller crystallite size and the induction of strain. Further, it was noticed that with increase in milling duration the internal microstrain increases and it attains a constant value after a particular milling period.


**1. Introduction**

Obesity is one of the most common nutritional problems worldwide, currently reaching epidemic proportions. This pathology was previously considered typical in developed countries, but nowadays it also shows a high prevalence in underdeveloped countries. According to figures from the World Health Organization (WHO), in 2019 more than 1.9 billion adults aged ≥18 years were overweight, and of them more than 650 million were obese [1]. Since 1975 the worldwide prevalence of obesity has tripled, thus leading to a major public health problem. Obesity is associated with a large number of comorbidities, such as type 2 diabetes mellitus, hypertension, dyslipidemia, non-alcoholic fatty liver disease and cardiovascular diseases, among others. Furthermore, according to the WHO, people with obesity have a 50 to 150% increased risk of death from any cause compared to individuals with normal weight [2].

Hypocaloric diets and physical activity based treatments for overweight and obesity represent the first line of therapy. Due to the difficulty in achieving and maintaining an adequate adherence to this treatment, many people often turn to nutritional supplements that promise to help them lose weight in the short run or at least, to maintain it. For many people it is an easy solution, which enables them not to modify their lifestyle too much. In

**Citation:** Andueza, N.; Giner, R.M.; Portillo, M.P. Risks Associated with the Use of Garcinia as a Nutritional Complement to Lose Weight. *Nutrients* **2021**, *13*, 450. https:// doi.org/10.3390/nu13020450

Academic Editor: Antonella Amato Received: 4 December 2020 Accepted: 24 January 2021 Published: 29 January 2021

**Publisher's Note:** MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

**Copyright:** © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

many instances, the motivation for the use of these supplements is due to aesthetic reasons, since the beauty standards that mark our society today encompass being slim.

These supplements work through five basic mechanisms, these being stimulation of thermogenesis, reduction in lipogenesis, increase in lipolysis, suppression of appetite, and decrease in lipid absorption. Among these nutritional supplements we find those based on plant extracts, which have been used for many centuries in the Eastern world. Nowadays, their use has become more and more prevalent throughout the world. Among them, *Garcinia cambogia* is one of the most promoted as a potential anti-obesity agent and has received a lot of attention in the media [3].

Although the current consumption of herbs and dietary supplements is unknown, in a study carried out in six European countries, it was estimated that 18.8% of the 2358 consumers selected for the study consumed one or more dietary supplements, not taking into account herbal products. The percentages of plant food supplement consumers were 9.6% in Finland, 16.9% in Germany, 22.7% in Italy, 17.9% in Romania, 18.0% in Spain and 19.1% in the United Kingdom [4].

The aim of this review is to gather the reported information concerning both the effectiveness and the side-effects of nutritional supplements based on *Garcinia cambogia* to promote weight loss. In addition, the efficacy of other *Garcinia* species is also presented. For this purpose, a selective literature search in PubMed and Cochrane databases was performed. To search for the effects on body weight loss, the terms Garcinia, HCA, weight loss, fat mass and obesity were introduced, adding "and", "or", "not" to improve the classification. In addition, the filters "clinical trial" and "meta-analysis" were used. To search for toxic effects, the terms Garcinia, HCA and toxic effects were used. In the Cochrane Library database we sought the term "Garcinia" in the title or the abstract in meta-analyses and clinical trials. The search was extended to a total of 25 years (Figure 1).

**Figure 1.** Flow chart showing the process for the inclusions of articles.

#### **2. Active Principle and Mechanisms of Action**

The genus *Garcinia,* native to Asia and Africa, belongs to the *Clusiaceae* family and includes more than 300 species, such as *Garcinia cambogia* (Figure 2)*, Garcinia mangostana* and *Garcinia atroviridis* [5]. Potential therapeutic effects, such as anti-obesity, anti-ulcerogenic, antioxidant, anti-diabetes, anti-fungal, anti-inflammatory and anti-neoplasic [6], have been attributed to this genus. This has led to multiple investigations by pharmaceutical companies [5]. Some of the bioactive compounds isolated from Garcinia are garcinol, isogarcin, ( −)-hydroxycitric acid (HCA), mangostin, and xanthoquimol [6]. It should be noted that out of the species mentioned above, *Garcina cambogia* is the most used as a nutritional supplement for weight loss or maintenance. The anti-obesity properties have been attributed to HCA, which is present in the rind or epicarp of the fruit and represents 20–30% of the dry weight [7]. Many food supplements containing HCA are currently marketed for weight reduction.

