Aindrila Chattopadhyay

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

Abstract:  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 Krebs 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.

High fat diet aggravates arsenic induced oxidative stress in rat heart and liver

Arsenic is a well known global groundwater contaminant. Exposure of human body to arsenic causes various hazardous effects via oxidative stress. Nutrition is an important susceptible factor which can affect arsenic toxicity by several plausible mechanisms. Development of modern civilization led to alteration in the lifestyle as well as food habits of the people both in urban and rural areas which led to increased use of junk food containing high level of fat. The present study was aimed at investigating the effect of high fat diet on heart and liver tissues of rats when they were co-treated with arsenic. This study was established by elucidating heart weight to body weight ratio as well as analysis of the various functional markers, oxidative stress biomarkers and also the activity of the antioxidant enzymes. Histological analysis confirmed the biochemical investigations. From this study it can be concluded that high fat diet increased arsenic induced oxidative stress.

Mechanism of melatonin protection against copper-ascorbate-induced oxidative damage in vitro through isothermal titration calorimetry

Aims: Involvement of oxidative stress in cardiovascular diseases is well established. Melatonins role as an antioxidant and free radical scavenger via its receptor dependent and receptor independent pathways is well known. The aim of this study is to identify and elaborate upon a third mechanism by which melatonin is able to abrogate oxidative stress. Main methods: Oxidative stress was induced in vitro, by copper (0.2 mM)‐ascorbate (1 mM) in isolated goat heart mitochondria, cytosol and peroxisomes and they were co‐incubated with graded doses of melatonin. Similar experiments in a cell‐free chemical system involving two pure antioxidant enzymes, Cu‐Zn superoxide dismutase and catalase was also carried out. Biochemical changes in activity of these antioxidant enzymes were analysed. Isothermal titration calorimetric studies with pure Cu‐Zn superoxide dismutase and catalase were also carried out. Key findings: Incubation with copper‐ascorbate led to alteration in activity of Cu‐Zn superoxide dismutase and catalase which were found to be protected upon co‐incubation with melatonin (80 &mgr;M for catalase and 1 &mgr;M for others). Results of isothermal titration calorimetric studies with pure Cu‐Zn superoxide dismutase and catalase along with different combinations of copper chloride, ascorbic acid and melatonin suggest that when melatonin is present in the reaction medium along with copper‐ascorbate, it restrains the copper‐ascorbate molecules by binding with them physically along with scavenging the free radicals generated by them. Significance: The present study suggests that possibly, binding of melatonin with antioxidant enzymes masks the vulnerable sites of these antioxidant enzymes, thus preventing oxidative damage by copper‐ascorbate molecules.