Glucose-6-phosphate Dehydrogenase Activity During N?-nitrosodiethylamine-induced Hepatic Damage

摘要

Abstract Glucose-6-phosphate dehydrogenase (G6PD), a key regulatory enzyme of the pentose phosphate pathway, catalyses the first rate-limiting reaction to produce ribose-5-phosphate for nucleic acid synthesis and {NADPH} to use in reductive biosynthesis. The available studies indicate an antioxidant role for {G6PD} and variation in its levels as a result of cellular insult. In this study, the activity of {G6PD} was monitored during N?-nitrosodiethylamine (NDEA)-induced hepatic damage in Wistar rats. {NDEA} generates hepatotoxicity and possesses mutagenic effects. To induce hepatic damage, {NDEA} was administered at doses of 100 mg kg? 1 body weight week? 1 (i.p.) for 14 days. The animals of the control and treated groups were sacrificed each week. The extent of liver damage was ensured by {LFT} biomarkers, such as transaminases, ALP, bilirubin and the hepato-somatic index (HSI) along with histopathological observations of H&E and Masson's trichrome stained liver specimens. The results of the present study show that at the selected doses, {NDEA} significantly elevates {LFT} proteins and bilirubin and damages the lobular architecture in a dose-dependent manner. Software analysis of zymograms indicates maximum activity of the hepatic {G6PD} levels in day-14 NDEA-treated animals. Our spectrophotometry data further support the above findings on hepatic {G6PD} levels and demonstrate an approximately 1.63 × and 1.66 × fold increase in day-7 and day-14 {NDEA} intoxicated animals (P < 0.05). It is concluded that elevation in the {G6PD} activity is apparently the consequence of NDEA-induced intoxication or oxidative stress, leading to hepatic damage to provide sufficient {NADPH} for microsomal detoxification and ribose-5-phosphate for {DNA} synthesis and repair, respectively, to maintain the cellular redox status.