**Figure 2.** Tree, branch, and fruit of *Garcinia cambogia*.

The effects of HCA are associated with a reduction in food intake via serotonin level regulation and metabolic modifications, such as an increase in fat oxidation, a decrease in de novo lipogenesis and the stimulation of hepatic glycogenesis, thus promoting energy expenditure. HCA is a competitive inhibitor of adenosine triphosphate (ATP)-citrate lyase, an enzyme that catalyzes the extramitochondrial breakdown of citrate into oxalacetate and acetyl-CoA, thus limiting the availability of acetyl-CoA, a compound that plays a key role in the synthesis of fatty acids in diets rich in carbohydrates (Figure 3).

**Figure 3.** Mechanisms of action of hydroxycitric acid (HCA). CPT: Carnitine palmitoyltransferase.

#### **3. Effectiveness of Garcinia to Lose and Maintain Body Weight**

In in vitro studies, HCA has been shown to inhibit fatty acid synthesis [8]. Specifically, in isolated hepatocytes, HCA inhibits the synthesis of fatty acids from glucose, but not from acetate. Therefore, HCA is an inhibitor of lipogenesis only if cytoplasmic acetyl-CoA is produced by ATP-citrate lyase. Nevertheless, fatty acid synthesis is able to continue as long as acetate, another acetyl-CoA precursor, is available. As the synthesis of acetyl-CoA is reduced, that of malonyl-CoA is reduced too, thus decreasing the negative feedback of carnitine acyltransferase. This produces an increase in lipid transport in the mitochondria and inefficient oxidation, that promotes the formation of ketone bodies. These molecules can pass into the bloodstream and reach the brain, where they constitute an energy reserve in the event of fasting [8].

In preclinical studies using animal models, chronic oral administration of HCA to rats significantly reduces food intake in the first hour after administration, together with body weight and concentrations of cholesterol, triglycerides and fatty acids. When evaluating the acute and chronic effects of HCA on energy metabolism in mice, it was observed that

oral administration of 10 mg increased serum concentration of free fatty acids and glycogen concentration in skeletal muscle [9].

Leonhardt et al. (2002) studied the long-term effect of HCA in male Sprague–Dawley rats after a notable body weight loss in two different experiments. Each experiment had 23 or 24 rats, respectively [10].  Both diets were supplemented with 3% HCA. HCA produced a long-term reduction in body weight recovery in both groups (in both rats fed 1% fat or 12% fat diets). However, only HCA produced a long-term suppressive effect in the case of the group of rats fed the 12% fat diet. No effect on plasma β-hydroxybutyrate levels was observed, so the hypothesis that increased fatty acid oxidation in the liver is involved in suppressing food intake by HCA was not supported by these results [11]. In another study, young lean and obese female Zucker rats were fed a diet (70% glucose, 1% corn oil) supplemented with HCA (52.6 mmol/kg diet) for 39 days. Amongst the lean rats, HCA decreased food intake, body weight, the percent of body fat, and fat cell size. Amongst the obese rats, food intake and body weight were lowered, but body fat percentage remained unchanged [10].

In other studies, instead of isolated HCA, extracts of Garcinia were used for supplementation. Saito et al. (2005) studied the ability of a *Garcinia cambogia* extract, containing HCA, to suppress the accumulation of body fat in growing male obese Zucker rats (6 weeks) [12]. They were given diets containing different amounts of the extract, which provided 10, 51, 102 or 154 mmol of HCA/kg of diet, respectively, for 92–93 days. Rats fed the highest amount of extract, and therefore receiving the highest dose of HCA (154 mmol HCA/kg diet), significantly decreased epididymal fat accumulation, compared to the other groups.

