IJST (2015) 39A1: 17-23 Iranian Journal of Science & Technology http://ijsts.shirazu.ac.ir Berberine improves liver injury following renal ischemia reperfusion in rats F. Gholampour 1 *, F. Karimifard 1 and S. M. Owji 2 1 Department of Biology, School of Sciences, Shiraz University, Shiraz, Iran 2 Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran E-mail: gholampour@shirazu.ac.ir Abstract This study investigated the effect of berberine on the hepatic dysfunction and histological damage induced by renal ischaemia/ reperfusion (I/R) at an early stage. There were four groups (n=7). In Ber+I/R group, rats received berberine (Ber; 15 mg/kg/day) orally for 7 days before induction of ischemia. I/R group received distilled water orally for 7 days. In sham and Ber+sham groups in which arteries were not occluded, distilled water and berberin (15 mg/kg/day) respectively were administered orally for 7 days before surgery. Renal ischemia was induced by occlusion of both renal arteries for 45 min followed by 24 h of reperfusion. Blood samples were collected for biochemical analysis, and finally liver samples were preserved for future histological examination. The renal ischaemic challenge resulted in major histological damage of the liver, which was associated with increased levels of creatinine, blood urea nitrogen (BUN), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and alkaline phosphatase (ALK) during reperfusion period. In Ber+I/R group, the histological damage to the liver was improved along with increase in plasma creatinine, BUN, ALT, AST, LDH and ALK being smaller than those of the non-treated rats. Berberine exhibited a hepatoameliorative effect against renal ischemia/reperfusion-induced lesions. Keywords: Berberine; Renal ischaemia/reperfusion; liver; Alanine aminotransferase; Aspartate aminotransferase; Lactate dehydrogenase 1. Introduction Renal ischemia/reperfusion (I/R) injury is the major cause of acute renal failure in both native and transplanted kidneys (Kelly and Molitoris, 2000). Inflammation contributes to renal I/R injury, potentially causing renal dysfunction. One of the main constituents of the inflammatory infiltrate are neutrophils, which are deleterious for the renal tissue (Rouschop et al. 2005). Although reperfusion is essential for the survival of ischemic tissue, there is evidence that reperfusion itself causes additional cellular injury (Weight et al. 1996). Massive influx of neutrophils mediates the development of postischemic renal failure through the release of cytotoxic proteases and oxygen-derived radicals (Rouschop et al. 2005). In the kidney, inflammatory process is initiated by both endothelial and tubular cell dysfunction. A number of different proinflammatory cytokines, such as IL-1, -6, and -8, TGF-β, and TNF-α, are released into the renal tissue and finally in the circulation (Kielar et al. 2005; Ramesh and Reeves, 2004). According to Park et al. (2011) ischemic *Corresponding author Received: 2 November 2013 / Accepted: 5 July 2014 renal injury initiates IL-17A generation in the small intestine resulting in the small intestinal and liver inflammation, apoptosis and necrosis. In modern system of medicine, valuable drugs are not available to safeguard the liver against various damages (Pattanayak et al. 2011). Thus, the hepatoprotective activity of plants were explored using a variety of toxicants in experimental animals. Generally, some bioactive compounds found in plants were responsible for protecting the cells from oxidative stress via prevention or detoxification of free radicals and helped to prevent various disfunctions. Berberine, an alkaloid isolated from rhizomes, roots, and stem bulk of the plants such as the Berberidaceae family has gained much attention in recent years for its anti-inflammatory, antioxidant, anticancer, antiviral, and antibacterial activities (Imanshahidi and Hosseinzadeh 2008; Kuo et al. 2004; Kettmann et al. 2004; Stermitz et al. 2000; Racková et al. 2003; Iwasa et al. 1996; Erdogan et al. 2006). This research evaluated the possible therapeutic potential of berberine as a preventive agent in hepatic damages induced by ischemic acute renal failure in rats.