Effects of nitrite graded doses on hepatotoxicity and nephrotoxicity, histopathological alterations, and activation of apoptosis in adult rats

Nitrites are found in several forms; they are widely found in water resources and used as additives and preservatives for food and as a color source. We investigated the hazardous effects of exposing rats to different doses of nitrites. Moreover, we examined such impacts, after acute ingestion, on liver and renal tissues in rats and to what extent this affects the organs' functions. Animals were divided into five groups: one control group 1 (group C) and four sodium nitrite (NaNO2)-treated group (8 rats per group). The four NaNO2-treated groups include group 2 (N20), group 3 (N40), group 4 (N60), and group 5 (N75). NaNO2 was dissolved in distilled water, and single acute dose was orally given by gavage at 20, 40, 60, and 75 mg/kg body weight, respectively. Our results revealed significant increase of liver enzymes activity-aspartate transaminase (AST), alanine aminotransferase (ALT), and creatinine between different groups with increasing doses of nitrite ingestion. The results of hepatic and renal oxidative stress showed significant increase in the malondialdehyde (MDA) levels and significant decrease in the antioxidant parameters, such as reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT), as the dose of nitrite increases. Further, the methemoglobin percent showed significant increase with increasing nitrite doses. Abnormal morphological alterations in the liver and kidney tissues were obviously proportional to the administered nitrite doses. The expression of caspase 3 and Bax level showed enhanced induction of immunoexpression, especially in the high doses of nitrites. On the other hand, the maximal immunoexpression level of anti-apoptotic marker Bcl(2) was found in lower doses of nitrites, whereas marked decrease of Bcl(2) levels was observed in the higher doses. In conclusion, administration of sodium nitrite in a dose-dependent manner is capable of inducing cellular and genetic toxicities and causes disturbance in biochemical analysis, oxidative and anti-oxidative balance, and methemoglobinemia. It also makes histopathological alterations and leads to the activation of apoptosis-related Bax, Bcl(2), and caspase 3 genes of liver and kidney tissues in rats.