Table 1 presents a summary of the results obtained in 20 reported intervention studies in humans [13–32]. In 12 studies, statistically significant reductions in body weight were observed [14,15,18–22,26–28,30,31]. Conversely, the supplementation turned out to be ineffective in the remaining studies [13,16,17,23–25,29,32]. In the studies where significant weight loss was observed, the average value was between 2 and 6 kg in 2–4 months, with the exception of one where a loss of 14 kg was induced in 6 months [31]. Interestingly, in 11 studies [19–21,23,24,26,27,29–32], significant reductions in other parameters, such as waist and hip circumference, triglycerides, cholesterol and glucose were also observed regardless of body weight loss. It was specified in the vast majority of the studies that the supplement should be consumed approximately half an hour before meals. Splitting the doses of HCA has also been shown to be more effective than utilizing the same amount given as a single dose.

**Table 1.** Characteristics and results of published intervention studies in humans.

**Table1.***Cont*.

**Table 1.** *Cont*.

**Table 1.** *Cont*.

BMI: body mass index; HCA: hydroxycitric acid; HOMA-IR: insulin resistance index, MCT: medium chain triglyceride; TG: triglycerides; IWQOL: impact of weight on quality of life—lite.

> Of note, important differences in the experimental design can be observed among the reported studies. The number of participants ranged from 11 to 214. The fact that the majority of the studies had a small sample size limits the reliability of the results. In addition, in some cases there is a lack of proportion between men and women. The inclusion of both genders is important in order to determine whether there is sexual dimorphism in the effectiveness of the nutritional supplement. Conversely, in all the selected studies, the participants were overweight or obese (based on body mass index) and the duration of treatments ranged from 2 to 4 months in the majority studies, with the exception of two longer ones, in which the duration was 6 or 6.5 months.

> The variability is also observed in the type of supplement administered. Upon that, *Garcinia cambogia*/HCA was used in 15 studies, *Garcinia mangostana* in four studies and *Garcinia artroviridis* in one study. Lastly, in some cases HCA or Garcinia appeared to be combined with other ingredients, such as glucomannan (fiber), *Sphaeranthus indicus* or *Coffea arabica*. Consequently, it is not possible to determine whether the effect produced was due to the HCA content, to other ingredients, or to a combination of the effects of the different ingredients. The dose administered is another differential aspect among the studies. Last of all, the presentation of the supplement is different (pills, capsules or sachets). It is indicated in all cases that the supplement should be consumed before the meal (approximately half an hour before).

> Differences in other aspects of the experimental design, such as diet and physical activity can also be found. In some studies, the participants were instructed to continue with their usual diet and physical activity, while in others they were given specific instructions. Lastly, in others they were prescribed a hypocaloric diet along with specific practice of regular physical activity.

Some of these differential aspects could explain the lack of effect observed in several studies, for instance, the lowest sample size in the studies reported by Kovacs et al. (2001) [16], Kovacs et al. (2001) [17] and Watanabe et al. (2018) [32] In the study reported by Heymsfield et al. (1998) [13], *Garcinia cambogia* was not effective since the diet was low in energy and high in fiber. The amount of fiber could have inhibited the gastrointestinal absorption of HCA (active compound in *Garcinia cambogia*) and the low energy supplied (approximately 1200 Kcal) could have affected the usefulness of HCA. In addition, the dose of HCA was lower than that used in other studies. Another parameter that could have an influence was the excess of calcium used to stabilize HCA, that could have reduced the solubility of this bioactive compound, and therefore its bioavailability [8]. In a similar way, the lack of effect in the studies carried out by Roongpisuthipong et al. (2007) [21] and Vasques et al. (2014) [29] could be related to the low amount of energy provided by the diet (1000 Kcal/d and 1500 Kcal/d, respectively). In the study conducted by Vasques et al. (2008) [23], the only apparent potential reason could be that neither dieting, nor practicing physical activity were recommended. In contrast, in all the studies in which positive results were obtained, a healthy lifestyle was either prescribed or recommended. Last of all, in the studies conducted by Kim et al. (2011) [24] and Hayamizu et al. (2003) [18], in an Asian population, it is believed that the fact that the fruit of the Garcinia is of common use as part of the traditional diet, could have led to a reduced susceptibility to its effects.

