Ornaghi F, Ferrini S, Prati M, Giavini E
Research and Development Division, Zambon Research S.p.a., Bresso, Milan, Italy.
Fundam Appl Toxicol. 1993 May;20(4):437-45. doi: 10.1006/faat.1993.1054.
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)
N-乙酰-L-半胱氨酸(NAC)因其自由基清除特性以及作为谷胱甘肽(细胞内对抗氧化剂的最重要防御物质之一)的前体,已被广泛用于预防多种化学物质产生的毒性作用。本研究的目的是验证NAC对甲基汞氯化物(MMC)诱导的小鼠胚胎毒性的潜在保护活性。进行了三种实验方法。在第一项研究中,于妊娠第10天给CD雌性小鼠口服MMC(25 mg/kg)进行急性处理,随后立即和/或在24、48和72小时后静脉注射NAC(800 mg/kg)。仅单次给予NAC就完全拮抗了MMC中毒引起的胚胎致死效应,而腭裂发生率相对于NAC给药次数有所降低。在第二项实验中,在妊娠第5至14天的器官形成期对小鼠进行MMC慢性灌胃(3 mg/kg/天口服)。在同一时期,其中一些雌性小鼠还饮用溶解有1% NAC的饮用水。MMC中毒降低了存活胎儿的体重并导致许多腭裂病例。用NAC治疗的MMC中毒母亲所产胎儿的体重有所改善,腭裂发生率在正常范围内。在最后一项实验中,在器官形成期静脉注射NAC(400 mg/kg),显著降低了同期给予MMC(6 mg/kg/天口服)所诱导的严重胚胎致死率。(摘要截断于250字)