Mechanism of liver and kidney toxicity in rats induced by subacute inhalation of n-hexane

Background n-Hexane has been widely studied for its neurotoxicity at home and abroad rather than its hepatorenal toxicity. The main metabolizing organ of n-hexane is the liver, and the main excretory organ is the kidney. Whether n-hexane exposure affects hepatic and renal functions and what is the possible mechanism are worth interrogating.

Objective This experiment is designed to observe the hepatorenal toxicity in female rats induced by subacute inhalation of n-hexane and preliminarily explores its possible mechanism.

Methods Forty female SD rats were randomly divided into four groups, namely one control group and three exposure groups which were exposed to n-hexane at 0, 4 212, 12 637, and 37 910 mg·m^-3 respectively by static inhalation, 4 h a day, for continuous 28 d. The rat body weight and liver and kidney organ coefficients after exposure were determined. The pathological changes of liver and kidney were observed. The activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum, as well as the contents of serum creatinine (Scr) and urea nitrogen (BUN) were determined. Real-time fluorescence quantitative PCR was used to detect the mRNA expression levels of CYP1A2 gene in liver and CHOP gene in kidney.

Results Compared with the control group, the body weight of rats in the 37 910mg·m^-3 n-hexane group decreased (P < 0.05), and the changes in the organ coefficients of liver and kidney in each exposure group had no significant difference (P>0.05). With increasing exposure dose, obvious pathological changes were observed in rat liver and kidney tissues under light microscope. Compared with the control group, the serum AST level in the 37 910 mg·m^-3 n-hexane group increased(93.63±6.84) U·L^-1 vs (72.88±11.59) U·L^-1, P < 0.05; the Scr and BUN levels in each exposure group were not significantly different (P>0.05). Compared with the control group (1.00±0.06 for CYP1A2, 1.00±0.04 for CHOP), the expression of CYP1A2 mRNA in liver tissue of each exposure group was down-regulated (0.01±0.00, 0.08±0.07, and 0.14±0.09, respectively; P < 0.05), and the expression of CHOP mRNA was up-regulated (2.22±0.19, 2.05±0.02, and 2.95±0.28, respectively; P < 0.05).

Conclusion Subacute exposure to n-hexane causes liver damage in female rats, possibly triggers endoplasmic reticulum stress in rat kidney tissues, and changes the mRNA expressions of CYP1A2 in liver and CHOP in kidney.