The potential role of pomegranate and its nano-formulations on cerebral neurons in aluminum chloride induced Alzheimer rat model

The oxidative stress leading to degenerative changes in the brain of Alzheimer’s disease (AD) is evident. Our aim was to evaluate the therapeutic and protective effects of pomegranate extract (PE) and pomegranate extract-loaded nanoparticles (PE nano) in an AlCl 3-induced AD rat model. Nanoparticles were synthesized with a PE load of 0.68% w/w, and 70 male Wistar rats were divided into 7 groups: Group I was the control, Group II received PE., Group III received PE nano for 2 weeks, Group IV received AlCl 3 (50 mg/kg) daily orally for 4 weeks, Group V received PE for 2 weeks, Group VI received PE nano for 2 weeks, and Groups V and VI were started after AlCl 3 administration was stopped. Group VII received PE for 2 weeks and was stopped before AlCl 3 was administered. The Results revealed that the discrimination index in the novel object recognition test was the least in AD rat model but increased in cases protected with PE treated with PE nano. Similar results were shown based on calculating the brain weight/body weight percent. The biomarkers of antioxidant activity (catalase, glutathione and total antioxidant activity) in brain homogenate were significantly increased in groups treated with either PE or PE nano. The thiobarbituric acid reactive substance measured to estimate lipid peroxidation was significantly increased in AD rat model and decreased in groups protected with PE or treated with PE nano. Histopathological studies using hematoxylin and eosin, cresyl violet, and silver stains revealed hyaline degeneration, chromatolysis, and hallmarks of AD; neurofibrillary tangles and the senile plaques in brains of AD rat model. Restoration of the histological architecture, Nissl granules, and minimal appearance of hallmarks of AD characterized brains treated with PE or PE nano. In conclusion, PE was more effective as a protectant than a therapeutic measure in alleviating the antioxidant, lipid peroxidative effects and histopathological hallmarks in AD brains. But, the therapeutic PE-loaded nanoparticles increased the efficacy of active components and produced similar results as the protective PE.     

Effect of sesamol on radiation-induced cytotoxicity in Swiss albino mice

The radio-protective ability of sesamol (SM) at various doses viz., 0, 10, 25, 40, 50, 70 and 100 mg/kg bw, administered intraperitoneally 30 min prior to 9.5 Gy whole-body γ-irradiation was studied in Swiss albino mice. Radiation toxicity and mortality were observed during a period of 30 days and the percentage mortality was calculated. SM pretreatment with 50 mg/kg bw was found to be the most effective dose in maintaining body weight and in reducing the percentage mortality, while 100 mg/kg bw was found to be more effective in maintaining the spleen index and in stimulation of endogenous spleen colony-forming units. Pretreatment with SM (50 mg/kg bw) in mice irradiated with 15 Gy significantly reduced dead, inflammatory, mitotic and goblet cells in irradiated jejunum. SM at 50 mg/kg bw also increased crypt cells, maintained villus height, and prevented mucosal erosion. Nuclear enlargement in epithelial cells was found less in SM-treated mice compared with the irradiated control. The radiation-induced decrease in endogenous antioxidant enzymes (GSH, GST, catalase) and the increase in lipid peroxidation were also reduced by pretreatment with SM [50 and 100 mg/kg bw] at all monitored post-irradiation intervals. There was no protection at a dose less than 25 mg/kg bw.     

Radio-protective effects of melatonin against irradiation-induced oxidative damage in rat peripheral blood

During radiotherapy, ionizing irradiation interacts with biological systems to produce free radicals, which attacks various cellular components. The hematopoietic system is well-known to be radiosensitive and its damage may be life-threatening. Melatonin synergistically acts as an immunostimulator and antioxidant. In this study we used a total of 120 rats with 20 rats in each group. Group 1 did not receive melatonin or irradiation (Control group), Group 2 received only 10 mg/kg melatonin (Mel group), Group 3 exposed to dose of 2 Gy irradiation (2 Gy Rad group), Group 4 exposed to 8 Gy irradiation (8 Gy Rad group), Group 5 received 2 Gy irradiation plus 10 mg/kg melatonin (Mel +2 Gy Rad group) and Group 6 received 8 Gy irradiation plus 10 mg/kg melatonin (Mel+8 Gy Rad group). Following exposure to radiation, five rats from each group were sacrificed at 4, 24, 48 and 72 h. Exposure to different doses of irradiation resulted in a dose-dependent decline in the antioxidant enzymes activity and lymphocyte count (LC) and an increase in the nitric oxide (NO) levels of the serum. Pre-treatment with melatonin (10 mg/kg) ameliorates harmful effects of 2 and 8 Gy irradiation by increasing lymphocyte count(LC) as well as antioxidant enzymes activity and decreasing NO levels at all time-points. In conclusion 10 mg/kg melatonin is likely to be a threshold concentration for significant protection against lower dose of 2 Gy gamma irradiation compared to higher dose of 8 Gy. Therefore, it seems that radio-protective effects of melatonin are dose-dependent.     