Onakpoya et al. (2011) published a systematic review and meta-analysis of randomized clinical trials devoted to evaluating the effectiveness of Garcinia extracts as weight reduction agents [33]. The authors concluded that these extracts generated short-term weight loss. However, the scale of this effect was small, since it was not statistically significant when only rigorous randomized clinical trials were considered. Therefore, the clinical relevance of these products appears to be questionable and they do not represent an altogether effective measure of the treatment of overweight and obesity.

#### **4. Negative Effects on Health**

#### *4.1. Animal Toxicity Studies*

Studies of acute, short-term, sub-chronic, and chronic toxicity, as well as studies of genotoxicity, cytotoxicity and toxicity in reproduction, have been conducted in different animal species, although mainly in rats and rabbits. These studies have shown that Garcinia/HCA have good safety profiles, so that they may be used as nutritional supplements for the treatment of obesity [34–36].

Ohia et al. (2002) evaluated the effects of Super Citri-Max ™, a novel calcium/potassium-HCA extract (HCA-SX), containing 60% HCA, administered for 14 days. This extract is considerably more soluble and bioavailable than calcium-based HCA ingredients [37]. The study was conducted in Albino rats (males and females) fed ad libitum, treated with a dose of 5000 mg/kg (through a gastric probe), which is equivalent to 350 g or 233 times the maximum dose of 1.5 g/day of HCA in humans. The authors did not report any death or significant clinical changes. Furthermore, no significant tissue injuries were observed during the necropsy, which led them to suggest that the LD50 oral administration of HCA-SX in rats was over 5000 mg/kg. Similarly, in another study carried out by the Wil Research Laboratories, it was shown that 5000 mg HCA/kg of body weight did not produce visible symptoms of toxicity or death in animal models. In line with these studies, Clouatre et al. (2013) defended that HCA was extremely safe and this was corroborated by various reviews where it was claimed that HCA from *Garcinia cambogia* had a protective effect on the liver [38].

Shara et al. (2003) analyzed the effects of HCA intake on weight, testicular and liver lipid peroxidation, and DNA fragmentation, in addition to possible histopathological changes in Sprague–Dawley rats [39]. The animals received 0.2, 2.0, or 5.0% HCA (100–2500 mg/kg) in their diet, equivalent to approximately 100, 1000, and 2500 mg/kg/day, respectively, in humans. The lowest dose was equivalent to the daily recommended dosage in humans, but the doses of 2.0 and 5.0% are 10 to 25 times higher doses. The rats were

euthanized at 30, 60, and 90 days of treatment. After 90 days of HCA administration, rats showed decreased body weight, without changes in liver or testicular lipid peroxidation or in DNA fragmentation In a follow-up study, the same authors did not find differences in the weight of various organs. Moreover, no haematological or biochemical disorders or significant histopathological changes or mortality differences were found [40].

As an exception, Kim et al. (2013) in a study addressed in rats fed a high-fat diet (45% of total energy), it was shown that after 16 weeks of treatment with *Garcinia cambogia* (1%, *w/w*, 60% HCA) oxidative stress, inflammation and liver fibrosis were triggered [41]. Consequently, it appears that the form of HCA regarding its extraction process and the residual compounds, among other factors, may spur differences between study outcomes [42].

Toxicological studies have been also addressed with other Garcinia species. Farombi et al. (2013) carried out a study in adult male Wistar rats randomly assigned to four groups of 10 rats each group given *Garcinia kola* orally at different doses (0, 250, 500 and 1000 mg/kg) for 6 weeks [43]. After conducting the study, it was concluded that the administration of *Garcinia kola* increased the antioxidant status and did not produce adverse effects on the liver, testicles and sperm. Saiyed et al. (2015) performed various toxicological studies both in vitro and in animals to evaluate the safety of Meratrim™, a supplement that contains *Garcinia mangostana* [44]. Meratrim™ was determined to be non-irritating to the skin, mildly irritating to the eyes, not mutagenic, and the no-observed-adverse-effect level (NOAEL) for this supplement was 1000 mg/kg body weight/day (in Sprague–Dawley rats). The authors concluded that the safety of Meratrim was demonstrated given the results observed in this study, added to the clinical trials of tolerability already carried out.


