Ahmed E. Abdel Moneim

The protective effect of flaxseed oil on lead acetate-induced renal toxicity in rats

Lead is a toxic metal inducing many destructive effects leading to a broad range of physiological, biochemical, and neurological dysfunctions in humans. Here, we investigated the effects of flaxseed oil (1000 mg/kg) on the outcome of renal cytotoxicity induced by lead acetate (20mg/kg) in male rats. Lead induced injury of the renal tissue. This was evidenced (i) as increases in lead concentration in the kidney, (ii) as increases in the histopathological damage of the renal tissue, (iii) as increases in uric acid, urea and creatinine, (iv) as increases in lipid peroxidation, nitric oxide and reactive oxygen species, and (v) as lowered glutathione levels and decreased activities of catalase and superoxide dismutase, glutathione reductase, glutathione-S-transferase, and glutathione peroxidase, respectively. All these lead-induced parameters were significantly altered during flaxseed oil treatment. Therefore, our study suggests the role of flaxseed oil in limiting renal cytotoxicity-induced by lead acetate as a model for lead toxicity.

The neuroprotective effects of purslane (Portulaca oleracea) on rotenone-induced biochemical changes and apoptosis in brain of rat.

Purslane (Portulaca oleraceae L.), a member of the Portulacaceae family, is widespread as a weed and has been ranked as the eighth most common plant in the world. In order to evaluate purslane herbal aqueous juice as a neuroprotective agent, the antioxidant activity of purslane juice was assessed in vitro and the neuroprotective effects of purslane (1.5 mL/Kg bwt) on rotenone (12 mg/Kg bwt for 12 days) induced biochemical changes and apoptosis in striatum of rats were also examined. The repeated administration of rotenone produced dramatic increases in intercellular content of calcium, dopamine metabolites and apoptosis in the striatum. In addition, rotenone administration caused significant decrease in complex I activity. These biochemical changes and apoptosis inductions were effectively counteracted by administration of purslane. Overall, the present study demonstrated the neuroprotective role of purslane in the striatum and proposes its prophylactic potential against developing brain damage and Parkinsons disease induction followed by rotenone administration, and that purslane may be considered as a potential neuroprotective agent against environmental factors affecting the function of the dopaminergic system.

The potential protective role of Physalis peruviana L. fruit in cadmium-induced hepatotoxicity and nephrotoxicity

This study aimed to investigate the potential protective role of Physalis peruviana L. (family Solanaceae) against cadmium-induced hepatorenal toxicity in Wistar rats. Herein, cadmium chloride (CdCl2) (6.5 mg/kg bwt/day) was intraperitoneally injected for 5 days, and methanolic extract of physalis (MEPh) was pre-administered to a group of Cd-treated rats by an oral administration at a daily dose of 200 mg/kg bwt for 5 days. The findings revealed that CdCl2 injection induced significant decreases in kidney weight and kidney index. Cadmium intoxication increased the activities of liver enzymes and the bilirubin level, in addition to the levels of uric acid, urea and creatinine were increased in the serum. The pre-administration of MEPh alleviated hepatorenal toxicity in Cd-treated rats. Physalis was noted to play a good hepatorenal protective role, reducing lipid peroxidation, nitric oxide, and enhancing enzymatic activities and non-enzymatic antioxidant molecule, glutathione, in hepatic and renal tissues of Cd-treated rats. Moreover, physalis treatment was able to reverse the histopathological changes in liver and kidney tissues and also increased the expression of Bcl-2 protein in liver and kidney of rats. Overall, the results showed that MEPh can induce antioxidant and anti-apoptotic effects and also exerts beneficial effects for the treatment of Cd-induced hepatorenal toxicity.

The potential effect of berberine in mercury-induced hepatorenal toxicity in albino rats.

Mercury (Hg) is the third most dangerous heavy metal after arsenic and lead. Mercurys toxicity brings serious risks to health through negative pathological and biochemical effects. The study was designed to investigate the possible protective role of berberine (BN) in mercuric chloride (HgCl2) induced oxidative stress in hepatic and renal tissues. Adult male albino Wistar rats were exposed to mercuric chloride (HgCl2; 0.4 mg/kg bwt) for 7 days. Treatment with HgCl2 induced oxidative stress by increasing lipid peroxidation and nitric oxide production along with a concomitant decrease in glutathione and various antioxidant enzymes, namely superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. HgCl2 intoxication increased the activities of liver enzymes and the bilirubin level, in addition to the levels of urea and creatinine in serum. BN (100mg/kg bwt) treatment inhibited lipid peroxidation and nitric oxide production, whereas it increased glutathione content. Activities of antioxidants enzymes, superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, were also restored concomitantly when compared to control after BN administration. BN also inhibited the apoptotic effect of HgCl2 by increasing the expression of Bcl-2 protein in liver and kidney. Histopathological examination of the liver and kidney tissues proved the protective effect of BN against HgCl2 toxicity. These results demonstrated that BN augments antioxidant defense against HgCl2-induced toxicity and provides evidence that it has therapeutic potential as hepato- and reno-protective agent.

