Hormetic association between sodium nitrate and liver enzymes: a study in female and male rats

This study aims to evaluate the long-term dose-dependent effects of sodium nitrate on serum ALT, AST, and ALP in healthy female and male rats. A total of 120 rats (60 females and 60 males) were divided into 6 subgroups (n = 10). In each sex, a control group received regular tap water, while five treatment groups received sodium nitrate in tap water (50, 100, 150, 250, and 500 mg/L). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and nitric oxide (NO) metabolites (NOx) were measured at baseline (month 0) and after 6 mo. Hormetic zones for sodium nitrate in female rats were 10-230 mg/L for ALT, 20-180 mg/L for AST, and 8-270 mg/L for ALP. In males, the zones were 5-190 mg/L for ALT, 7-180 mg/L for AST, and 7-265 mg/L for ALP. Serum NOx levels were negatively correlated with ALT (r = -0.498) and AST (r = -0.320) at moderate doses (100-150 mg/dL) but positively correlated with ALT (r = 0.500) and AST (r = 0.300) at higher doses (250-500 mg/dL (all P < 0.05). Sodium nitrate exhibited a J-shaped dose-response relationship with liver function tests (LFTs) in both female and male rats. Protective effects were observed at moderate doses (100 mg/L for ALT and AST; 150 mg/L for ALP), while low doses (<10 mg/L) were ineffective, and high doses (>200 mg/L for ALT/AST; >250 mg/L for ALP) were toxic. These findings highlight the dual potential of sodium nitrate as both beneficial and harmful, depending on the dosage in healthy state.