PROTECTIVE EFFECTS OF GRAPE SEED EXTRACT (VITIS VINIFERA) AGAINST CISPLATIN-INDUCED LIVER DAMAGE IN RABBITS. (HISTOLOGICAL AND HISTOPATHOLOGICAL STUDY)

Abstract

Cisplatin is a chemotherapeutic drug used in the treatment of various cancer types. It can be considered a double-edged sword. It is a potent anticancer agent at the same time has toxic effect on various tissues as it causes hepatotoxicity. It was determined to cause liver toxicity and to weaken the antioxidant defense systems in liver. A decrease in antioxidant enzymes resulted from cisplatin induced tissue toxicity. Moreover, the development of therapies to prevent the appearance of cisplatin- induced tissue toxicities has focused on administration of antioxidants along with cisplatin treatment. The grape seeds exhibit a broad spectrum of pharmacological properties against oxidative stress. Therefore, the aim of present study was designed to investigate the protective effects of grape seed extract on the liver damage in cisplatin treated rabbits. Twenty seven healthy rabbits of local mixed breed were selected, divided into three equal groups, the first group (CON group) served as control and received a single intraperitoneal injection of normal saline solution once per week for 6 weeks; the second group (CIS group) were treated with therapeutic dose of cisplatin intraperitoneally once per week for six weeks; the third group (CIS+GSE group) served as protective group and was concomitantly treated with grape seeds extract by oral gavages and cisplatin injection intraperitoneally once per week for six successive weeks. Administration of grape seeds extract by oral gavages starting from the first day of the experiment for 6 consecutive days before and 6 consecutive days after the cisplatin injection and continued daily for 6 weeks. The histopathological findings present in current study showed that cisplatin toxicity produced significant structural changes in the liver of CIS group, cisplatin treated group, in the form of prominent disorganized architecture and loss of liver lobulation, distortion of the arrangement of parenchyma of the liver, loss of radial arrangement of sinusoids from the central vein of the liver, Dilatation and congestion of central veins, sinusoids and portal traids, degenerative changes in hepatocytes and pyknotic nuclei indicating necrosis. Marked vacuolar degeneration mainly hydropic ballooning degeneration and hyper activation of Kupffer cells and inflammatory cellular infiltrations were also observed. This finding reflected the cytotoxic effects of cisplatin in hepatic tissue. While, in the sections from the liver of animals received therapeutic dose of cisplatin and treated by grape seed extract, group (CIS+GSE) clearly showed that there was a significant alleviated hepatotoxicity, since histopathological changes were markedly less pronounced compared to animals treated with cisplatin alone. Therefore, and based on our findings, the grape seed extract contributes significantly to the improvement of histological alterations in rabbit liver caused by cisplatin.