Erythrocyte nitric oxide synthase as a surrogate marker for mercury‐induced vascular damage: The modulatory effects of naringin

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), ‐ 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. © 2013 Wiley Periodicals, Inc. Environ Toxicol 29: 1314–1322, 2014.