A Combination of Melatonin and Alpha Lipoic Acid has Greater Cardioprotective Effect than Either of them Singly Against Cadmium-Induced Oxidative Damage

Mukherjee, Raktim; Banerjee, Sudeep; Joshi, Niraj; Singh, Prem Kumar; Baxi, Darshee; Ramachandran, A. V.

doi:10.1007/s12012-010-9092-9

Cited by 37 publications

(28 citation statements)

References 67 publications

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“…A combination of melatonin and alpha‐lipoic acid has a greater cardio‐protective effect than either of them alone against cadmium‐induced oxidative damage . Melatonin also benefits rat cardiac mitochondria and the survival rate after septic myocardial injury . Furthermore, melatonin protects against isoproterenol‐induced alterations in cardiac mitochondrial energy‐metabolizing enzymes and apoptotic proteins and assists in complete recovery from myocardial injury in rats .…”

Section: Discussionmentioning

confidence: 99%

JAK2/STAT3 activation by melatonin attenuates the mitochondrial oxidative damage induced by myocardial ischemia/reperfusion injury

Yang

Duan

Jin

et al. 2013

Journal of Pineal Research

209

154

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Ischemia/reperfusion injury (IRI) is harmful to the cardiovascular system and causes mitochondrial oxidative stress. Numerous data indicate that the JAK2/STAT3 signaling pathway is specifically involved in preventing myocardial IRI. Melatonin has potent activity against IRI and may regulate JAK2/STAT3 signaling. This study investigated the protective effect of melatonin pretreatment on myocardial IRI and elucidated its potential mechanism. Perfused isolated rat hearts and cultured neonatal rat cardiomyocytes were exposed to melatonin in the absence or presence of the JAK2/STAT3 inhibitor AG490 or JAK2 siRNA and then subjected to IR. Melatonin conferred a cardio-protective effect, as shown by improved postischemic cardiac function, decreased infarct size, reduced apoptotic index, diminished lactate dehydrogenase release, up-regulation of the anti-apoptotic protein Bcl2, and down-regulation of the pro-apoptotic protein Bax. AG490 or JAK2 siRNA blocked melatonin-mediated cardio-protection by inhibiting JAK2/STAT3 signaling. Melatonin exposure also resulted in a well-preserved mitochondrial redox potential, significantly elevated mitochondrial superoxide dismutase (SOD) activity, and decreased formation of mitochondrial hydrogen peroxide (H2 O2 ) and malondialdehyde (MDA), which indicates that the IR-induced mitochondrial oxidative damage was significantly attenuated. However, this melatonin-induced effect on mitochondrial function was reversed by AG490 or JAK2 siRNA treatment. In summary, our results demonstrate that melatonin pretreatment can attenuate IRI by reducing IR-induced mitochondrial oxidative damage via the activation of the JAK2/STAT3 signaling pathway.

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Section: Discussionmentioning

confidence: 99%

JAK2/STAT3 activation by melatonin attenuates the mitochondrial oxidative damage induced by myocardial ischemia/reperfusion injury

Yang

Duan

Jin

et al. 2013

Journal of Pineal Research

209

154

View full text Add to dashboard Cite

show abstract

“…The same study and additional investigations in our laboratory , Genade et al 2008) and elsewhere (Sahna et al 2002b, 2005, Petrosillo et al 2009, Lamont et al 2011 have confirmed that the short-or long-term administration of melatonin at either physiological or pharmacological doses protected the heart against myocardial ischaemia/reperfusion damage. Furthermore, the beneficial effects of exogenous melatonin on the heart in physiological conditions such as ageing as well as in pathophysiological conditions, for example hyperthyroidism (Ghosh et al 2007), cadmium-induced oxidative damage (Mukherjee et al 2011) and myocardial hypertrophy (Reiter et al 2010c) have been demonstrated. However, the mechanism of the actions of melatonin is still complex and not yet fully explored.…”

Section: Cardiovascular Effects Of Melatoninmentioning

confidence: 99%

Melatonin and the metabolic syndrome: a tool for effective therapy in obesity‐associated abnormalities?

2012

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The metabolic syndrome (MetS) is a cluster of metabolic abnormalities associated with increased risk for cardiovascular diseases. Apart from its powerful antioxidant properties, the pineal gland hormone melatonin has recently attracted the interest of various investigators as a multifunctional molecule. Melatonin has been shown to have beneficial effects in cardiovascular disorders including ischaemic heart disease and hypertension. However, its role in cardiovascular risk factors including obesity and other related metabolic abnormalities is not yet established, particularly in humans. New emerging data show that melatonin may play an important role in body weight regulation and energy metabolism. This review will address the role of melatonin in the MetS focusing on its effects in obesity, insulin resistance and leptin resistance. The overall findings suggest that melatonin should be exploited as a therapeutic tool to prevent or reverse the harmful effects of obesity and its related metabolic disorders.

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“…A realistic dose of Cd (5.1 mg/kg) was given to animals by oral gavage for 45 days (Mukherjee et al, 2011). After exposure of animals to Cd, they were made diabetic by i.p.…”

Section: Cadmium Chloride (Cdcl2)mentioning

confidence: 99%

Prior cadmium exposure improves glucoregulation in diabetic rats but exacerbates effects on metabolic dysregulation, oxidative stress, and hepatic and renal toxicity

Singh

Baxi

Diwedi

et al. 2012

Drug and Chemical Toxicology

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The present study was taken up to assess the role of subchronic exposure to an environmentally relevant dosage of cadmium in type l diabetes. Female rats of the Wistar strain were treated with cadmium (5.12 mg/kg body weight) for 45 days. On day 46, rats were made diabetic by alloxan. After 7 days, diabetes (i.e., animals with serum glucose greater than 300 mg/dL) in the alloxanized animals was confirmed and further experiments were conducted for 15 days. Cadmium pretreatment showed disturbed glucose homeostasis with attendant changes in carbohydrate metabolism, coupled with decrease in food and water intake. Disturbance in carbohydrate metabolism was indicated by altered tissue metabolite load, as marked by a decrease in protein and glycogen contents and increased cholesterol store. Poor glucose clearance subsequent to a glucose challenge under the glucose tolerance test was observed in these animals (0.48/min in control vs. 0.13/min in Cd animals). There was a significantly lower glucose elevation rate in the insulin response test subsequent to an insulin-induced decrease in glucose level in Cd-exposed animals. Elevated oxidative stress was marked by increased lipid peroxidation, decreased antioxidant (both nonenzymatic and enzymatic) levels, and serum markers of hepatic and renal damage. Decreased corticosterone levels, together with increased E2 and reduced P4 levels, were some of the hallmark changes in the serum hormone profile of Cd-exposed animals. Overall, the present results are novel and interesting to open more investigations on animal models of type 1 diabetes with a history of previous Cd exposure.

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A Combination of Melatonin and Alpha Lipoic Acid has Greater Cardioprotective Effect than Either of them Singly Against Cadmium-Induced Oxidative Damage

Cited by 37 publications

References 67 publications

JAK2/STAT3 activation by melatonin attenuates the mitochondrial oxidative damage induced by myocardial ischemia/reperfusion injury

JAK2/STAT3 activation by melatonin attenuates the mitochondrial oxidative damage induced by myocardial ischemia/reperfusion injury

Melatonin and the metabolic syndrome: a tool for effective therapy in obesity‐associated abnormalities?

Prior cadmium exposure improves glucoregulation in diabetic rats but exacerbates effects on metabolic dysregulation, oxidative stress, and hepatic and renal toxicity

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