Bouaziz Hanen, Croute Françoise, Boudawara Tahia, Soleilhavoup Jean Pierre, Zeghal Najiba
Laboratoire de Physiologie Animale, Département des Sciences de la Vie, Faculté des Sciences de Sfax, Route de la Soukra-Km 3.5, BP 802, 3018 Sfax, Tunisia.
Exp Toxicol Pathol. 2007 Apr;58(5):339-49. doi: 10.1016/j.etp.2006.11.004. Epub 2007 Jan 30.
To assess renal and liver damages in pregnant and lactating mice as well as in their suckling pups, Wistar female mice were given 500 ppm NaF (226 ppm F-) in drinking water from the 15th day of pregnancy until day 14 after delivery. All mice were sacrificed on day 14 after parturition. In the present work, we evaluated the effects of sodium fluoride on histopathological aspects of kidney, antioxidant status, lipid peroxidation levels and on the expression of four stress proteins (namely, the cytosolic heat shock proteins: HSP72, 73, 90 and the reticulum-associated GRP94). Histological studies have shown many abnormalities in mothers and their pups. Biochemical results showed that lipid peroxidation increased in NaF-treated mice, as evidenced by high kidney and liver thiobarbituric acid reactive substance (TBARS) levels. Alteration of the antioxidant system was confirmed by the significant decline of serum total antioxidant status and of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in red blood cells. Besides, fluoride treatment induced a decrease in serum levels of non-enzymatic antioxidants such as uric acid and of some oligoelements: zinc and copper, known to be cofactors of superoxide dismutase (SOD-Cu-Zn). Compared to control group, the 72kDa protein was found to be overexpressed in kidney of 14-day-old mice only. HSP90 expression in liver appeared moderately inhibited in mothers, but decreased significantly in their pups. No significant changes were detected in the expression of 94kDa protein in both liver and kidney. Results showed that fluoride given to dams led to an oxidative stress in mothers as well as in offspring able to induce enhanced lipid peroxidation levels and protein conformational changes, as suggested by stress protein (HSP, GRP) expression changes.
为了评估怀孕和哺乳期小鼠及其乳鼠的肾和肝损伤情况,将Wistar雌性小鼠从怀孕第15天开始至分娩后第14天,给予含500 ppm NaF(226 ppm F-)的饮用水。所有小鼠在分娩后第14天处死。在本研究中,我们评估了氟化钠对肾脏组织病理学方面、抗氧化状态、脂质过氧化水平以及四种应激蛋白(即胞质热休克蛋白:HSP72、73、90和内质网相关的GRP94)表达的影响。组织学研究显示,母鼠及其幼崽存在许多异常。生化结果表明,经氟化钠处理的小鼠脂质过氧化增加,肾脏和肝脏中硫代巴比妥酸反应性物质(TBARS)水平升高证明了这一点。血清总抗氧化状态以及红细胞中超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性的显著下降证实了抗氧化系统的改变。此外,氟处理导致血清中非酶抗氧化剂如尿酸以及一些微量元素(锌和铜,已知是超氧化物歧化酶(SOD-Cu-Zn)的辅助因子)水平降低。与对照组相比,仅在14日龄小鼠的肾脏中发现72kDa蛋白过度表达。母鼠肝脏中HSP90的表达似乎受到中度抑制,但其幼崽中显著下降。在肝脏和肾脏中均未检测到94kDa蛋白表达的显著变化。结果表明,给母鼠喂食氟会导致母鼠及其后代产生氧化应激,如应激蛋白(HSP、GRP)表达变化所示,这种氧化应激能够诱导脂质过氧化水平升高和蛋白质构象变化。