Protective effects of Ca2+ channel blockers against methyl mercury toxicity.
The protective effects of Ca2+ channel blockers against the toxicity of methyl mercury were examined by both in vivo and in vitro experiments. In the in vivo study we first examined the effects of the Ca2+ channel blockers (20 mg/kg/day), flunarizine, nifedipine, nicardipine, and verapamil against the toxic level of methyl mercury treatment (5 mg/kg/day of methyl mercuric chloride for 12 consecutive days). However, there was a difference in potency of the effects among the reagents. All the Ca2+ channel blockers prevented a decrease in body weight and/or the appearance of the symptoms of neurological disorders in the rats treated with methyl mercury. In the next experiment, we examined flunarizine at different levels of supplementation (1, 25 and 50 mg/kg/day). Flunarizine in a dose-dependent manner prevented a decrease in body weight, appearance of the symptoms of neurological disorder and mortality in the rats treated with methyl mercury. Flunarizine treatment (25 mg/kg/day) for the first 5 days did not affect mercury distribution among the tissues, suggesting that the mechanism of protection against methyl mercury-induced toxicity may be attributed to its own pharmacological effect. In the in vitro study we examined the effect of flunarizine (0, 0.5, 5 and 50 microM) using primary cultures of cerebellar granular cells in 96-well culture plates. Viable cell numbers were estimated 1 and 3 days after treatment with methyl mercury. The estimated 50% lethal concentration (LC50) of methyl mercury was higher in plates treated with 5 and 50 microM of flunarizine both on days 1 and 3, indicating that flunarizine protected the primary cultured cerebellar granular cells against the toxicity of methyl mercury. As such, Ca2+ channel blockers protected against the toxicity of methyl mercury both in vivo and in vitro, suggesting that Ca2+ plays an important role in the mechanisms of methyl mercury toxicity.
Sakamoto
M
M
Department of Epidemiology, National Institute for Minamata Disease, Minamata City, Japan.
Ikegami
N
N
Nakano
A
A
D000818:Animals; D001769:Blood / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D002493:Central Nervous System Diseases / Q000517:prevention & control; D007674:Kidney Diseases / Q000517:prevention & control; D008107:Liver Diseases / Q000517:prevention & control; D008297:Male; D008767:Methylmercury Compounds / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
D002121:Calcium Channel Blockers; D008767:Methylmercury Compounds