Rat liver mitochondrial damage under acute or chronic carbon tetrachloride-induced intoxication: Protection by melatonin and cranberry flavonoids

Abstract

In current societies, the risk of toxic liver damage has markedly increased. The aim of the present work was to carry out further research into the mechanism(s) of liver mitochondrial damage induced by acute (0.8 g/kg body weight, single injection) or chronic (1.6 g/ kg body weight, 30 days, biweekly injections) carbon tetrachlorideinduced intoxication and to evaluate the hepatoprotective potential of the antioxidant, melatonin, as well as succinate and cranberry flavonoids in rats. Acute intoxication resulted in considerable impairment of mitochondrial respiratory parameters in the liver. The activity of mitochondrial succinate dehydrogenase (complex II) decreased (by 25%, p b 0.05). Short-term melatonin treatment (10 mg/kg, three times) of rats did not reduce the degree of toxic mitochondrial dysfunction but decreased the enhanced NO production. After 30-day chronic intoxication, no significant change in the respiratory activity of liver mitochondria was observed, despite marked changes in the redox-balance of mitochondria. The activities of the mitochondrial enzymes, succinate dehydrogenase and glutathione peroxidase, as well as that of cytoplasmic catalase in liver cells were inhibited significantly. Mitochondria isolated from the livers of the rats chronically treated with CCl 4 displayed obvious irreversible impairments. Long-term melatonin administration (10 mg/kg, 30 days, daily) to chronically intoxicated rats diminished the toxic effects of CCl 4 , reducing elevated plasma activities of alanine aminotransferase and aspartate aminotransferase and bilirubin concentration, prevented accumulation of membrane lipid peroxidation products in rat liver and resulted in apparent preservation of the mitochondrial ultrastructure. The treatment of the animals by the complex of melatonin (10 mg/kg) plus succinate (50 mg/kg) plus cranberry flavonoids (7 mg/kg) was even more effective in prevention of toxic liver injury and liver mitochondria damage.

Melatonin Prevents Chemical-Induced Haemopoietic Cell Death

“…In fact, there is evidence that mitochondria may have the capacity to synthesize and metabolize MEL [49,50]. It has been demonstrated that MEL pharmacological doses affected the mitochondrial function and prevented mitochondrial dysfunction under pathological conditions [51–53]. In addition, a recent paper [54] reported that MEL ability in reducing cell damage seems due to its capacity in decreasing oxidative stress and in stimulating GHS level.…”

Myricitrin exhibits antioxidant, anti-inflammatory and antifibrotic activity in carbon tetrachloride-intoxicated mice

“…Therefore, the investigation of hepatoprotective activity of foods, medicinal plants and their bioactive constituents is one of the major goals in medical research today. Carbon tetrachloride (CCl 4 )-intoxication is a common animal model for studying the mechanism of liver injury as well as hepatoprotective activity of natural and synthetic compounds [3]. There is increasing evidence to suggest that the antioxidant properties of food phenolics is beneficial to liver health, including protection against chemically-induced hepatotoxicity [4][5][6][7].…”

Anti-inflammatory and hepatoprotective effects of Ganoderma lucidum polysaccharides on carbon tetrachloride-induced hepatocyte damage in common carp (Cyprinus carpio L.)

“…The pathogenesis of CCl 4 induced hepatic injury is multifactorial, ranging from inflammation and oxidative stress to immunological and apoptotic reactions. CCl 4 has been shown leading to the loss of antioxidant components such as SOD and CAT [5]. Although, there is great advance in understanding the molecular pathology of liver injury, there have been no effective treatments for the fish hepatobiliary syndrome [6]; hence the search for plant-based remedies is of considerable interest to researchers and aquatic medicine producers.…”