Protective role of melatonin in myocardial oxidative damage induced by mercury in murine model.
This study was designed to investigate the electrophysiological, hemodynamic and biochemical parameters of mercuric chloride and methylmercury exposure on cardiovascular functions and its modulation by melatonin in vivo. Wistar albino rats were divided into six group containing 10 animals each. Mercuric chloride (3.75 µM/L) in drinking water and methylmercury (0.5 mg/kg/day) through gavage, given for 1 month, induced a statistically significant increase (p < 0.001) in left ventricular end diastolic pressure, blood and cardiac tissue mercury content and myocardial lipid peroxides compared to control. Significant attenuation (p < 0.05) of baroreflex sensitivity and depletion of myocardial endogenous antioxidants (p < 0.001) viz. Reduced glutathione (GSH) and superoxide dismutase (SOD) were also found in the mercury-exposed groups as compared to control group. Mercury exposure followed by subacute treatment with melatonin (4 µg/mL/day) in drinking water for 1 month significantly lowered (p < 0.01) left ventricular end diastolic pressure and lipid peroxide levels and increased baroreceptor sensitivity (p < 0.001) and also levels of GSH and SOD (p < 0.001) as compared to mercury-exposed rats. The results of our study provide clear evidence that elevated oxidative stress and altered baroreflex mechanisms caused by mercury intoxication may be the contributing factors responsible for impairment of cardiovascular functions and melatonin may exhibit cardioprotective property against subacute heavy metal intoxication and enhance the antioxidant defense against mercury-induced oxidative myocardial injury in rats.
Department of Pharmacology, University College of Medical Sciences & GTB Hospital, Delhi, India.
Mitali
M
Jindal
Gobind Rai
GR
Garg
Pramod Kumari
PK
Mediratta
Mohammad
M
Fahim
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D005260:Female; D005978:Glutathione / Q000097:blood; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008550:Melatonin / Q000494:pharmacology*; D008627:Mercuric Chloride / Q000097:blood / Q000633:toxicity*; D008767:Methylmercury Compounds / Q000097:blood / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000097:blood
D000975:Antioxidants; D008767:Methylmercury Compounds; D020011:Protective Agents; D008315:Malondialdehyde; D008627:Mercuric Chloride; D013482:Superoxide Dismutase; D005978:Glutathione; D008550:Melatonin