González Delgado, M.F., González Zamora, A., Gonsebatt, M.E., Meza Mata, E., García Vargas, G.G., Calleros Rincón, E.Y., and Pérez Morales, R.
Abstract Nitrate pollution has emerged as a problem of great importance because in recent years, the levels of nitrate in soil and groundwater have increased, mainly through anthropogenic activities, such as the use of fertilizers in agriculture, domestic wastewater and septic tanks, industrial waste and deforestation. In animals, nitrate reduction to nitrite (NO 2) and nitric oxide (NO) promote the formation of methemoglobin in the blood and the generation of highly reactive intermediates that induce oxidative stress in target organs. Exposition to nitrates has been associated with methemoglobinemia, reproductive toxicity, metabolic and endocrine alterations and cancer. This study analyzed acute intoxication with sodium nitrate (NaNO 3) in male Wistar rats, aged 12–16 weeks. Four groups with n = 10 rats each were formed: group 1 was the control, and group 2, group 3 and group 4 were treated for 10 days with intragastric doses of 19, 66 and 150 mg/kg/d NaNO 3 , respectively. Hematological, metabolic and histological biomarkers in the liver were analyzed. The results showed high percentages of methemoglobin, an increase in NO 2 in the plasma and an accumulation in the liver. Moreover, there were high counts of white blood cells and platelets in all treated groups. Additionally, there was an increase in the spleen weight in group 4. High levels of glucose, triglycerides, lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were observed and were significantly increased in groups 3 and 4. For oxidative stress biomarkers, there were increases in Thiobarbituric Acid Reactive Substances (TBARS), total GSH and SOD activity, mainly in group 4. Changes in mitochondrial activity were not significant. Histopathological analyses of the liver showed inflammation, infiltration of mononuclear cells, steatosis, ischemia and necrosis, and these findings were more evident at high doses of NaNO 3 in which high of S-nitrosylation were found. In conclusion, NaNO 3 was reduced to NO 2 , thereby inducing methemoglobinemia, whereas other reactive species generated oxidative stress, causing hematological and metabolic alterations and injury to the liver. Graphical abstract fx1 Highlights • Subacute intoxication with NaNO 3 increases the level of NO 2 in the plasma and the percentage of methemoglobin in Wistar rats. • Short term exposition to NaNO 3 causes alterations in white blood cell and platelet counts. • An increase in the dose of NaNO 3 also increases the TBARS and S-nitrosylation levels and triggers the antioxidant response. • Inflammation, steatosis, ischemia and necrosis in the liver were found at a high dose, namely, 150 m/kg/d NaNO 3. [ABSTRACT FROM AUTHOR]