Mechanisms of isoproterenol-induced cardiac mitochondrial damage: protective actions of melatonin.

Mitochondrial dysfunction due to oxidative damage is the key feature of several diseases. We have earlier reported mitochondrial damage resulting from the generation of oxidative stress as a major pathophysiological effect of isoproterenol (ISO)-induced myocardial ischemia in rats. That melatonin is an antioxidant that ameliorates oxidative stress in experimental animals as well as in humans is well established. We previously demonstrated that melatonin provides cardioprotection against ISO-induced myocardial injury as a result of its antioxidant properties. The mechanism of ISO-induced cardiac mitochondrial damage and protection by melatonin, however, remains to be elucidated in vitro. In this study, we provide evidence that ISO causes dysfunction of isolated goat heart mitochondria. Incubation of cardiac mitochondria with increasing concentrations of ISO decreased mitochondrial succinate dehydrogenase (SDH) activity, which plays a pivotal role in mitochondrial bioenergetics, as well as altered the activities of other key enzymes of the Kreb's cycle and the respiratory chain. Co-incubation of ISO-challenged mitochondria with melatonin prevented the alterations in enzyme activity. That these changes in mitochondrial energy metabolism were due to the perpetration of oxidative stress by ISO was evident from the increased levels of lipid peroxidation and decreased reduced glutathione/oxidized glutathione ratio. ISO-induced oxidative stress also altered mitochondrial redox potential and brought about changes in the activity of the antioxidant enzymes manganese superoxide dismutase and glutathione peroxidase, eventually leading to alterations in total ATPase activity and membrane potential. Melatonin ameliorated these changes likely through its antioxidant abilities suggesting a possible mechanism of cardioprotection by this indole against ISO-induced myocardial injury.

Protective effect of aqueous garlic extract against lead-induced hepatic injury in rats.

Effect of aqueous extract of garlic on hepatic injury due to lead-induced oxidative stress in experimental rats has been investigated. Lead acetate (LA) at a dose of 15 mg/kg body wt was administered ip to rats for 7 consecutive days to induce hepatic injury. Freshly prepared aqueous garlic extract (AGE) at a dose of 50 mg/kg body wt was fed orally to rats 1 h before LA treatment for similar period. LA treatment caused hepatic injury as evident from increased activities of serum glutamate pyruvate transaminase (SGPT) and alkaline phosphatase (ALP), increased serum bilirubin level and damage in the tissue morphology. Lead-induced oxidative stress in liver was evident from increased levels of lipid peroxidation and reduced glutathione. The decreased activity of superoxide dismutase (SOD) and an increased activity of catalase as well as an increased activity of xanthine oxidase (XO) indicate generation and possible accumulation of reactive oxygen intermediates. Furthermore, altered activities of lactate dehydrogenase (LDH), isocitrate dehydrogenase (ICDH), alpha-keto glutarate dehydrogenase (alpha-KGDH) and succinate dehydrogenase (SDH) also indicate an impaired substrate utilization and generation of oxidative stress. All these changes were found to be mitigated when the rats were pre-treated with the AGE. Results indicate that AGE has the potential to ameliorate lead-induced hepatic injury due to oxidative stress in rats. The protective effects may be due to the antioxidant properties of AGE and may have future therapeutic relevance.

Melatonin protects against isoproterenol-induced myocardial injury in the rat: antioxidative mechanisms.

The present study was undertaken to explore the protective effect of melatonin against isoproterenol bitartrate (ISO)-induced myocardial injury in rat. Treatment of rats with ISO increased the level of lipid peroxidation products and decreased the reduced glutathione levels in cardiac tissue indicating that this synthetic catecholamine induces oxidative damage following oxidative stress. Pretreatment of ISO-injected rats with melatonin at a dose of 10 mg/kg body weight, i.p. prevented these changes. Additionally, melatonin also restored the activities and the levels of antioxidant enzymes which were found to be altered by ISO treatment. Treatment of rats with ISO resulted into an increased generation of hydroxyl radicals with melatonin pretreatment significantly reducing their production. Finally, treatment of rats with ISO caused a lowering of systolic pressure with reduced cardiac output and diastolic dysfunction whereas melatonin pretreatment significantly restored many of these parameters to normal. The findings document melatonin's ability to provide cardio protection at a low pharmacological dose. Melatonin has virtually no toxicity which raises the possibility of this indole being a therapeutic treatment for ischemic heart disease.

Protective effect of aqueous Curry leaf (Murraya koenigii) extract against cadmium-induced oxidative stress in rat heart.

Treatment of rats with a low dose of cadmium chloride caused a significant damage in the rat cardiac tissue indicated by the increase in the level of serum glutamate oxaloacetate transaminase and lactate dehydrogenase1 activities. Histological studies confirmed the damage due to cadmium. That cadmium-induced tissue damage was caused due to oxidative stress was evident from the changes observed in the levels of lipid peroxidation and reduced glutathione, the protein carbonyl content, and the alterations in the activities of cardiac antioxidant and pro-oxidant enzymes. Treatment of rats with cadmium also caused alterations in the activities of mitochondrial Kreb's cycle as well as respiratory chain enzymes. All these changes were ameliorated when the rats were pre-treated with an aqueous extract of Curry leaf (Murraya koenigii). The studies indicated that the aqueous extract of Curry leaf protects the rat cardiac tissue against cadmium-induced oxidative stress possibly through its antioxidant activity. As curry leaf is consumed by people as part of their diet in India and South-East Asian and some European countries as well, and, as it has no reported side-effects, the results seem to have relevance at places where humans are exposed to cadmium environmentally or occupationally.