Combined efficacy of Vigna radiata (L.) R. Wilczek and Amorphophallus paeoniifolius (Dennst.) Nicolson on serum lipids in albino rats

Coronary Artery Disease (CAD) is a major killer disease throughout the world. Dyslipidemia is a major contributor to the risk of CAD. Several dietary articles traditionally used in India and other South Asian countries reduced dyslipidemia. The present study was undertaken to evaluate the combined effect of Mung bean (Vigna radiata) and Elephant foot yam (Amorphophallus paeoniifolius) on serum lipids and atherogenic indices in albino rats and to compare it with a standard drug Cholestyramine. Thirty healthy albino rats of both sexes (150–200 g) were randomized to 5 groups of 6 animals each. The grouping were done based on the following criteria: Group I: Normal Control Group, Group II: (Standard Group): Cholestyramine resin 5 mg/kg bw, Group III: (Half Dose Group): Drug powder at 540 mg/kg bw, Group IV: (Effective Dose Group): Drug powder at 1080 mg/kg bw, and Group V: (Double Dose Group): Drug powder at 2160 mg/kg bw. Lipid profile was estimated at the beginning and after 30 days of treatment. The Effective and Double doses of the drug reduced Total cholesterol along with levels of Triglycerides, Low density lipoprotein and Very low density lipoprotein levels significantly (p < 0.01) along with a significant (p < 0.01) increase in high density lipoproteins (HDL) in rats. There was also significant (p < 0.01) improvement in atherogenic indices like Castelli Risk Index I, Non HDL C/HDL, Castelli risk Index II, TG/HDL, Atherogenic coefficient and Atherogenic Index of Plasma. The combination of powdered sprouted mung bean and yam powder have excellent lipid lowering potential.     

Ameliorative effect of L-carnitine on lambda-cyhalothrin-induced anatomical and reproductive aberrations in albino mice

The objective of this research was to look at how the pesticide lambda-cyhalothrin (LCT) affected the liver, kidney, testis, and ovary of albino mice; and on morphological and skeletal features of the newborn of treated females. The study also aimed to test the ameliorative effects of L-carnitine (LC) against (LCT). Five sets of mice were created, Group 1 acted as the control, while Group 2 received a high dose of LCT, Group 3 received a high dose of LCT + LC, Group 4 received a low dose of LCT that was a residue of in khat (Qat), and Group 5 received a low dose of LCT + LC. The findings revealed that the treated groups' body weights were reduced significantly, whereas the absolute and relative weights of the liver in all groups were statistically decreased insignificantly. There were histopathological changes in the tissues in groups 2 and 4. While the tissues of the ovary and testis showed recovery in groups 3 and 5. When compared to the control group, the values of the seminiferous tubules parameters were statistically significant in the 3 and 5 groups. The newborn had a high dose of pesticides and showed some malformations in the skeleton. However, in group 3 the skeletal malformation was minimized and in-group 5 the skeleton malformations had completely disappeared. It could be concluded that LCT is highly harmful to mouse tissues and caused neonatal malformations, whereas LC has a marked protective effect against LCT.     

