Apigenin reverses lung injury and immunotoxicity in paraquat-treated mice

Paraquat (PQ) induces acute lung injury (ALI) and immunotoxicity. Apigenin exerts anti-oxidant and anti-inflammatory properties. The purpose of this study was to investigate the possible protective effects of apigenin on PQ-induced ALI and immunotoxicity in mice. Female C57BL/6 mice received a single injection of PQ (50 mg/kg). Apigenin was given for 7 consecutive days starting 5 days before PQ exposure. The toxicity markers were evaluated in terms of weight loss, lung histopathology, oxidative stress, inflammation, and T cell functions after PQ exposure. Poisoned mice exhibited severe lung tissue lesions, inflammatory cell infiltration and the release of pro-inflammatory cytokines IL-6 and TNF-α. PQ administration increased the lung wet/dry ratios and lipid peroxidation by the increase of MDA levels and decreased anti-oxidase activity including SOD, GSH-PX, and CAT. While such effect on lung was reversed by apigenin. Importantly, PQ-induced immunotoxicity was also observed in a decrease of spleen weight, inhibition of T cell proliferation and T-cell secreting IL-2 from splenocytes. Further mechanism analysis found that PQ administration could decrease total splenocytes, CD4⁺ and CD8⁺ T cells, SOD, GSH-PX, and CAT activity, and increased the levels of MDA and the concentrations of pro-inflammatory cytokines IL-6 and TNF-α compared to control mice. However, apigenin treatment reversed PQ-induced immunotoxicity. In summary, all results suggest that apigenin has beneficial effects on PQ-induced ALI and immunotoxicity possibly, and it could be related, at least in part, to its ability in modulating inflammation and oxidative stress, although in-depth studies might be needed to fully understand the mechanism of action.