Harisa Gamaleldin I, Mariee Amr D, Abo-Salem Osama M, Attiaa Sabry M
Department of Pharmaceutics, Kayyali Chair for Pharmaceutical Industry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia; Department of Biochemistry, College of Pharmacy, Al-Azhar University (Boys), Cairo, Egypt.
Environ Toxicol. 2014 Nov;29(11):1314-22. doi: 10.1002/tox.21862. Epub 2013 May 6.
In this study, endothelial nitric oxide synthase activity and nitric oxide (NO) production by human erythrocytes in the presence and absence of mercuric chloride (HgCl2 ), L-arginine (L-ARG), N ω- nitro-L-arginine methyl ester (L-NAME), and naringin (NAR) were investigated. In addition, the levels of reduced glutathione (GSH) and related enzymes were estimated in erythrocytes hemolysate. The protein carbonyl content (PCC) and thiobarbituric acid-reactive substances (TBARS) levels were also determined. The results of this study revealed that the treatment of erythrocytes with either HgCl2 or L-NAME induced a significant decrease in NOS activity and nitrite levels compared with control cells. Furthermore, mercury exposure significantly increased the levels of PCC and TBARS but reduced the GSH level. The activities of glucose-6-phosphate dehydrogenase, glutathione reductase, glutathione peroxidase, and glutathione-S-transferase (GST) were inhibited. The exposure of erythrocytes to HgCl2 in combination with L-ARG, NAR, or both ameliorated the investigated parameters compared with erythrocytes incubated with HgCl2 alone. These results indicate that mercury exposure decreased both erythrocyte NOS activity and nitrite production, and that these parameters might be indicative of mercury exposure. The data also suggest that concomitant treatment with NAR can restore NO bioavailability through either its metal-chelating properties or its antioxidant activity.
在本研究中，我们调查了在有和没有氯化汞（HgCl2）、L-精氨酸（L-ARG）、Nω-硝基-L-精氨酸甲酯（L-NAME）和柚皮苷（NAR）存在的情况下，人红细胞中内皮型一氧化氮合酶活性和一氧化氮（NO）的产生。此外，还估计了红细胞溶血产物中还原型谷胱甘肽（GSH）和相关酶的水平。还测定了蛋白质羰基含量（PCC）和硫代巴比妥酸反应性物质（TBARS）水平。本研究结果显示，与对照细胞相比，用HgCl2或L-NAME处理红细胞会导致NOS活性和亚硝酸盐水平显著降低。此外，汞暴露显著增加了PCC和TBARS水平，但降低了GSH水平。葡萄糖-6-磷酸脱氢酶、谷胱甘肽还原酶、谷胱甘肽过氧化物酶和谷胱甘肽-S-转移酶（GST）的活性受到抑制。与单独用HgCl2孵育的红细胞相比，红细胞同时暴露于HgCl2与L-ARG、NAR或两者会改善所研究的参数。这些结果表明，汞暴露会降低红细胞NOS活性和亚硝酸盐产生，并且这些参数可能指示汞暴露。数据还表明，同时用NAR治疗可以通过其金属螯合特性或抗氧化活性恢复NO生物利用度。