Influence of doxycycline administration on rat embryonic development during organogenesis

This experiment was performed to evaluate the possible embryotoxic and teratogenic effects of doxycycline during rat development. Twenty‐one female rats were used and distributed into three groups equally (seven animals/group). The low dose group received doxycycline at a dose of 5 mg/kg bw/day orally from the 6th to 14th day of gestation. The high dose group received 10 mg/kg bw/day orally for the same period, the Control group received 1 mL distilled water orally for the same period. The dams were dissected on the 20th day of gestation and their fetuses were subjected to morphological, skeletal, and histological examination. Moreover, DNA damage analysis of liver cells of pregnant rats and their fetuses or fetal skull was assessed by Comet assay. The obtained results showed a significant decrease in fetal body weight, several morphological anomalies, and severe lack of ossification on the skull bones, phalanges, and sternum bone as well as shortness in the ulna and radius bones. Histological studies of pregnant rats revealed congestion and dilatation of the central vein of the liver lobules and fatty degeneration of the hepatocytes. In addition, 20 day‐fetuses showed a marked increase of necrotic hepatocytes associated with an increased average of megakaryocytes and periportal leukocytic infiltration. Moreover, doxycycline induced a significant increase in the percentage of DNA damage and tail length of examined samples. Conclusively, doxycycline caused certain fetal abnormalities, so it is advisable to avoid using this drug during pregnancy.     

Is Muta™Mouse insensitive to clastogens?

Several studies suggest that Muta™Mouse is insensitive to clastogens, including the accompanying paper by Mahabir et al., which describes a study with bleomycin, camptothecin, m-AMSA (4′-(9-acridinylamino)-methanesulfon-m-anisidide) and its ortho-analogue, o-AMSA (4′-(9-acridinylamino)-methanesulfon-o-anisidide). Only camptothecin was clastogenic in Muta™Mouse and none of these four compounds induced mutations at the lacZ locus. However, to improve exposure, dose range-finding studies were performed in CD2F1 mice, the parental strain of Muta™Mouse. Male CD2F1 mice (n = 3) were treated with bleomycin (25–100 mg/kg bw, p.o. and i.p.), camptothecin (1–10 mg/kg bw p.o.) and m-AMSA (10–50 mg/kg bw p.o. and 1–5 mg/kg bw i.p.) for 5 days and blood was sampled on day 3 and/or day 6 for analysis by flow cytometry to determine % MN-RETs. Camptothecin (1 mg/kg bw, day 6) induced a 3.6-fold increase in % MN-RET (P < 0.05) but was toxic at higher doses. All day-3 camptothecin samples were positive (P < 0.05). Bleomycin was negative when administered p.o. but positive at all doses on both days when given i.p. (P < 0.05) whereas m-AMSA was negative when given i.p. or orally. Based on these results, male Muta™Mouse mice (5 per group) were dosed daily with bleomycin (50 mg/kg bw) for 5 days or with camptothecin (5 mg/kg bw) for 2 days. Peripheral blood was sampled 24 h after the final dose in each group and tissues were sampled 37 days later. Both compounds induced significant increases in % MN-RET, but only bleomycin induced a significant increase in MF (6-fold in liver, 4.5-fold in kidney and 2-fold in lung) compared with the untreated control. These studies support the view that Muta™Mouse is insensitive to compounds where the genotoxic mechanism of action is predominantly clastogenesis, but demonstrates that the peripheral blood micronucleus test is a useful adjunct to the transgenic gene-mutation assay.     

Alleviation of lindane induced toxicity in testis of Swiss mice (Mus musculus) by combined treatment with vitamin C, vitamin E and alpha-lipoic acid

Mitigation of lindane induced toxicity in testis of Swiss mice by combined treatment with vitamin C, vitamin E and alpha-lipoic acid has been evaluated. Male healthy mice (40), 8-10 weeks old were randomly selected and divided into 4 groups, control (C); lindane (L); antioxidant (A) and antioxidant plus lindane (A+L). Group C animals were administered only the vehicle (olive oil); in group L lindane was administered orally at a dose of 40 mg/kg body wt.; in group A combination of antioxidants at a dose of 125 mg/kg body wt.(vitamin C: 50 mg/kg body wt., vitamin E: 50 mg/kg body wt. and alpha-lipoic acid: 25 mg/kg body wt.) was administered orally; in group A+L both antioxidants (125 mg/kg body wt.) and lindane (40 mg/kg body wt.) were administered at their respective doses. In group A+L antioxidants were administered 1 h prior to lindane administration. All treatments were continuously given for 60 days. Histopathological changes due to lindane intoxication indicated shrunken and distorted seminiferous tubules, sparse Leydig cells and blood vessels and atrophy in the tissue. The testis weight also decreased significantly. Lindane treated group showed increased lipid peroxidation, whereas glutathione, glutathione peroxidase, superoxide dismutase, catalase and protein were significantly decreased compared to control. Lindane induced damage was minimized by administration of antioxidants. Results suggest that combined pretreatment with antioxidants can alleviate the damage caused to testis by lindane.     

