The protective effects of N-acetyl-L-cysteine against methyl mercury embryotoxicity in mice.
N-Acetyl-L-cysteine (NAC) has been widely used in the protection against the toxic effects produced by several chemicals because of its radical scavenger properties and because NAC is a precursor of glutathione, one of the most important intracellular defenses against oxidants. The aim of this investigation was to verify the potential protective activity of NAC against the well-known embryotoxicity induced by methyl mercuric chloride (MMC) in mice. Three experimental approaches were carried out. In the first investigation, acute treatment of MMC (25 mg/kg po) was given in CD female mice on Day 10 of pregnancy, and was followed immediately and/or after 24, 48, and 72 hr by administrations of NAC (800 mg/kg i.v.). The embryolethal effects caused by MMC poisoning were completely antagonized by just a single administration of NAC, while the incidence of palatoschisis was reduced in relation to the number of NAC administrations. In the second experiment MMC was chronically gavaged (3 mg/kg/day po) during the period of organogenesis on Days 5 to 14 of gestation. During the same period of time some of these females were also exposed to 1% NAC dissolved in drinking water. MMC poisoning reduced the body weight of viable fetuses and induced many cases of palatoschisis. The body weight of fetuses from MMC-poisoned mothers treated with NAC was improved and the incidence of palatoschisis was in the normal range. In the last experiment the treatment with NAC (400 mg/kg i.v., during the period of organogenesis) drastically reduced the severe embryolethality induced by MMC (6 mg/kg/day po) administered during the same period of time.(ABSTRACT TRUNCATED AT 250 WORDS)
Ornaghi
F
F
Research and Development Division, Zambon Research S.p.a., Bresso, Milan, Italy.
Ferrini
S
S
Prati
M
M
Giavini
E
E
D000014:Abnormalities, Drug-Induced / Q000517:prevention & control; D000111:Acetylcysteine / Q000008:administration & dosage / Q000494:pharmacology*; D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004622:Embryo, Mammalian / Q000187:drug effects*; D005260:Female; D005327:Fetal Resorption / Q000139:chemically induced / Q000517:prevention & control; D007275:Injections, Intravenous; D008767:Methylmercury Compounds / Q000037:antagonists & inhibitors* / Q000633:toxicity; D051379:Mice; D008815:Mice, Inbred Strains; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy
D008767:Methylmercury Compounds; D000111:Acetylcysteine