Protective effect of ethanolic extract of Crocus sativus L. [Saffron] stigma against Cisplatin induced hepatotoxicity in rats

Cisplatin, as an important anti-cancer drug, is a potent hepatotoxicant. The aim of the present study was to evaluate the protective effect of ethanolic extract of Crocus sativus L. stigma [EECSL.S] against cisplatin-induced hepatotoxicity in the rats. 40 male Wistar rats were randomly allocated into 5 groups [1-Normal control, 2- Toxicant control, 3-Positive control and 4 and 5- Treatment with extract] of 8 animals each. Cisplatin was injected [0.4 mg/kg] to groups 2-4 daily for 8 weeks, intraperitoneally. Simultaneously, normal saline [10 ml/kg] for groups 1 and 2, silymarin [50 mg/kg] for group 3 and EECSL.S [40 and 80 mg/kg] for groups 4 and 5 were administered through the gavage. At the end of experiment, levels of serum biomarkers of hepatic injury as well as antioxidant activity in liver homogenates of the rats were assessed. Moreover, histopathological observation was assayed at the degree of hepatic injury. In the cisplatin receiving rats, EECSL.S [40 and 80 mg/kg] and silymarin significantly decreased the levels of serum biomarkers of hepatic injury and total bilirubin and significantly elevated the levels of serum albumin and total proteins. In these rats, EECSL.S and silymarin decreased the lipid peroxidation and elevated the levels of antioxidant enzymes in a dose dependent manner. Histopathologically, EECSL.S and silymarin ameliorated cisplatin-induced hepatic injuries and the changes were in agreement with biochemical findings. EECSL.S protects hepatic tissue against cisplatin-induced hepatotoxicity in rats due to its anti-oxidant properties

Ambivalent effects of atorvastatin on angiogenesis, epidermal cell proliferation and tumorgenesis in animal models

A growing body of preclinical data indicates that statins may possess antineoplastic properties; however, some studies have raised the possibility that statins may also have carcinogenic potential. An air pouch model was used for angiogenesis. Single or multiple applications of croton oil on the back of Swiss albino mice with or without initiation by dimethylbenz[a]antheracene [DMBA] were used to evaluate the skin tumorgenesis, ultrastructural and histological alterations. Atorvastatin [orally, 10 mg/kg/day] produced a significant [P<0.05] reduction in angiogenesis. Concurrent administration of mevalonate reversed the antiangiogenic effect of atorvastatin. However, local injection of atorvastatin [200 micro g] into the pouches induced a significant [P<0.5] increase in angiogenesis that was not reversed by co-administration of mevalonate. The disturbance of cell polarity, inflammatory response, thickness of epidermal layer, and mitotic index induced by croton oil were inhibited markedly and dose-dependently [P<0.001] by pre-treatment with atorvastatin. In spite of the strong anti-inflammatory and anti-proliferative effects of atorvastatin on epidermal cell proliferation, it was identified that the same doses of atorvastatin in DMBA-initiated and croton oil-promoted skin tumorgenesis in mice increased the incidence of tumors and their conversion into malignant carcinoma. The reasons for these discrepancies remain unclear, and could be related to ambivalent effects of atorvastatin on angiogenesis or to specific differences in the experimental conditions. It is suggested that the pro-angiogenic effect of the drug, which could be responsible for promotion of skin tumors, is independent of the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibition that can be mediated directly by atorvastatin

[Effect of grape seed extract on cardiomyocyte apoptosis in streptozotocin induced diabetic rats]

Background: Apoptosis is a regulated, energy-dependent, cell suicide mechanism that has also been reported to play a critical role in the development of diabetic cardiomyopathy. In the present study, the effect of grape seed extract on cardiomyocyte apoptosis status in streptozotocin induced diabetic rats was investigated

Materials and methods: 40 male wistar rats with age of 12 weeks and 200-300g weight were randomly allocated into four equal groups namely normal vehicle treated rats, healthy rats received 40 mg/kg grape seed extract, diabetic rats and diabetic rats treated with grape seed extract [40 mg/kg] for 12 weeks. Diabetes was induced by a single intraperitoneal injection of STZ [50 mg/kg] in diabetic groups

