Picroliv preconditioning protects the rat liver against ischemia-reperfusion injury

Cell death following ischemia-reperfusion injury is a major concern in clin ical issues such as organ transplantation and trauma. The need to identify agents with a potential for preventing such damage has assumed great import ance. We have evaluated the efficacy of picroliv, a potent antioxidant deri ved from the plant Picrorhiza kurrooa, in protecting against hepatic ischem ia-reperfusion injury in vivo. Picroliv was fed to male Sprague Dawley rats in a dose of 12 mg/kg once daily by oral gavage for 7 days prior to hepati c ischemia. Ischemia was induced by occluding the hepatic pedicel with a mi croaneurysm clip for 30 min and reperfusion was allowed thereafter for vary ing period (15-120 min) by releasing the microaneurysm clip. Picroliv pretr eatment resulted in better hepatocyte glycogen preservation and reduced apo ptosis. Reduction in apoptosis was associated with decreased mRNA expressio n of caspase-3 and Fas. Oxidant induced cellular damage as measured by tiss ue malondialdehyde (MDA) levels was significantly less following picroliv p retreatment. Both a reduction in neutrophil infiltration and an increased l evel of intracellular antioxidant enzyme superoxide dismutase possibly cont ributed to the reduction in tissue lipid peroxidation. Tissue inflammatory cytokines level of interleukin-1 alpha. (IL-alpha) and interleukin-1 beta ( IL-1 beta) was also lower in picroliv group. Furthermore, picroliv pretreat ment resulted in enhanced proliferating cell nuclear antigen (PCNA) immunor eactivity. These studies strongly suggest picroliv to be a promising agent for ameliorating injury following ischemia-reperfusion. (C) 2000 Elsevier S cience B.V. All rights reserved.