Modulation of Carbohydrate Metabolism During <Emphasis Type="Italic">N</Emphasis>-Methyl <Emphasis Type="Italic">N</Emphasis>-Nitrosourea Induced Neurotoxicity in Mice: Role of Curcumin

The present study was carried out to elucidate the effectiveness of curcumin in mitigating the adverse effects caused by N-Methyl N-Nitrosourea (MNU) on mouse cerebellum and cerebrum. Male laca mice received either intravenous MNU treatment at a dose of 10 mg/kg bw in sterile double distilled water, curcumin alone 60 mg/kg bw in drinking water, or combined MNU and curcumin treatment on alternate days for a period of 2 months. The effects of different treatments were studied on carbohydrate metabolizing enzymes viz: hexokinase, glucose-6-phosphatase (G6P), glucose-6-isomerase (G6I), lactate dehydrogenase (LDH), succinate dehydrogenase (SDH) and glycogen levels. Curcumin supplementation to MNU treated mice was able to reduce significantly the activities of the G6P, G6I, hexokinase, LDH, SDH and increased the glycogen contents in both the regions of brain which were altered following MNU treatment. Hence, curcumin shall prove to be effective in ameliorating the adverse effects caused by MNU.     

Hesperidin ameliorates cisplatin induced hepatotoxicity and attenuates oxidative damage,cell apoptosis,and inflammation in rats

Cisplatin is one of the most widely used chemotherapeutic anti-cancer drugs that is associated with multiple systemic toxicities limiting its use. The present study aimed to evaluate the hepato-protective effect of hesperidin against cisplatin-induced toxicity. Thirty-two adult male albino rats were equally split into four groups, the first group served as control received normal saline, the second group (CIS) received a single intraperitoneal dose of cisplatin (7.5 mg/kg bw) on the 22nd day of the experiment, the third group (HES) treated once daily with hesperidin (200 mg/kg bw, orally) for 21 days, and the last group (HES + CIS) pretreated once daily with hesperidin followed by a single intraperitoneal dose of cisplatin. Twenty-four hours later, samples were collected for further investigations. CIS-intoxication resulted in a significant decrease in the erythrogram along with thrombocytopenia leukopenia, and lymphopenia. Furthermore, CIS administration significantly elevated serum activity of liver enzymes, total, and indirect bilirubin as well serum glucose, total cholesterol, and triglycerides levels, meanwhile serum total protein, and globulin levels were significantly reduced. The hepatic MDA was markedly elevated with a concomitant decline in the hepatic antioxidant enzymes and severe alterations in the hepatic tissue architecture in CIS-intoxicated rats. Additionally, CIS-induced overexpression of hepatic Bax, caspase-3, and TNF-α, with no effect on hepatic expression of IL-10. Interestingly, HES pretreatment improved the CIS-induced hemato-biochemical, molecular and histopathological alterations. In conclusion, hesperidin hepato-protective effects against CIS might be mediated by its antioxidant, anti-inflammatory, and anti-apoptotic properties.     

Mutagenicity of 4-nitroquinoline 1-oxide in the MutaMouse.

As part of a collaborative study, the Mammalian Mutagenesis Study Group (MMS), a sub-organization of the Environmental Mutagen Society of Japan (JEMS) conducted mutagenicity tests in MutaMouse. Using a positive selection method, we studied the organ-specificity and time dependence of mutation induction by 4-nitroquinoline 1-oxide (4NQO). A single dose of 4NQO was administered intraperitoneally (7.5 or 15 mg/kg) or orally (200 mg/kg) to groups of male mice. On days 7, 14 and 28 after treatment, we isolated the liver, kidney, lung, spleen, bone marrow, testis and stomach in the intraperitoneal administration experiment and the liver, lung, bone marrow, testis and stomach in the oral administration experiment. In addition, we performed the peripheral blood micronucleus test to evaluate clastogenicity. In the mice treated intraperitoneally at 7.5 mg/kg, we found increased mutant frequency (MF) only in the lung, where the MF did not vary with expression time. In the mice treated at 15 mg/kg, we found increased MF in the liver, bone marrow and lung. In orally treated mice, the MF was high in the lung and liver and very high in the bone marrow and stomach while the increase in the testis was negligible. As the expression time was prolonged, the MF tended to increase in the liver, decrease in the bone marrow, and remain stable in the lung, testis and stomach. The incidence of micronucleus induction in peripheral blood cells was significantly increased (p<0.01) in the 4NQO groups when compared with the vehicle control group by intraperitoneal treatment. Thus, these assay systems appeared to be of use in detecting not only genetic mutation but also chromosomal aberration.     

