Selvaraju Subash

Morin a flavonoid exerts antioxidant potential in chronic hyperammonemic rats: a biochemical and histopathological study

Plant flavonoids are emerging as potent therapeutic drugs effective against a wide range of free radical-mediated diseases. Morin (3,5,7,2′,4′-pentahydroxyflavone), a member of flavonols, is an important bioactive compound by interacting with nucleic acids, enzymes and protein. In this study, we found that morin (30xa0mg/kg body weight) by oral administration offers protection against hyperammonemia by means of reducing blood ammonia, oxidative stress and enhancing antioxidant status in ammonium chloride-induced (100xa0mg/kg body weight; i.p) hyperammonemic rats. Enhanced blood ammonia, plasma urea, lipid peroxidation in circulation and tissues (liver and brain) of ammonium chloride-treated rats was accompanied by a significant decrease in the tissues levels of superoxide dismutase (SOD), catalase, reduced glutathione (GSH) and glutathione peroxidase (GPx). Morin administered rats showed a significant reduction in ammonia, urea, lipid peroxidation with a simultaneous elevation in antioxidant levels. Cotreatment with morin prevented the elevation of liver marker enzymes induced by ammonium chloride. The body weight of the animals decreased significantly on ammonium chloride administration when compared with control group. However, cotreatment with morin significantly prevented the decrease of the body weight caused by ammonium chloride. Hyperammonemic rats show liver fibrosis, steatosis, sinusoidal dilatation, etc., along with necrosis, microcystic degeneration in brain. All these changes were reduced in hyperammonemic rats treated with Morin, which too correlated with the biochemical observations. In conclusion, these findings indicate that morin exert antioxidant potential and offer protection against ammonium chloride-induced hyperammonemia. But the exact underlying mechanism needs to be elucidated.

Constant light influences the circadian oscillations of circulatory lipid peroxidation, antioxidants and some biochemical variables in rats

Abstract Temporal oscillations of circulatory thiobarbituric acid reactive substances (TBARS), antioxidants such as reduced glutathione (GSH), superoxide dismutase (SOD), and catalase and glucose, cholesterol, total protein and aspartate transaminase (AST) were studied under LD (12:12 h) and constant light (LL) (500 lux) conditions after exposing the animal for 21 days. Advances in the acrophase of GSH, SOD, catalase, glucose, total protein and (AST) rhythms and delays in TBARS and cholesterol were found; amplitude and mesor values of these rhythms were found to be altered during constant light treatment. The above said circadian alterations during LL exposure may be due to (1) formation of photooxidants and stress mediated lipid peroxidation, suppression of melatonin (2) modulation of neuroendocrine and neurotransmitters rhythm (3) suppression of sleep – wake cycle (4) feeding and locomotion rhythm. The exact mechanism still remains to be explored and further research needed.

Chronotherapeutic effect of morin in experimental chronic hyperammonemic rats

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 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.

Impact of morin (a bioflavonoid) on ammonium chloride-mediated oxidative damage in rat kidney

Introduction : Hyperammonemia is a major contributing factor to neurological abnormalities observed in hepatic encephalopathy and in congenital defects of ammonia detoxification. Ammonia toxicity results in free radical generation that leads to oxidative stress and tissue damage. Morin is a bioflavonoid, a constituent of many herbs and fruits that are used as herbal medicines and also several biological activities. Our aim is to investigate the effect of morin on blood ammonia and plasma urea as well as kidney lipid peroxidation, and the antioxidant status in ammonium chloride-induced hyperammonemic rats. Materials and Methods: Male albino Wistar rats weighing 180 - 200 g were used for the study. Hyperammonemia was induced by interaperitonial injection of ammonium chloride (100 mg / kg body weight). The rats were treated with morin (30 mg / kg body weight) via oral administration. Administration of morin in hyperammonemic rats reduced the levels of ammonia and urea. The antioxidant property of morin was studied by assessing the activities of thiobarbituric acid reactive substances (TBARS), hydroperoxides (HP), conjugated dienes (CD), and antioxidants superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH) in ammonium chloride-treated rats. Results and Conclusions: Kidney oxidative stress was effectively modulated by morin administration. Morin significantly improved the status of kidney antioxidants and decreased the levels of ammonia, urea, TBARS, HP, and CD, as compared to the ammonium chloride-treated group. The study offers evidence for the antihyperammonemic and antioxidant effects of morin against oxidative stress in the kidney, induced by ammonium chloride.