Oxidant/Antioxidant Imbalance and the Risk of Alzheimer's Disease

Alzheimers disease (AD) is the most common form of dementia characterized by progressive loss of memory and other cognitive functions among older people. Senile plaques and neurofibrillary tangles are the most hallmarks lesions in the brain of AD in addition to neurons loss. Accumulating evidence has shown that oxidative stress–induced damage may play an important role in the initiation and progression of AD pathogenesis. Redox impairment occurs when there is an imbalance between the production and quenching of free radicals from oxygen species. These reactive oxygen species augment the formation and aggregation of amyloid-β and tau protein hyperphosphorylation and vice versa. Currently, there is no available treatments can modify the disease. However, wide varieties of antioxidants show promise to delay or prevent the symptoms of AD and may help in treating the disease. In this review, the role of oxidative stress in AD pathogenesis and the common used antioxidant therapies for AD will summarize.Alzheimers disease (AD) is the most common form of dementia characterized by progressive loss of memory and other cognitive functions among older people. Senile plaques and neurofibrillary tangles are the most hallmarks lesions in the brain of AD in addition to neurons loss. Accumulating evidence has shown that oxidative stress-induced damage may play an important role in the initiation and progression of AD pathogenesis. Redox impairment occurs when there is an imbalance between the production and quenching of free radicals from oxygen species. These reactive oxygen species augment the formation and aggregation of amyloid-β and tau protein hyperphosphorylation and vice versa. Currently, there is no available treatments can modify the disease. However, wide varieties of antioxidants show promise to delay or prevent the symptoms of AD and may help in treating the disease. In this review, the role of oxidative stress in AD pathogenesis and the common used antioxidant therapies for AD will summarize.

The Potential Protective Effect of Physalis peruviana L. against Carbon Tetrachloride-Induced Hepatotoxicity in Rats Is Mediated by Suppression of Oxidative Stress and Downregulation of MMP-9 Expression

The active constituent profile in Cape gooseberry (Physalis peruviana L.) juice was determined by GC-MS. Quercetin and kaempferol were active components in the juice. In this study we have evaluated its potential protective effect on hepatic injury and fibrosis induced by carbon tetrachloride (CCl4). Twenty-eight rats divided into 4 groups: Group I served as control group, and Group II received weekly i.p. injection of 2 mL CCl4/kg bwt for 12 weeks. Group III were supplemented with Physalis juice via the drinking water. The animals of Group IV received Physalis juice as Group III and also were intraperitoneally injected weekly with 2 mL CCl4/kg bwt for 12 weeks. Hepatoprotective effect was evaluated by improvement in liver enzymes serum levels, reduction in collagen areas, downregulation in expression of the fibrotic marker MMP-9, reduction in the peroxidative marker malonaldehyde and the inflammatory marker nitric oxide, and restoration of the activity of antioxidant enzymatic and nonenzymatic systems, namely, glutathione content, superoxide dismutase, catalase, glutathione-S-transferase, glutathione peroxidase, and glutathione reductase activities. The results show that the potential hepatoprotective effects of Physalis peruviana may be due to physalis acts by promotion of processes that restore hepatolobular architecture and through the inhibition of oxidative stress pathway.

Indigofera oblongifolia Prevents Lead Acetate-Induced Hepatotoxicity, Oxidative Stress, Fibrosis and Apoptosis in Rats.

