Fullerene C60 nanoparticles ameliorated cyclophosphamide-induced acute hepatotoxicity in rats.

Cyclophosphamide (CP), a chemotherapeutic agent, induces hepatotoxicity as one of its side effects. Therefore, the aim of the present study is to investigate the potential hepatoprotective effects of fullerene C60 nanoparticles (C60) against the high toxic dose of CP. Twenty five albino rats were randomly assigned to 5 groups (n=5 per group). Group 1 served as a control. Group 2 received 200mg/kg of CP once intraperitoneally, while group 3 treated with the same CP dose plus C60 (4mgkg, orally) daily for 10days. Group 4 exposed CP and ZnCl2 (4mgkg, orally) daily for 10days. Group 5 exposed to CP and co-treated with C60 and ZnCl2. One day after last treatment, blood and livers were collected for hematological, biochemical and histopathological investigations. C60 normalized significantly RBCs, HB, PCV, WBCs and platelets numbers compared to CP-exposed rats. Moreover, liver enzymes namely ALT, AST and ALP revealed that CP elevated their levels and C60 significantly (p<0.05) reduced them to basal levels. The level of oxidative stress marker namely, MDA was elevated upon CP exposure and normalized by C60 treatment. In addition, antioxidant systems e.g. GSH, CAT and SOD were depleted from liver tissue due to CP toxicity these were recovered by C60 administration. The hepatoprotective effects of C60 on tested parameters were comparable with ZnCl2 and neither additive nor synergistic effect was observed. Histopathogically, severe liver degeneration was recorded after CP treatment, however, only mild changes were observed after C60 administration. Our data suggest that C60 improves both blood and hepatic parameters altered by cyclophosphamide-induced toxicities. The current study is of clinical relevance particularly, application of C60 as a monotherapy or in combination to ameliorate the CP side effects in cancer-treated patients.

Oxidative stress and some biochemical alterations due to scorpion (Leiurus quinquestriatus) crude venom in rats.

Scorpion envenomation is a common medical problem in many countries; it is an important cause of morbidity and mortality. The venom of Leiurus quinquestriatus (LQ) is responsible for a number of deaths in children and adults. It has been stated that specific pathophysiological conditions such as generation of oxygen free radicals may trigger the onset of multiple organ dysfunction; therefore, the present study aimed to assess the oxidative stress mediated by LQ crude venom and its effect on the biochemical parameters in rats. Adult male Albino rats (250±30g body weight) were divided into three groups (n=5). In control group, rats were intraperitoneally (ip) injected with 50µL saline solution. Groups 2 and 3 were ip injected with 0.1mg/kg and 0.2mg/kg body weight of crude venom, respectively. Blood samples and liver tissues were harvested 1, 2 and 4h post-injection. Serum levels of glucose, cholesterol, creatinine, urea, uric acid and malondialdehyde increased significantly in envenomed animals within 1, 2 and 4h post-injection, compared to controls. However, the levels of total serum protein, albumin, globulin and triglycerides as well as catalase, glutathione peroxidase and super oxide dismutase in envenomed rats were significantly decreased compared to controls. We can conclude that LQ crude venom induces oxidative stress via reduction of antioxidant systems and alters some biochemical parameters of envenomed rats.

Effect of a bradykinin-potentiating factor isolated from scorpion venom (Leiurus quinquestriatus) on some blood indices and lipid profile in irradiated rats.

Bradykinin appears to be an important regulator of cardiovascular function. It is also being increasingly noted as a participant in actions of drugs that affect the liver, kidney, and circulation. In our previous studies, bradykinin-potentiating factor (BPF) isolated from scorpion venom (Leiurus quinquestriatus) has been shown to be protective against hepato- and nephrotoxicity as well as healing skin burns by reducing oxidative stress in hyperglycemic conditions. Therefore, we aim to evaluate the ability of BPF in treating irradiated rats. A group of rats was exposed to γ-irradiation and subsequently treated with BPF injections aiming to elucidate the possibility of BPF to rescue γ-irradiation harmful effects. As controls, we used γ-irradiation exposed, BPF-injected, and untreated rats. The data obtained showed that the irradiated animals suffered from marked changes of many important blood parameters including red blood cells, leukocytes, platelets, hemoglobin, packed cell volume, high-density cholesterol, total cholesterol, triglycerides, and low-density cholesterol. Interestingly, BPF was able to rescue the deleterious effects of irradiation in rats and normalized their blood parameters to the basal levels. We conclude that BPF could ameliorate irradiation damaging effects.

