Department of Food and Nutrition, Hung Kuang University, Taichung 433, Taiwan, ROC.
Environ Toxicol Pharmacol. 2005 Jan;19(1):33-40. doi: 10.1016/j.etap.2004.02.009.
Excessive nitric oxide (NO) production in mice serum and testis due to aluminum (Al) exposure has been shown in previous studies. The aim of this study was to further investigate the role of NO on aluminum-suppressed testosterone level in male CD-1 mice. Each animal in six groups, was given intraperitoneal injections of either saline, aluminum chloride (AlCl(3)), l-N(6)-(1-iminoethyl) lysine (NO synthase inhibitor, l-NIL), or Al chloride along with l-NIL for a period of 12 days. These groups were denoted as C (control, saline), AL (35mg Al/kg/day, saline), NIL240 (total 240mg l-NIL/kg, saline), ALNIL240 (35mg Al/kg/day, total 240mg l-NIL/kg), ALNIL60 (35mg Al/kg/day, total 60mg l-NIL/kg), and NIL60 (total 60mg l-NIL/kg, saline). Results indicated that serum/testicular aluminum levels increased significantly in aluminum-treated animals compared to the controls, whereas the values observed from groups ALNIL240 than AL/ALNIL60 were markedly lower. Aluminum administration significantly increased NO production and decreased both testicular adenosine 3',5'-cyclic monophosphate (cAMP) and testosterone levels. A lower level of NO and higher concentrations of cAMP and testosterone observed in the ALNIL240 group indicated that the protective effect of NO synthase blockage was significant, although incomplete. In addition, aluminum induction significantly elevated the testicular cholesterol, but the values were lower in the ALNIL240 group than the AL or the ALNIL60 group. Finally, it was suggested that aluminum compounds exerted a significant adverse effects on the steroidogenesis and cAMP, which aided in the transport of cholesterol to the inner mitochondrial membrane. Furthermore, nitric oxide synthase blockage prevented aluminum-induced reproductive toxicity.
先前的研究表明，暴露于铝（Al）会导致小鼠血清和睪丸中一氧化氮（NO）的过度产生。本研究旨在进一步探讨 NO 在抑制雄性 CD-1 小鼠睪酮水平中的作用。在 6 组动物中，每组动物均接受腹腔注射生理盐水、氯化铝（AlCl(3)）、L-N(6)-(1-亚氨基乙基）赖氨酸（一氧化氮合酶抑制剂，L-NIL）或 AlCl(3)加 L-NIL，持续 12 天。这些组分别被标记为 C（对照，生理盐水）、AL（35mg Al/kg/天，生理盐水）、NIL240（总 240mg l-NIL/kg，生理盐水）、ALNIL240（35mg Al/kg/天，总 240mg l-NIL/kg）、ALNIL60（35mg Al/kg/天，总 60mg l-NIL/kg）和 NIL60（总 60mg l-NIL/kg，生理盐水）。结果表明，与对照组相比，铝处理动物的血清/睪丸铝水平显著升高，而 ALNIL240 组的观察值明显低于 AL/ALNIL60 组。铝给药显著增加了 NO 的产生，并降低了睪丸中的腺苷 3'，5'-环单磷酸（cAMP）和睪酮水平。在 ALNIL240 组中观察到较低的 NO 水平和较高的 cAMP 和睪酮浓度表明，NO 合酶阻断的保护作用是显著的，尽管并不完全。此外，铝诱导显著增加了睪丸胆固醇，但 ALNIL240 组的值低于 AL 或 ALNIL60 组。最后，研究表明，铝化合物对类固醇生成和 cAMP 产生了显著的不良影响，这有助于胆固醇向线粒体内膜的转运。此外，NO 合酶阻断可防止铝诱导的生殖毒性。
