Chronotherapeutic effect of morin in experimental chronic hyperammonemic rats

Abstract

Aim: Ammonia is a neurotoxin that has been strongly implicated in the pathogenesis of hepatic encephalopathy and a major pathogenic factor associated with inborn errors of urea cycle. In this present work we aimed to evaluate the chronotherapeutic effect of morin (3,5,7,2',4'-pentahydroxyflavone), a plant component, on ammonium chloride (AC) (100 mg/kg; intraperitoneal)-induced hyperammonemia in Wistar rats (180-200 g). Materials, Methods and Results: Morin (30 mg/kg body weight) was administered to rats at 06:00, 12:00, 18:00, and 24:00 hours in hyperammonemia. The influence of morin on AC-induced hyperammonemia at different time points (06:00, 12:00, 18:00, and 24:00 hours) was evaluated by analyzing the circulatory levels of ammonia; urea; thiobarbituric acid reactive substances (TBARS); hydroperoxides (HP); liver markers [alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP)]; glutathione peroxidase (GPx); superoxide dismutase (SOD); catalase (CAT); reduced glutathione (GSH); and vitamins A, C, and E. The levels of these components were significantly elevated in AC-treated rats but were decreased significantly after treatment with morin. Administration of morin at 24:00 h caused significantly greater reduction in these parameters than administration at other time points (P<0.05; Duncan's multiple range test). Conclusion: The chronotherapeutic effect of morin in hyperammonemic rats may be due to various factors, including (i) temporal variations of metabolic enzymes involved in the degradation of morin; (ii) temporal variations of lipid peroxidation and of antioxidants, urea cycle enzymes etc.; and (iii) temporal variation in bioavailability of morin. However, the exact underlying mechanism(s) is/are still unclear and further investigations are needed.