**5. Conclusions**

The alpha-emitting radionuclides of 223Ra and 225Ra are a targeted alpha emitter radiopharmaceutical used to treat prostate cancer. The properties and absorbed dose value of those radiopharmaceuticals in body organs are reviewed in this chapter. Total body absorbed dose value (Gy/Bq) per intravenous injections of 223Ra was higher than 225Ac radiopharmaceuticals. This difference is related to the energy of alpha particles and the half-life of the radiopharmaceuticals. The results of this study will assist in evaluating and analyzing human body organ doses from the application of 223Ra and 225Ac that are used in mCRPC patients. The main obstacles using of 223Ra and 225Ac radiopharmaceuticals are that the daughter nuclides will always dissociate from the targeting construct upon their formation. Therefore, they can make unwanted doses in other organs.

## **Conflict of interest**

The authors declare no conflict of interest.

*Radium-223 and Actinium-225 α-Emitter Radiopharmaceuticals in Treatment… DOI: http://dx.doi.org/10.5772/intechopen.99756*


*4.2.1 Glutathione*

*Antioxidants*

*4.1.3 Glutathione perioxidases (GPx)*

membranes and oxidized lipoproteins [30].

such as glutathione, vitamin C and E, Se, and GPx [3].

**4.2 Nonenzymatic antioxidants**

selenium independent [34].

*<IP_ADDRESS> Application*

CAT enzyme is used in the textile industry for H2O2 removal from fabrics, to make sure the material is peroxide free. Recently, esthetics industries have begun to use CAT enzyme in facial masks, as the combination of CAT enzyme with H2O2 on the face can be used to increase cellular oxygenation in the upper layers of the epidermis [3].

Glutathione peroxidase (EC <IP_ADDRESS>) contains a single selenocysteine residue in each of the four identical subunits, which is important for enzyme activity. GPx (80 kDa) is an imperative intracellular enzyme that catalyzes H2O2 to water and lipid peroxides to their corresponding alcohols mainly in the mitochondria and sometimes in the cytosol. In mammals, there are five GPx isoenzymes. Though their expression is ubiquitous, the level of each isoform differs depending on their tissue type. Mitochondrial and cytosolic glutathione peroxidase (GPx1 or cGPx) reduces

GPx1 is the main ubiquitous selenoperoxidase present in most cells; found in the cytosolic, mitochondrial, and peroxisomal compartments. It is an important antioxidant enzyme required in the detoxification of H2O2 and lipid hydroperoxides and preventing DNA, protein and lipids damage by harmful accumulation of intracellular H2O2 [33]. GPx1 uses GHS as an obligate co-substrate in the reduction of H2O2 to water [32]. Phospholipid hydroperoxidase glutathione (PHGPX) is found in most tissues and can directly reduce the phospholipid hydroperoxides, fatty acid hydroperoxides, and cholesterol hydroperoxides that are produced in peroxidized

GPx4 is found in both the cytosol and the membrane fraction, and is highly expressed in renal epithelial cells and tests. Cytosolic GPx2 or extracellular GPx3 is inadequately found in nearly all tissues except for the gastrointestinal tract and kidney. In recent, GPx5, a new kind, expressed particularly in mouse epididymis, is

Several studies underlined the clinical importance of GPx. In addition, GPx, especially GPx1, have been implicated in the progression and prevention of many frequent and complex diseases, including cancer and cardiovascular disease [34, 35].

GPx is an important antioxidant enzyme in the body. Glutathione (GHS), the master antioxidant, is important for GPx levels due to the closely linked relationship; GHS is a tripeptide that protects the cells against the negative effects of pollution and functions as the body's immune system booster. GHS plays an essential role in red blood cells to remain intact and protects white blood cells, which are responsible for the immune system. An antioxidant's role is specifically essential for the brain because it is sensitive to the presence of free radicals. To increase the body's protection from free radicals, it is imperative to combine certain antioxidants

In previous decades, there has been increasing evidence that large amounts of antioxidants present in our diet contribute to the antioxidant defense system by preventing oxidative stress and specific human diseases. Phytochemicals, the plant-derived compounds, are one of the classes of the dietary factors, which play an essential role in functions of the body. Food materials contain a number of natural compounds reported to have antioxidant characteristics due to the presence

fatty acid hydroperoxides and H2O2 at the expense of glutathione [32].

