Hepatoprotective Effects of Rubus idaeus L. Leaves against CCl4-Induced Liver Injury via Antioxidant, Anti-inflammatory and Antiapoptotic Mechanisms

Abstract

Aims: To investigate the hepatoprotective effects of red raspberry (Rubus idaeus L.) leaves against oxidative stress, inflammation and apoptosis induced by carbon tetrachloride (CCl4) in rats. Study Design and Methodology: Forty rats were divided into 5 groups, 1) normal control; 2) Raspberry (Rsp) control (100 mg/kg); 3) CCl4 control; 4) and 5) CCl4 groups pre-treated with 50 and 100 mg/kg of Rsp leaves, respectively, once daily for 10 days.  Liver injury was induced on the 11th day in groups 3, 4 and 5 by intraperitoneal injection of CCl4 (1.0 ml/kg) in 50% olive oil (1:1). Serum and liver were separated and prepared for biochemical and histological assay. Antioxidant, inflammatory and apoptotic markers were evaluated. Results: CCl4-induced liver damage was manifested by increased activities of serum marker enzymes, elevated levels of lipid peroxidation and by decreased hepatic antioxidants including reduced glutathione, glutathione peroxidase, superoxide dismutase and catalase. CCl4 also resulted in elevated levels of hepatic inflammatory mediators including tumor necrosis factor-α (TNF- α), interleukin -6 (IL-6), IL-1β and nitric oxide (NO) as well as upregulation of apoptotic markers including caspase-3, FasL and Bax. Hepatic levels of Bcl2, an anti-apoptotic factor, was decreased by CCl4. Pretreatment with Rsp leaves significantly ameliorated the elevation in serum liver enzymes and prevented lipid peroxidation and the depletion of the antioxidants. In addition, Rsp leaves exhibited anti-inflammatory effects via attenuation of increased hepatic levels of TNF-α, Il-6, IL-1β and NO. Additionally, CCl4-Induced apoptosis in the liver cell was attenuated by Rsp pretreatment. With regard to histological examination, Rsp leaves significantly alleviated degeneration and necrosis of hepatocytes, accompanied by decreased inflammatory cell infiltration. Conclusion: These results suggest that Rsp leaves have protective effects against CCl4-induced acute liver injury, and this protection is likely due to antioxidant, anti-inflammatory and anti-apoptotic mechanisms.