Study On The Protection Role Of Pananxatriol In Drug-induced Liver Injury

With exploration and combine use of new drugs, the rate of drug-induced liver injury (DILI) has increased every year and account for 9.5% of all adverse drug reactions (ADRs).DILI has become the second leading hepatic disease after virus hepatitis.It was reported that more than 1000 drugs are associated with hepatotoxicity. The most common drug that can induce liver injury is acetaminophen (APAP). APAP is a safe and effective analgesic or antipyretic drug when it is used at therapeutic concentrations.However, an acute or cumulative overdose can cause severe liver injury with the potential progress to liver failure. APAP hepatotoxicity is the leading cause of DILI. At present, the mechanisms on APAP-induced hepatocyte injury are still incompletely understood. Recent studies suggest that reactive metabolite formation, glutathione depletion, and alkylation of proteins, especially mitochondrial proteins, are critical initiating events for the toxicity.Reactive oxygen species (ROS) related oxidative-stress and calcium overload are likely to be the cause of APAP-induced hepatocyte injury.Thioredoxin (Trx) is an important redox protein in cells, with thioredoxin reductase and NADPH constitute the redox system.Trx can convert protein to the reduced form, scavenge harmful ROS, maintain the redox system. In addition, Trx can block the calcium channel, and inhibit apoptosis induced by calcium overload.In order to prevent the APAP-induced liver injury, more and more researches emphasize on exploring the Chinese herbs with liver-protective function, in addition to studies on changing the dosage forms of APAP and elucidating the mechanisms of APAP induced-liver injury. Panax notoginseng is rich in Yunnan, saponins are the main active component of Panax notoginseng, as high as 12%. Modern chemistry and pharmacology studies found extensive pharmacological effects of Panax notoginseng saponins (PNS), with anti-fatigue, decreasing blood sugar, promoting blood flow and dissolving blood stasis, improving immune function, treating inflammatory, increasing the ability of resisting hypoxia, scavenging ROS and resisting oxidant stresses. This study investigated the expression of Trx induced by PTS and the protective activity of panaxatriol (PTS) on APAP-induced liver injury in mice.The mice were treated with 100 mg/kg PTS for seven days, administered with 300 mg/kg APAP at the eighth day,24 hours later collect the serum and liver,using Western blot analyzed the expression of Trx, alanine aminotransferase (ALT) kit detected the serum enzyme of ALT, immunohistochemistry (IH) observed the histology changes, enzyme-linked immunosorbent assay (ELISA) detected TNF-a in serum.The results showed that PTS can significantly induced Trx overexpression,inhibit the serum enzyme of ALT increased,and protect hepatocyte to maintain normal morphology.This study suggested that PTS may protect the liver by inducing Trx overexpression, and provided the basic theoretical foundation for elucidating mechanism on PTS and Trx protecting liver.