**10**

Glutathione (γ-glutamyl-cysteinyl-glycine; GSH) is a tripeptide and is the most abundant intracellular antioxidant protecting normal cells from oxidative injury due to its role as a substrate of ROS scavenging enzymes. Glutathione is primarily present in its reduced form (GSH) in normal conditions, with only a small amount being found in the fully oxidized state (GSSG) [41]. Glutathione functions as a nonenzymatic antioxidant through free radical scavenging in cells and serves as a cofactor for several enzymes, include GPx, glutathione reductase (GR), and glutathione transferase (GST) [42, 43].

### *<IP_ADDRESS> Application*

Recently, there is a new era of therapeutic applications of glutathione through the association of decreased GSH levels with the common features of aging and a wide range of pathological conditions, including neurodegenerative disorders. Remarkably, depletion and alterations of GSH in its metabolism appear to be crucial in the onset of Parkinson's disease [44].


Preface

This book presents the most recent environmental studies on remote sensing applications. Different sensors that start in both active and passive sensors are used in remote sensing applications. While passive remote sensing simply measures the electromagnetic radiation reflected from the target, active remote sensing transmits and measures electromagnetic radiation that is both emitted and reflected. Wide sensor coverage starts with satellite platforms and extends to unmanned aircraft vehicles (UAVs). What distinguishes a drone from a UAV? An unmanned aircraft or vessel that is piloted remotely or automatically is referred to as a drone. A UAV is a flying object without a pilot.

Remote sensing is a tool used for gathering target information without any physical/direct contact with the Earth's surface. It is a widely used science for the identification and mapping of the various objects/materials present on the Earth's crust. The electromagnetic wavelength ranges from 0.38 µm to 100 cm, which is visible to the microwave region and is utilized for capturing the information from the Earth's surface along with different sensors to capture the electromagnetic spectrum's energy. This technique is useful for monitoring, protecting, and managing diverse natural resources and land cover.

This book covers a variety of applications, including crop monitoring, ice automatic mapping, carbon offset forests, and image processing.

Chapter 1 is an introductory chapter that presents the novel Marghany-Based Genetic Algorithm (MBGA) for automatically detecting ice covers in Synthetic Aperture Radar (SAR) data. The MBGA is designed as discrete steps in a modified genetic algorithm (GA).

Chapter 2 highlights recent advances in SAR systems and their applications in crop growth monitoring. It provides an overview of recent advancements in SAR systems, a summary of SAR information sources, the applications in crop monitoring including crop classification, crop parameter estimation, and change detection, and perspectives for future application development.

Chapter 3 demonstrates a series of optical satellite data, specifically LANDSAT 8, in tracking the carbon offset identification in Malaysian forests. It demonstrates an excellent method for tracking and monitoring deforestation in Malaysia.

Chapter 4 provides an overview of the principles and applications of optical remote sensing in planetary science. It briefly introduces the planetary space environment before discussing the principles of optical remote sensing and planetary optical radiations. The chapter ends with a discussion of current and future optical remote sensing plans in China.

Chapter 5 scrutinizes a significant image enhancement tutorial. It considers both histogram modification and transform domain methods as well as hybrid methods. Furthermore, it proposes a new hybrid algorithm for remote sensing image enhancement. Quality metrics such as Contrast Gain, Enhancement Measurement, Discrete Entropy, and Average Mean Brightness Error are also shown for objective comparison.

Chapter 6 serves as an excellent tool for identifying geological features. It shows how to distinguish between various minerals and lithologies using ASTER satellite data's short-wave infrared (SWIR) and thermal infrared (TIR) spectral bands. It also goes into detail about the value of integrated datasets from SWIR- and TIR-derived results and how to use them to demarcate different litho-units.