Studies on the protective effects of caffeic acid and quercetin on chemical-induced hepatotoxicity in rodents.

Caffeic acid and quercetin, the well-known phenolic compounds widely present in the plant kingdom, were investigated for their possible protective effects against paracetamol and CCl4-induced hepatic damage. Paracetamol at the oral dose of 1 g/kg produced 100% mortality in mice while pretreatment of separate groups of animals with caffeic acid (6 mg/kg) and quercetin (10 mg/kg) reduced the death rate to 20% and 30%, respectively. Oral administration of sub-lethal dose of paracetamol (640 mg/kg) produced liver damage in rats as manifested by the significant (P<0.01) rise in serum levels of aminotransferases (aspartate transaminase (AST) and alanine transaminase (ALT)) compared to respective control values. The serum enzyme values were significantly (P<0.01) lowered on pretreatment of rats with either caffeic acid (6 mg/kg) or quercetin (10 mg/kg). Similarly, the hepatotoxic dose of CCl4 (1.5 ml/kg; orally) also raised significantly (P<0.05) the serum AST and ALT levels as compared to control values. The same dose of the caffeic acid and quercetin was able to prevent CCl4-induced rise in serum enzymes. Caffeic acid and quercetin also prevented the CCl4-induced prolongation in pentobarbital sleeping time confirming their hepatoprotectivity. These results indicate that caffeic acid and quercetin exhibited hepatoprotective activity possibly through multiple mechanisms.     

Amelioration of carbon tetrachloride-induced hepatotoxicity and haemotoxicity by aqueous leaf extract of Cnidoscolus aconitifolius in rats

This study was conducted to explore possible protective effect ofCnidoscolus aconitifolius (CA) leaf extract on carbon tetrachloride (CCl4)-induced hepatotoxicity and haemotoxicity in experimental animal models. Thirty six rats of six per group were used in this study. Group I received 10ml/kg normal saline as control. Group II-VI rats were administered with 1.25ml/kg body weight (bwt) of carbon tetrachloride intraperitonealy. Animals in groups III, IV, V and VI were however pre-treated with aqueous extract of Cnidoscolus aconitifolius at 100, 250, 500 and 750mg/kg body weight (bwt) respectively. Administration of CCL4 in untreated rats led to microcytic hypochromic anaemia, thrombocytopenia, increased erythrocyte fragility and stress induced leucocytosis accompanied with significant increase in neutrophils and decrease in lymphocyte counts. CCl4 also led to significant increase in serum transaminases (ALT and AST) and phosphatase (ALP) respectively compared with control animals. Also, CCL4 produced significant increase in serum blood urea nitrogen (BUN) and creatinine compared with normal rats. Pre-treatment with Cnidoscolus aconitifolius leaf extract brought about significant restoration of the haematological parameters to values that were comparable to those of the control with concomitant decrease in the activities of the marker of hepatic damage enzymes (ALT, AST and ALP), in a dose-dependent manner. Similarly, serum levels of blood urea nitrogen (BUN) and creatinine were also brought to near normal by the CA in a dose-dependent manner. From this study, we conclude that pre-exposure to Cnidoscolus aconitifolius leaf extract considerably reduced the effect of CCl4 on the blood parameters and ameliorated hepatic damage by the haloalkane. Keywords: Hepatotoxicity, Haemotoxicity, Carbon tetrachloride, Cnidoscolus aconitifolius, Rats.     

