Cardioprotective effect of grape-seed proanthocyanidins on doxorubicin-induced cardiac toxicity in rats.

CONTEXT: Doxorubicin (Dox) is an anthracycline antibiotic used as anticancer agent. However, its use is limited due to its cardiotoxicity which is mainly attributed to accumulation of reactive oxygen species. OBJECTIVE: This study was conducted to assess whether the antioxidant, proanthocyanidins (Pro) can ameliorate Dox-induced cardiotoxicity in rats. MATERIALS AND METHODS: Male Sprague-Dawely rats were divided into four groups. Group I was control. Group II received Pro (70 mg/kg, orally) once daily for 10 days. Group III received doxorubicin 15 mg/kg i.p. as a single dose on the 7th day and Group IV animals were treated with Pro once daily for 10 days and Dox on the 7th day. The parameters of study were serum biomarkers, cardiac tissue antioxidant status, ECG, and effect on aconitine-induced cardiotoxicity. RESULTS: Cardiac toxicity of doxorubicin was manifested as a significant increase in heart rate, elevation of the ST segment, prolongation of the QT interval and an increase in T wave amplitude. In addition, Dox enhanced aconitine-induced cardiotoxicity by a significant decrease in the aconitine dose producing ventricular tachycardia (VT). Administration of Pro significantly suppressed Dox-induced ECG changes and normalized the aconitine dose producing VT. The toxicity of Dox was also confirmed biochemically by significant elevation of serum CK-MB and LDH activities as well as myocardial MDA and GSH contents and decrease in serum catalase and myocardial SOD activities. Administration of Pro significantly suppressed these biochemical changes. DISCUSSION AND CONCLUSION: These results suggest that proanthocyanidins might be a potential cardioprotective agent against Dox-induced cardiotoxicity due to its antioxidant properties.

Prevention and treatment of Schistosoma mansoni-induced liver fibrosis in mice.

The present study was designed to examine the potential preventive and curative effects of curcumin, resveratrol, imatinib, rosiglitazone, losartan and bosentan (BOS) on Schistosoma mansoni-induced liver fibrosis in mice. Induction of liver fibrosis was produced in male Swiss mice by subcutaneous injection of S. mansoni cercariae per mouse. Mice were left for 28 days before starting the experiment then mice were divided into two main groups. The first group was further subdivided into experimental groups and started drug treatment at day 28 after infection and continued for 2 weeks in order to evaluate the potential preventive effects of the mentioned drugs on S. mansoni-induced liver fibrosis. The second group of mice were left for 2 weeks and then treated with praziquantel for two consecutive days to eradicate the worms and so stop egg disposition and further fibrosis development. Mice were then subdivided into the experimental groups and drug treatment was started for 2 weeks to evaluate their efficacy to decrease the developed fibrosis. At the end of the experiment period, mice were killed and serum was collected for the estimation of alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin and albumin. Liver tissue was taken for the estimation of hepatic hydroxyproline content and histopathological examination to confirm the biochemical results. Results of the study indicate that curcumin and imatinib have potent antifibrotic activity both in suppressing and reversing S. mansoni-induced liver fibrosis, while resveratrol has beneficial effects only in suppressing the development of S. mansoni-induced liver fibrosis.