Kharroubi Wafa, Dhibi Madiha, Mekni Manel, Haouas Zohra, Chreif Imed, Neffati Fadoua, Hammami Mohamed, Sakly Rachid
Laboratory of Nutrition-Functional Foods and Vascular Diseases, Faculty of Medicine, University of Monaster, Monastir, 5019, Tunisia,
Environ Sci Pollut Res Int. 2014 Oct;21(20):12040-9. doi: 10.1007/s11356-014-3142-y. Epub 2014 Jun 13.
Six groups of rats (n = 10 per group) were exposed to 1 and 10 mg/l of sodium arsenate for 45 and 90 days. Kidneys from treated groups exposed to arsenic showed higher levels of trans isomers of oleic and linoleic acids as trans C181n-9, trans C18:1n-11, and trans C18:2n-6 isomers. However, a significant decrease in eicosenoic (C20:1n-9) and arachidonic (C20:4n-6) acids were observed in treated rats. Moreover, the "Δ5 desaturase index" and the saturated/polyunsaturated fatty acids ratio were increased. There was a significant increase in the level of malondialdehyde at 10 mg/l of treatment and in the amount of conjugated dienes after 90 days (p < 0.05). Significant kidney damage was observed at 10 mg/l by increase of plasma marker enzymes. Histological studies on the ultrastructure changes of kidney supported the toxic effect of arsenate exposure. Arsenate intoxication activates significantly the superoxide dismutase at 10 mg/l for 90 days, whereas the catalase activity was markedly inhibited in all treated groups (p < 0.05). In addition, glutathione peroxidase activity was significantly increased at 45 days and dramatically declined after 90 days at 10 mg/l (p < 0.05). A significant increase in the level of glutathione was marked for the groups treated for 45 and 90 days at 1 mg/l followed by a significant decrease for rats exposed to 10 mg/l for 90 days. An increase in the level of protein carbonyl was observed in all treated groups (p < 0.05). In conclusion, the present study provides evidence for a direct effect of arsenate on fatty acid (FA) metabolism which concerns the synthesis pathway of n-6 polyunsaturated fatty acids and leads to an increase in the trans FAs isomers. Therefore, FA-induced arsenate kidney damage could contribute to trigger kidney cancer.
将六组大鼠（每组n = 10）暴露于1毫克/升和10毫克/升的砷酸钠中，持续45天和90天。暴露于砷的处理组大鼠肾脏中，油酸和亚油酸的反式异构体水平较高，如反式C18:1n-9、反式C18:1n-11和反式C18:2n-6异构体。然而，在处理过的大鼠中观察到二十碳烯酸（C20:1n-9）和花生四烯酸（C20:4n-6）显著减少。此外，“Δ5去饱和酶指数”以及饱和/多不饱和脂肪酸比率增加。在10毫克/升处理时丙二醛水平显著升高，90天后共轭二烯量显著增加（p < 0.05）。通过血浆标志物酶的增加，在10毫克/升时观察到明显的肾脏损伤。对肾脏超微结构变化的组织学研究支持了砷酸盐暴露的毒性作用。砷酸盐中毒在10毫克/升处理90天时显著激活超氧化物歧化酶，而在所有处理组中过氧化氢酶活性均显著受到抑制（p < 0.05）。此外，谷胱甘肽过氧化物酶活性在45天时显著增加，在10毫克/升处理90天后急剧下降（p < 0.05）。在1毫克/升处理45天和90天的组中，谷胱甘肽水平显著升高，随后在10毫克/升处理90天的大鼠中显著下降。在所有处理组中均观察到蛋白质羰基水平升高（p < 0.05）。总之，本研究为砷酸盐对脂肪酸（FA）代谢的直接影响提供了证据，这种影响涉及n-6多不饱和脂肪酸的合成途径，并导致反式脂肪酸异构体增加。因此，脂肪酸诱导的砷酸盐肾脏损伤可能促成引发肾癌。