Protective effect of resveratrol against pembrolizumab-induced hepatotoxicity and neurotoxicity in male rats

The present study investigates the effects of resveratrol (RSV) on brain and liver tissues in rats with pembrolizumab (PEMB)-induced toxicity. Obtained for the study were 28 male Sprague-Dawley rats (3–4 months old) which were divided into four groups: Group 1: Control. Group 2: Administered PEMB at 5 mg/kg/day i.p. for a week. Group 3: Administered RSV orally at the dose of 20 mg/kg/day for 30 days by gavage. Group 4: Administered PEMB and RSV at 20 and 5 mg/kg/day RSV, respectively, for 30 days. The results of this study revealed that PEMB leads to a significant increase in thiobarbituric acid reactive substance (TBARS) levels and a significant decrease in glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD) activities, and glutathione (GSH) levels in the liver and brain tissues. The decreased SOD, CAT, GPx activities, and GSH levels increased significantly following RSV treatment in Group 4. The PEMB treatment showed histopathological alterations associated with strong positive cysteinyl aspartic acid-protease-3 (caspase-3) immunoreactivity, while RSV treatment reduced both the expression of caspase-3 protein and the histopathological changes. RSV administration prevents the biochemical, immunological, and histological alterations induced by PEMB. It can be suggested that the lower caspase-3 immunoreactivity in the PEMB + RSV group than in the PEMB group led to an inhibition of RSV on apoptosis.     

Protective effect of omega-3 fatty acid against mercury chloride intoxication in mice

The aim of this study was to investigate the protective effect of omega-3 fatty acid in HgCI₂ toxicity in mice. Levels of malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO) and total sialic acid (TSA), and histopathological changes in selected organs were evaluated. Twenty-eight mice were equally divided into 4 groups, namely Groups I–IV. Group I animals received intraperitoneal (ip) injection of physiological saline solution; Group II animals received ip injection of 0.4 mg/kg/day HgCI₂; Group III animals received ip injection of 0.4 mg/kg/day HgCI₂ in addition to subcutaneous (sc) injection of 0.5 g/kg/day omega-3 fatty acid; and Group IV animals received sc injection of 0.5 g/kg/day omega-3 fatty acid. All treatments lasted 7 days. The levels of MDA, NO and TSA were significantly higher in Group II and lower in Groups III and IV as compared to the Group I. GSH level was the highest in Group IV. In histopathology, severe degeneration in liver and kidney was observed in Group II animals. These degrading changes were seen to be reduced greatly in Group III animals. The results suggested that omega-3 fatty acid might attenuate HgCI₂-induced toxicity by improving antioxidant status and acute phase response in mice.     

Hepatoprotective effects of Solanum nigrum Linn extract against CCl(4)-induced oxidative damage in rats

Solanum nigrum L. (SN) is an herbal plant that has been used as hepatoprotective and anti-inflammation agent in Chinese medicine. In this study, the protective effects of water extract of SN (SNE) against liver damage were evaluated in carbon tetrachloride (CCl4)-induced chronic hepatotoxicity in rats. Sprague-Dawley (SD) rats were orally fed with SNE (0.2, 0.5, and 1.0 g kg(-1) bw) along with administration of CCl4 (20% CCl4/corn oil; 0.5 mL kg(-1) bw) for 6 weeks. The results showed that the treatment of SNE significantly lowered the CCl4-induced serum levels of hepatic enzyme markers (GOT, GPT, ALP, and total bilirubin), superoxide and hydroxyl radical. The hepatic content of GSH, and activities and expressions of SOD, GST Al, and GST Mu that were reduced by CCl4 were brought back to control levels by the supplement of SNE. Liver histopathology showed that SNE reduced the incidence of liver lesions including hepatic cells cloudy swelling, lymphocytes infiltration, hepatic necrosis, and fibrous connective tissue proliferation induced by CCl4 in rats. Therefore, the results of this study suggest that SNE could protect liver against the CCl4-induced oxidative damage in rats, and this hepatoprotective effect might be contributed to its modulation on detoxification enzymes and its antioxidant and free radical scavenger effects.     

Biogenic zinc-oxide nanoparticles of Moringa oleifera leaves abrogates rotenone induced neuroendocrine toxicity by regulation of oxidative stress and acetylcholinesterase activity

