Hepatoprotective effect of pyridoxal phosphate against lead poisoning by inhibiting Kupffer cell hyperplasia due to a decrease in oxidative stress associated with hepatic NF-kβ.

Lead (Pb) induces tissue damage by elevating oxidative stress and activating the nuclear factor-κB (NF-κB) signaling pathway. This study aimed to investigate the effects of pyridoxal phosphate (PLP) on hepatic NF-kβ expression and endogenous antioxidant capacity. Additionally, we evaluated biochemical parameters and histological features of the liver. Forty-four rats were divided into four equal groups: a normal, an untreated lead toxicity rat model (Pbt), and two treated groups receiving PLP at of 90 mg/L and 180 mg/L in their drinking water for one month. Pb intoxication was induced by administrating of 50 mg/L of lead acetate in the drinking water over the same period. Oxidative stress and inflammatory markers were measured in serum and liver homogenates. Additionally, liver biochemical parameters, histological features, and NF-kB expression were also analyzed. PLP demonstrated a dose-dependent protective effect against Pb intoxication. Both lower and higher doses of PLP mitigated liver injury by inhibiting Kupffer cell hyperplasia, which linked to a reduction in the NF-kβ/BACT ratio and an enhancement of antioxidant capacity. The higher dose of PLP also prevented Pb-induced histopathological changes in the liver and exhibited a more pronounced positive effect on liver function. PLP exhibited a dose-dependent protective effect on the liver against Pb poisoning by inhibiting the overgrowth of Kupffer cells and reducing myeloperoxidase (MPO) activity through the regulation of hepatic NF-kB with GSH. Consequently, enhancing the GSH/GSSG ratio and stimulating antioxidant enzymes offers a promising strategy for mitigating Pb toxicity.