Hepato- and nephroprotective effects of bradykinin potentiating factor from scorpion (Buthus occitanus) venom on mercuric chloride-treated rats.

Bioactive peptides such as bradykinin potentiating factor (BPF), have, anti-oxidative, anti-inflammatory, immunomodulatory and ameliorative effects in chronic diseases and play a potential role in cancer prevention. It is known that the liver and kidney accumulate inorganic mercury upon exposure, which often leads to mercury intoxication in these organs. In this study, we investigated the effect of bradykinin potentiating factor (BPF), a scorpion venom peptide, on mercuric chloride-induced hepatic and renal toxicity in rats. We used 20 adult male Albino rats divided into four equal groups: the first group was injected with saline (control); the second group was administered daily with mercuric chloride (HgCl2) for 2 weeks; the third group was administered with BPF twice weekly for 2 successive weeks, while the fourth group was exposed to BPF followed by HgCl2. We observed that HgCl2 treated rats had a significant increase in serum ALT, AST, ALP, creatinine and urea levels compared to control. Furthermore, HgCl2 treated rats showed a marked decrease in total proteins, albumin and uric acids compared to control. The previously studied parameters were not significantly changed in BPF pretreated rats compared to control. Moreover, a significant decrease in the activities of glutathione perioxidase (GSH), superoxide dismutase (SOD), and catalase (CAT), in addition to a significant increase in the level of malondialdehyde (MDA) were observed in hepatic and renal tissues of rats after HgCl2 treatment. In contrast, the HgCl2/BPF treated rats showed a significant elevation in the activity of GSH, SOD, and CAT accompanied with a significant regression in the level of MDA compared to the HgCl2 exposed rats. We conclude that treatment with BPF is a promising prophylactic approach for the management of mercuric chloride-induced hepato- and nephro-toxicities.

Prevention of hepatic and renal toxicity with bradykinin potentiating factor (BPF) isolated from Egyptian scorpion venom (Buthus occitanus) in gentamicin treated rats.

The present investigation report the effect of a bradykinin-potentiating factor (BPF) on gentamicin-induced oxidative stress in rat liver and kidney. BPF is a peptide fraction isolated from the venom of the Egyptian scorpion (Buthus occitanus) has been demonstrated to have antioxidant, free radical scavenger and anti-inflammatory effects. Thirty male Rattus norvegicus (130-150 g) were included and divided into three equal groups as follows: Group I (control), group II was (ip) injected with gentamicin alone (80 mg/kg/day) for 15 days, group III was given (ip) injection of BPF (1mg/kg/day) one hour prior to gentamicin treatment for 15 days with the same dose of gentamicin as group II. Both organs were subjected to histopathological analysis with the light microscope. The activities of alanine aminotransferase (ALT), asparate aminotransferase (AST) and alkaline phosphatase (ALP) in serum were measured as indicators of the liver function. As parameters of the kidney function, creatinine, uric acid and urea concentrations were determined. Also, malondialdehyde (MDA), reduced glutathione (GSH), super oxide dismutase (SOD) and catalase (CAT) were determined in both tissues. Gentamicin caused a significant decrease or inhibition in the activities of GSH, SOD, and CAT, with significant increase in the level of MDA, ALT, AST, ALP, as well as creatinine, uric acid and urea concentrations in versus to control groups in both liver and kidney. Co-administration of gentamicin and BPF significantly increased the activity of GSH, SOD, and CAT, with significant decrease in the level of MDA and maintained serum (ALT); (AST); (ALP), creatinine, uric acid and urea concentrations as the same level as control group. Moreover, administration of gentamicin resulted in damage to liver and kidney structures. Administration of BPF before gentamicin exposure prevented severe alterations of biochemical parameters and disruptions of liver and kidney structures. In conclusion, this study obviously demonstrated that pretreatment with BPF significantly attenuated the physiological and histopathological alterations induced by gentamicin. Also, the present study identifies new areas of research for development of better therapeutic agents for liver, kidney, and other organs dysfunctions and diseases.