Results: Significant increase of apoptotic cells was noted in diabetic rats. Oral administration of grape seed extract resulted in significant reduction of cardiomyocyte apoptosis in diabetic rats

Conclusion: These results provide confirmatory evidence of apoptosis in diabetes and point towards the possible anti-apoptotic effect of grape seed extract

[ effects of pentoxifylline on renal apoptosis following ischemic reperfusion injury in rats]

Ischemia-reperfusion induces cell death and inflammatory reaction. It is a common clinical problem associated with acute renal failure and renal transplantation. In this study, the effects of pentoxifylline on rat kidney function and cell injury after ischemia-reperfusion were evaluated. In this experimental study, 20 male wistar rats with mean weight of 250-300g were assigned randomly into control and treatment groups [each group 10 rats]. In control group, celiotomy was performed by ventral midline incision. The left kidney was isolated, and then both the renal artery and vein were clamped. After 60 minutes of warm ischemia, the vessels were unclamped and the right kidney was removed. 72 hours after reperfusion, tissue samples from the left kidney were taken for histopathologic examination after death. The same procedures were repeated in the treatment group after administration of 45mg/kg/PO pentoxifylline, 3 hours before surgery. This treatment was continued every 12h until death. Apoptotic changes were compared between two groups by Mann-Whitney U test. Statistical significance was considered at p<0.05. The treatment group showed lower levels of cell death than the control group [P<0.05]. Pentoxifylline alone might play a role in attenuation of renal ischemia-reperfusion injury and Apoptosis

Effects of age progression on apoptosis of ventricular cardiomyocyte of rats

Increased oxidative stress with increasing age is a source of damage to cellular structure and function. Tissue with few or no cell divisions, such as heart is theoretically more susceptible to accumulative damage caused by oxidative stress. The purpose of this study was to investigate the effect of age progression on apoptosis rate of rat hearts. In this experimental study, Forty eight male Wistar rats [three months old and body mass of 230 +/- 14 g] were randomly assigned to four groups, 6, 9, 12 and 15 months of age. Six hearts of each group were assigned to apoptosis analysis by TUNEL method and fixed in 10% formalin. Six remaining hearts of each group were washed out and homogenized in ice cold buffer and the supernatant were assigned to apoptosis analysis by ELISA method. The results of TUNEL and ELISA apoptosis detection showed that the rates of apoptosis were increased with age in 12 and 15 months groups compared to 6 months rats [p<0.05 and p<0.01, respectively]. Moreover the results of TUNEL method depicts a significant increase in apoptosis rate in 9 months group compared to 6 months group [p<0.05]. These results suggest that the age of animals might be important factor in the increase of the heart apoptosis rate

[Study of apoptosis induced by calendula officinalis extract on experimental colon carcinoma in rats]

In vitro studies have demonstrated the anticancer effect of Calendula officinalis extract on tumor cell line derived from colorectal cancers. The inhibition ranged from 70-100%. The aim of this study was to evaluate the apoptosis in epiththelial displastic colon cells following treated with Calendula officinalis extract. In this experimental study, 56 wistar male rats with age of 12 weeks and 200-300g weight were allocated into two equal groups of treatment and control. For induction of colorectal carcinoma, these two groups were given 1, 2-dimethylhydrazine [40mg/kg], as subcutaneous injection, twice a week for two weeks. Treatment group also was treated with Calendula officinalis extract [200mg/kg/day] orally for 10 weeks. After 10 weeks, distal parts of colon tissue were biopsied in both groups and 3-4 micron tissue section was prepared through TUNEL staining method. Immunohistopathological study reveals that apoptotic cells of displastic colon epithelial cells in treatment group were higher than control group. Mean difference between treatment and control groups were statistically significant [p<0.01]. This study indicated that Calendula officinalis extract would be induced apoptosis of displastic colon cells in experimental colorectal carcinoma of rats