The potential protective role of grape seed proanthocyanidin extract against the mixture of carboplatin and thalidomide -induced hepatotoxicity and cardiotoxicity in male rats

Abstract

Thalidomide is used experimentally to treat various cancers, also carboplatin is a chemotherapy drug used against some forms of cancer. Grape Seed Proanthocyanidin Extract (GSPE) has an enormously beneficial role in overcoming the adverse effects of chemotherapeutic agents due to its excellent antioxidant properties. Animals were divided into four groups as follows: The first group was used as control, the second group were treated orally for 28 consecutive days with GSPE (200 mg/ kg BW), the third group were treated intraperitoneally (i.p) with thalidomide (60 mg/kg BW) for 14 consecutive days then followed by carboplatin (196 mg/kg BW) for another 14 days and the animals of the fourth group were treated with the combination of GSPE (200 mg/kg BW) and thalidomide (60 mg/kg BW) for 14-day and then followed by GSPE (200 mg/kg BW) and carboplatin (196 mg/kg BW) for other 14-day. Inflammatory cytokines, P53, oxidative stress markers, biochemical parameters, and histological analysis measured. Carboplatin and thalidomide caused oxidative stress via the elevation in free radicals and nitric oxide and the reduction in the antioxidant enzymes and glutathione in liver and heart. Tumor suppressor gene P53, tumor necrosis factor-α, and interleukin-6 were significantly increased in liver and heart. Thalidomide and carboplatin caused biochemical and histological changes in the liver and heart. Grape seed proanthocyanidin extract reduced carboplatin and thalidomide -induced liver and heart injury throughout its potent antioxidant activity. In conclusion, carboplatin and thalidomide caused hepatotoxicity and cardiotoxicity and grape seed proanthocyanidin extract showed hepatic and cardiac protective effects due to its antioxidant and anti-inflammatory potentials. *Correspondence to: Heba Mohamed Abdou, Department of Zoology, Faculty of Science, Alexandria University, Egypt, Tel:+203-3921595; E-mail: dr.heba_ abdou3000@yahoo.com