Ostensibly ineffectual doses of cadmium and lipopolysaccharide causes liver damage in rats

Various hepatotoxicants co-treated with lipopolysaccharide (LPS) have the potential to cause severe hepatic damage. Whether co-treatment with ostensibly ineffectual (without effect on customary clinical liver function tests, such as aspartate aminotransferase and alanine aminotransferase) doses of cadmium (Cd) and LPS cause liver damage is still unknown. We examined the effects of treating ostensibly ineffectual doses of Cd and LPS on liver dysfunction as well as on liver histopathology. We injected rats with saline only, Cd only, LPS only, or a single ostensibly ineffectual dose of Cd (100 μg/kg body weight) plus LPS (0.1 mg/kg body weight). After 6 h, the rats were killed and their liver damage was assessed. Co-treated with ostensibly ineffectual doses of Cd and LPS had higher levels of aspartate aminotransferase and alanine aminotransferase, hepatic lipid peroxidation, peroxynitrite, nitrite, and interleukin-1β (IL-1β), but lower levels of hepatic metallothionein (MT) than did that treated with saline only, Cd only, and LPS only. Histopathological analysis of Cd only and LPS only showed apparent liver damage, but Cd plus LPS showed marked hepatic damage. We conclude that co-treating the rats with ostensibly ineffectual doses of Cd and LPS is hepatotoxic. Cd promotes LPS-initiated oxidative-stress-associated liver damage by increasing IL-1β and decreasing MT levels in rats.