Aspartate modulates the circadian patterns of a few biochemical variables in Wistar rats

Abstract D-aspartate was used to demonstrate possible sources of excitatory input to the suprachiasmatic nucleus (SCN) in rats. Aspartate (50 mg/kg bodyweight) was orally administrated chronically for 60 days to Wistar rats and 24 h rhythmic patterns of glucose, cholesterol, total protein and aspartate transaminase (AST) were studied under light – dark (LD 12:12 h) cycle. Our results showed acrophase advances in glucose and delays in cholesterol and AST rhythms. Increased mesor and altered amplitude values were found in all rhythms; aspartate levels in the brain were found to be significantly increased in aspartate treated animals. We hypothesised that the altered biochemical rhythms in aspartate treated rats could be due to (1) modulation of neurotransmission in SCN, (2) behavioural rhythms and (3) feeding rhythms.

Protective effect of morin on lipid peroxidation and lipid profile in ammonium chloride–induced hyperammonemic rats

Abstract Objective To evaluated the protective effects of morin (3, 5, 7, 2′, 4′-pentahydroxyflavone) on lipid peroxidation and lipid levels during ammonium chloride (AC) induced hyperammonemia in experimental rats. Methods Thirty two male albino Wistar rats, which are weighing between 180–200 g were used for the study. The hyperammonemia was induced by administration of 100 mg/kg body weight ( i.p. ) thrice in a week of AC for 8 weeks. Rats were treated with morin at dose (30 mg/kg body weight) via intragastric intubations together with AC. At the end of experimental duration, blood ammonia, plasma urea, lipid peroxidation indices [thiobarbituric acid reactive substances, hydroperoxides and lipid levels (cholesterol, triglycerides, free fatty acids and phospholipids)] in serum and tissues were analysed to evaluate the antiperoxidative and antilipidemic effects of morin. Results Ammonia, urea, lipid peroxidative indices and lipid levels were significantly increased in AC administered group. Morin treatment resulted in positive modulation of ammonia, urea, lipid peroxidative indices and lipid levels. Morin administration to normal rats did not exhibit any significant changes in any of the parameters studied. Conclusions It can be concluded that the beneficial effect of morin on ammonia, urea, lipid peroxidative indices and lipid levels could be due to its antioxidant property.

Effect of N-phthaloyl gamma-aminobutyric acid on lipid peroxidation, antioxidants and liver markers in constant light exposed rats

Introduction & Materials and Methods : The effect of N-Phthaloyl GABA on the levels of circulatory lipid peroxidation products such as TBARS (thiobarbituric acid reactive substances), antioxidants: SOD (superoxide dimutase), CAT (catalase), GSH (reduced glutathione), and GPx (glutathione peroxidase), liver markers such as AST (aspartate transaminase), ALT (alanine transaminase), and ALP (alkaline phosphatase), were studied for its protective effect during constant light (LL) exposure in rats. Results: A significant increase in the levels of circulatory TBARS, AST, ALT, and ALP were found in LL exposed rats. These changes were significantly decreased in N-Phthaloyl GABA and LL-exposed rats. The levels of antioxidants were significantly decreased in LL-exposed rats and administration of GABA normalized these changes. Conclusions: Our results indicated that NPhthaloyl GABA offered protection by influencing the levels of the lipid peroxidation products, antioxidants, and liver markers during LL-exposed stress. This might be due to the antistress, anticonvulsant, antinociceptive, and antiulcer activities of N-Phthaloyl GABA. The exact mechanism remains to be explored and further research is needed.

Influence of N-phthaloyl gamma-aminobutyric acid on circadian rhythms of lipid peroxidation products and antioxidants

Abstract N-Phthaloyl GABA was administrated daily (50 mg/kg body weight-i.p) to Wistar rats for 21 days and circadian rhythms of thiobarbituric acid reactive substances (TBARS) and antioxidants such as reduced glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD) were studied. N-Phthaloyl GABA was found to delay TBARS and to advance GSH, CAT and SOD acrophases. Amplitude and mesor values of these rhythms were found to be altered during N-Phthaloyl GABA treatment. Since GABA is hypothesized to be involved in conveying dark information to clock, exogenous administration of P-GABA might alter the photic information received by the clock. Our study shows that P-GABA administration alters the temporal patterns of lipid peroxidation and antioxidants in Wistar rats. But the exact mechanism remains to be explored and further research is needed.