In vivo protection of a water-soluble derivative of vitamin E, Trolox, against methylmercury-intoxication in the rat.
Methylmercury (MeHg) is a well-known neurotoxicant. MeHg-intoxication causes a disturbance in mitochondrial energy metabolism in skeletal muscle and apoptosis in cerebellum. We report the first in vivo effectiveness of antioxidant Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carhoxylic acid), a water soluble vitamin E analog, against the MeHg-induced cellular responses. Treatment with Trolox (6-hydroxy-2.5,7,8-tetramethylchroman-2-carboxylic acid) clearly protects MeHg-treated rat skeletal muscle against the decrease in mitochondrial electron transport system enzyme activities despite the retention of MeHg. Tdt-mediated dUTP nick-end-labeling method clarified that Trolox is effective for protecting cerebellum from MeHg-induced apoptosis. These data indicate that MeHg-mediated oxidative stress plays an important role in the in vivo pathological process of MeHg intoxication. Trolox may prevent some of clinical manifestations of MeHg-intoxication in humans.
Usuki
F
F
Department of Clinical Medicine, National Institute for Minamata Disease, 4058-18 Hama, Minamata 867-0008, Japan. usuki@nimd.go.jp
Yasutake
A
A
Umehara
F
F
Tokunaga
H
H
Matsumoto
M
M
Eto
K
K
Ishiura
S
S
Higuchi
I
I
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002839:Chromans / Q000494:pharmacology*; D004579:Electron Transport / Q000187:drug effects; D008297:Male; D008628:Mercury / Q000378:metabolism; D008767:Methylmercury Compounds / Q000037:antagonists & inhibitors* / Q000506:poisoning*; D008931:Mitochondria, Muscle / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010088:Oxidoreductases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D014867:Water
D000975:Antioxidants; D002839:Chromans; D008767:Methylmercury Compounds; D014867:Water; D010088:Oxidoreductases; D008628:Mercury; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid