Effect of Grape Seeds (Vitis vinifera L.) and Mandarin Peels (Citrus reticulate L.) Extracts on the Cardiotoxicity Induced by Cyclophosphamide in Rats

Abstract

The current study was developed to investigate the influence of grape seeds (GS) and mandarin peels (MP) extracts as a powerful antioxidants on the cardiotoxicity induced by cyclophosphamide (CP) in rats. Sixty adult male Sprague-Dawley rats were divided into 6 groups. Group (1) (Control group): Rats were received distilled water (2.5 ml / kg BW) daily by oral intubation for 6 weeks and injected intraperitoneally (i.p) with saline (0.9 %) as single dose at the end of the sixth week of the experiment. Group (2): Rats were received distilled water and injected with single dose of cyclophosphamide which dissolved in saline (200 mg/kg BW. i.p.) at the end of the sixth week of the experiment. Groups (3 and 4): Rats were received grape seeds extracts low and high doses (150 and 300 mg /kg BW), respectively daily by oral intubation for 6 weeks then injected with cyclophosphamide as group 2. Groups (5 and 6): Rats were received mandarin peels extracts low and high doses (150 and 300 mg /kg BW), respectively daily for 6 weeks then injected with cyclophosphamide as group 2. The results of this study documented that CP caused a significant increase in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALK-P), creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), creatine kinase (CK) enzymes activities and serum malondialdehyde (MDA) level. While total antioxidant capacity level (TAC) showed a significant decrease. On the other hand cardiac catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities and cardiac β cell lymphoma-2 (Bcl-2) level showed a significant decrease in CP intoxicated group while cardiac p53, caspase-3 and DNA fragmentation levels showed a significant increase in CP intoxicated group. Also, some histopathological changes were observed in liver and heart tissues in CP group. Oral administration of GS and MP caused an ameliorative effect in oxidative and apoptotic biomarkers, liver and heart function enzymes activities with an improvement of histopathological changes in liver and heart tissues. Conclusion: Our data proved that the protective effect of grape seeds and mandarin peels in cyclophosphamide intoxicated group may be due to their antioxidant, anti-inflammatory and anti- apoptotic properties.