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© 1993 Oxford University Press

research-article

The Protective Effects of N-Acetyl-L-cysteine against Methyl Mercury Embryotoxicity in Mice

F. ORNAGHI*, S. FERRINI*, M. PRATI{dagger} and E. GIAVINI{dagger}

*Research and Development Division, Zambon Research S p a Bresso, Milan, Italy {dagger}Department of Biology, University of Milan Milan, Italy

Received February 4, 1992; accepted December 29, 1992

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 iv). 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/day iv, 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. In all experiments the administration of NAC antagonized the skeletal ossification delay induced by MMC poisoning. Our experimental results demonstrate a definitive protective activity of NAC against MMC-induced teratogenicity and embryopathy in mice.


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