Effects of N‐acetyl‐L‐cysteine on Teratogenicity of Cadmium in Mice

Abstract

Embryotoxicity and teratogenicity of cadmium (Cd) and modulation of its effects by N-acetyl-L-cysteine (NAC) were evaluated in mice. Pregnant ICR mice were intraperitoneally injected with 3.5 mgikg of CdC12 on day 10 or I 1 of gestation (vaginal plug = day 0). Pregnant mice were pretreated with 160 mgkg of NAC intravenously 2 hours before dosing with CdC12. Pregnant mice were killed on day 17 of gestation. Fetuses were examined for external malformations, especially limb malformations, cleft palate and abnormal palatal rugae. There was little difference in body weight gain of dams during the gestation period in the groups treated with NAC plus Cd as compared with the groups treated with Cd alone. Pretreatment with 160 mgkg of NAC decreased the fetal mortality, incidence of cleft palate and abnormal palatal rugae induced by Cd on day 11.On day 10, pretreatment with NAC decreased the incidence of Cd induced abnormal palatal rugae. These results clearly indicate that NAC exerts protective effects against embryotoxicity and teratogenicity of Cd.Glutathione (GSH), y-glutamylcysteinylglycine, is the most abundant nonprotein thiol in mammalian cells.It is known to be a major intracellular antioxidant, a key component in the metabolism of cysteine and cysteine-containing proteins, and a specific deactivator of potentially toxic electrophilic agents. A number of compounds have been developed to alter the metabolism and intracellular concentration of GSH. N-acetyl-L-cysteine (NAC), a precursor of cysteine, is able to penetrate the cell membrane, and intracellularly it is rapidly deacetylated to L-cysteine by N-acetylases present in different organs (Birnbaum et al., 1952). NAC is also known to increase the intracellular GSH levels in the liver, erythrocytes, and the lung (De Flora et al., 1985). The intracellular GSH levels in different cell systems can be decreased after treatment with diethylmaleate (DEM), D,L-buthionine-S-R-sulfoximine (BSO), and phorone (diisopropylidene acetone) (Meister, 1985).

Effects of Glutathione and Related Compounds on Teratogenicity of 5‐Fluorouracil or Cadmium Hydrochloride in Mice*

“…palatal rugae induced by Cd. There was little difference in limb malformations between the Cd group and Cd plus NAC groups (Naya et al, 1994).…”

“…Pretreatment with NAC decreased the incidence of fetal mortality, cleft palate and abnormal patterns of 5.4f 10.9** **pc0.01 vs. Cd 3.5 mg/kg and saline (Naya et al, 1997). (Naya et al, 1994).…”