Chapter 7 presents transproc, a reconfigurable generic processor that can execute operations related to linear transformations like Fast Fourier Transform (FFT) and Forward Discrete Cosine Transform. (FDCT), or Forward Discrete Wavelet Transform (FDWT). A graph-theoretic lemma is used to find the applicability of such a processor to calculate the flow graph-related parallel operations found in these linear transformations. The architecture level design and processing element level design are also demonstrated in this chapter.

Chapter 8 introduces a technique based on a UAV. In this chapter, the multispectral images acquired by the UAV are exploited to establish a method to identify which banana regions were infected or uninfected with Fusarium wilt disease. The results suggest that UAV-based multispectral imagery with a red-edge band is effective to identify banana Fusarium wilt disease and that the CIRE had the best performance.

Finally, Chapter 9 considers various aspects of the optical and radiolocation sensing and imaging of the Earth's surface from space. These sensors (the payload), being placed on the satellite bus (platform), cannot be used for the satellite mission without its other subsystems. The mission itself, as well as the payload's successful operation and image-providing capability, essentially depends on Satellite Control System SCS and its performance.

I wish to convey my appreciation to the staff at IntechOpen, especially Editorial Project Manager Ms. Karmen Đaleta. Without their commitment and support, this book would not have been possible.

> **Dr. Maged Marghany** Professor, Director, Global Geoinformation, Sdn. Bhd., Kuala Lumpur, Malaysia

## **Chapter 1**


**Chapter 9 157**

Biotechnology in Agricultural Policies of Sub-Saharan Africa *by Joel W. Ochieng and Anthony Ananga*

Preface

Bioeconomy, as a new branch of industrial processes, was created as a result of the analysis of methods of using raw materials, technological processes in the use of these raw materials, and receipt of various types of material goods. Without questioning the legitimacy of the need to produce many products, technologies that use natural resources pose a serious burden to the environment. For these reasons, the concept of bioeconomy as a new industrial branch was introduced in 2012. Bioeconomy is based mainly on raw materials of biological origin, including so-called waste biomass. By definition, bioeconomy should include a wide range of raw materials and the development of technology for their processing, with a minimum environmental burden. Initially, it was assumed that bioeconomy technologies would completely eliminate the production of waste. According to recent research and views, it is theoretically possible to significantly reduce post-production waste in bioeconomic processes. However, known technological processes using biomass as a raw material require an energy supply. This, in turn, causes emissions of carbon dioxide into the atmosphere, regardless of whether this energy comes from coal and oil, or from the use of biofuels and bioliquids. It is also possible to use other renewable energy sources, such as wind, water, or solar energy, but the LCA analysis of these sources also shows emissions in this cycle. Therefore, complete elimination of all waste, including waste heat as one of the forms of mass and energy exchange, from technological processes or the possibility of their full use is not possible. Therefore, bioeconomic processes require in-depth analysis taking into account such criteria as: rational use of available resources of raw materials, the necessary environmental needs for these raw materials, progressive climate change, preservation of biodiversity, soil condition, water, and air. These criteria fall into the category of environmental criteria. In the category of social criteria, we can distinguish: access to clean air, access to food, preservation of soil ownership, process transparency and access to information, employment, and health protection. In the economic criteria category, there is one important criterion regarding the cost and efficiency of bioeconomic processes. The rational use of available raw materials requires the development and implementation of appropriate technologies that should take into account environmental, social, and economic criteria. For this reason, the need to develop a book with the working title "Bioeconomy" that covers the basics and legitimacy of conducting activities in this field was recognized. This book organizes definitions and presents the updated research in the scope of possibilities of implementing bioeconomic processes. Unfortunately, the degree of research development in the scope of these processes is still at the level of discussion in the area of bioeconomy development strategy, and even concepts and their interpretations. Out of many proposed chapters, nine studies were selected. These nine chapters fall within the scope of criteria covering bioeconomic processes. The accepted chapters cover various but partial aspects of these processes. This resulted in the title of the book presented being "Elements of Bioeconomy". Due to various aspects of bioeconomic processes covered in the accepted chapters, it was impossible to divide the content of the monograph into

relevant thematic sections.