Zinc oxide nanoparticles (ZnONPs) from plant origin were postulated to regulate complex hormonal control through the hypothalamus– pituitary–testicular axis and somatic cells due to their unique small size and effective drug delivery to target tissues. This study therefore investigates the biogenic synthesis of zinc oxide nanoparticles (ZnO NPs) from Moringa oleifera leaves on key endocrine hormones (LH, FSH and testosterone), MDA level, antioxidant enzymes (SOD and CAT), acetylcholineesterase (AChE) activity and reactive nitrogen species (NO^?) level in rotenone induced male rat. The animals were divided into six groups (n = 8). Group I was orally given olive oil as vehicle; Group II received 60 mg/kg of rotenone (RTNE) only; Group III (RTNE + ZnONPs) received 60 mg/kg RTNE + 10 mg/kg ZnONPs; Group IV (RTNE + ZnCAP) received 60 mg/kg RTNE + 50 mg/kg zinc capsule; Group V (ZnONPs only) received 10 mg/kg ZnONPs only. Group VI received 50 mg/kg ZnCAP only. The experiment lasted 10 days. TEM and XRD images revealed ZnO NPs. Moreover, the presence of organic molecules in bio-reduction reactions from the FTIR spectrum showed the stabilization of the nanoparticles. Also, animals induced with rotenone exhibited impairment in the leydig cells by depleting LH, FSH, and testosterone levels with reduced AChE activity and significant (p < 0.05) alteration in cerebral enzymatic antioxidants. There was also brain increase in NO^? production: marker of pro-inflammation. Nanotherapeutically, ZnONPs regulated hypothalamus–pituitary–testicular axis via modulation of cerebral NO^?, FSH, LH, testosterone and AChE activity with induction of anti-oxidative enzymes.     

Ginger extract attenuates labetalol induced apoptosis,DNA damage,histological and ultrastructural changes in the heart of rat fetuses

Labetalol is a medication used to treat maternal hypertension during pregnancy. However, it is often associated with many side effects. Recently, several studies have been focused on the protective effect of medicinal plant extracts, such as ginger, against drugs inducing toxicity. Therefore, it has been hypothesized that ginger aqueous extraction can ameliorate labetalol-induced histological, ultrastructural changes, DNA damage, and apoptosis in fetal heart tissue. To achieve the aim of this study, sixty pregnant female albino rats were divided into 4 groups (15 each). Group I (Control). Group II received ginger (200 mg/kg). Group III received labetalol (300 mg/kg). Group IV received labetalol first followed by ginger. All groups were orally injected daily during the organogenesis phase of gestation i.e., from the 6th to the 15th day, and sacrificed at the 20th day of gestation. Results showed that labetalol-induced marked histological and ultrastructural alterations. Also, there was severe DNA damage and an increase in the apoptotic rates determined by Annexin-V/PI dual staining assay. Injection of the ginger aqueous extract caused evident improvement in cardiac tissue, DNA damage, and apoptotic rates. In conclusion, the results suggest that ginger extract could be a potential candidate agent for reducing labetalol-induced cardiotoxicity in the fetal heart of albino rats.     

Influence of halloysite nanotubes on the efficiency of Asparaginase against mice Ehrlich solid carcinoma

Herein, the impact of the halloysite nanotubes to suppress the side effects of Asparaginase (ANase) cellular proliferation was investigated. Methods: A total of 100 adult male mice was employed. These mice were divided into four equal groups; Group 1 (control), Group 2 (ESC group) of a single dose of 0.15 ml Ehrlich cells (2 × 10⁶) intraperitoneal infusion(IP), Group 3 (ESC + ANase group) received six doses equal treatments of Intratumoral (IT) 0.07 ml Aspragnase (7 mg/kg) over two weeks. For two weeks, Group 4 (ESC + ASNase + HNTs) received an IT administration of 0.07 ml Asparaginase stocked on Halloysite nanotubes (HNTs) (30 mg/kg) three times per week. A blood specimen was collected, and the liver was removed to be investigated histologically. Results: TEM measurements for the Halloysite nanoclay showed their tubular cylindrical shape with a mean diameter of 50 nm and an average length of 1 μm, whereas The X-ray diffraction pattern of the Halloysite nanoclay showed their characteristic peaks. ESC increases the serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and bilirubin than control and other groups, even as albumin and total protein were decreasing. After using Halloysite Nanotube, the rates of these variables were enhanced up to 75%. The hepatocytes histological studies showed protection against Ehrlich Solid carcinoma-induced degenerative, necrotic, and inflammatory changes up to 70%. In conclusion, halloysite nanotubes have demonstrated effective removal of Ehrlich solid carcinoma in mice using an ASNase delivery system. It promoted the ASNase to inhibit the adverse effect of ANase's on the liver and remove the tumour cells.