The current study was aimed to evaluate the preventive effects of Indigofera oblongifolia leaf extract (IOLE) on lead acetate (PbAc)-induced hepatotoxicity in adult male Wistar rats. PbAc was intraperitoneally injected at a dose of 20 mg/kg body weight for 5 days alone or in combination with the IOLE (100 mg/kg). Liver lead concentration and oxidative stress markers such as lipid peroxidation, hydrogen peroxide, nitric oxide, and glutathione content were investigated in addition to the enzymatic antioxidant activities. PbAc injection caused a significant elevation in the liver function parameters, lead level, lipid peroxidation, hydrogen peroxide, and nitric oxide, with a concomitant decline in the glutathione content compared with the control, accompanied by a significant inhibition of antioxidant enzyme activities. The induction of oxidative stress, lead accumulation, and histological alterations in the liver were successfully minimized by pre-administration of IOLE. In addition, the PbAc group showed increase in the levels of Bax, caspase-3, and matrix metalloproteinase-9 proteins, while the expression of Bcl-2 protein was decreased. Prior administration of IOLE significantly mitigated apoptosis and fibrosis in the liver. Finally, the major components in I. oblongifolia extract were identified as polyphenols, flavonoids, and organic acids using liquid chromatography coupled mass spectroscopy. Thus, the findings of the current study revealed that I. oblongifolia had protective, anti-fibrotic, antioxidant, and anti-apoptotic activities on PbAc-induced hepatotoxicity. The beneficial effects of I. oblongifolia were in part mediated by Nrf2/HO-1 pathway.

Antioxidant activities of Punica granatum (pomegranate) peel extract on brain of rats

Methanol extract of Punica granatum (pomegranate) peel was screened for its antioxidant activity on brain of adult male Wister albino rats. The antioxidant activity was determined by measuring reduced glutathione, catalase, superoxide dismutase, glutathione reductase, glutathione-S-transferase, and glutathione peroxidase. In addition, hydrogen peroxide (H2O2), nitric oxide (NO) and lipid peroxidation (MDA) were also measured in brain homogenate. Pomegranate peel treatment resulted in marked increase in most antioxidant parameters with reduction in oxidant H2O2, NO and MDA. On the basis of the previous results it can be concluded that pomegranate methanol peel extract is a promising natural product, which could be useful for the prevention of neurodegenerative diseases caused by oxidative stress.

Azadirachta indica Attenuates Cisplatin-Induced Nephrotoxicity and Oxidative Stress

We investigated the effects of methanolic leaves extract of Azadirachta indica (MLEN, 500 mg/kg bwt) on cisplatin- (CP-) induced nephrotoxicity and oxidative stress in rats. CP (5 mg/kg bwt) was injected intraperitoneally and MLEN was given by gastric gavage for 5 days before or after CP injection. After 5 days of CP injection, CP-induced injury of the renal tissue was evidenced (i) as histopathological damage of the renal tissue, (ii) as increases in serum uric acid, urea, and creatinine, (iii) as increases in malondialdehyde (MDA) and nitric oxide (NO), (iv) as decreases in the level of glutathione and activities of superoxide dismutase, catalase, glutathione reductase, glutathione-S-transferase, and glutathione peroxidase, and (v) as increase in the expression of nuclear factor kappa B and apoptosis in kidney tissues. However, the oral administration of MLEN to CP-intoxicated rats for 5 days brought back MDA, NO production, and enzymatic and nonenzymatic antioxidants to near normalcy. Moreover, the histological observations evidenced that neem extract effectively rescues the kidney from CP-mediated oxidative damage. Furthermore, PCR results for caspase-3 and caspase-9 and Bax genes showed downregulation in MLEN treated groups. Therefore, Azadirachta indica can be considered a potential candidate for protection of nephrotoxicity induced by cisplatin.

Melatonin protects rats from radiotherapy-induced small intestine toxicity

Radiotherapy-induced gut toxicity is among the most prevalent dose-limiting toxicities following radiotherapy. Prevention of radiation enteropathy requires protection of the small intestine. However, despite the prevalence and burden of this pathology, there are currently no effective treatments for radiotherapy-induced gut toxicity, and this pathology remains unclear. The present study aimed to investigate the changes induced in the rat small intestine after external irradiation of the tongue, and to explore the potential radio-protective effects of melatonin gel. Male Wistar rats were subjected to irradiation of their tongues with an X-Ray YXLON Y.Tu 320-D03 irradiator, receiving a dose of 7.5 Gy/day for 5 days. For 21 days post-irradiation, rats were treated with 45 mg/day melatonin gel or vehicle, by local application into their mouths. Our results showed that mitochondrial oxidative stress, bioenergetic impairment, and subsequent NLRP3 inflammasome activation were involved in the development of radiotherapy-induced gut toxicity. Oral treatment with melatonin gel had a protective effect in the small intestine, which was associated with mitochondrial protection and, consequently, with a reduced inflammatory response, blunting the NF-κB/NLRP3 inflammasome signaling activation. Thus, rats treated with melatonin gel showed reduced intestinal apoptosis, relieving mucosal dysfunction and facilitating intestinal mucosa recovery. Our findings suggest that oral treatment with melatonin gel may be a potential preventive therapy for radiotherapy-induced gut toxicity in cancer patients.