Glucose-6-phosphate Dehydrogenase Activity During Nʹ-nitrosodiethylamine-induced Hepatic Damage

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 Nʹ-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.