Protective effect of caffeic acid phenethyl ester against imidacloprid-induced hepatotoxicity by attenuating oxidative stress, endoplasmic reticulum stress, inflammation and apoptosis.
Pestic Biochem Physiol. 2020 Mar ;164:122-129. Epub 2020 Jan 7. PMID: 32284117
Imidacloprid (IMI) is a widely used neonicotinoid pesticide in the world, its environmental and human health risk has particularly attracted the attention of researchers. Caffeic acid phenethyl ester (CAPE), an active polyphenol of propolis, has many pharmacological activities including free radical scavenger, anti-inflammatory, and anti-oxidant. In this study, protective effect of CAPE against IMI induced liver injury in mice was performed. Administration of 1 and 2.5 mg/kg CAPE markedly prevented serum AST and ALT increase in 5 mg/kg IMI-induced mice. CAPE significantly downregulated liver NO generation and lipid peroxidation, and upregulated glutathione, catalase, superoxide dismutase and glutathione peroxidase in a dose-dependent manner in liver of IMI-induced mice. Endoplasmic reticulum stress represented by the swelling of endoplasmic reticulum was observed by transmission electron microscope in IMI group. Pretreatment of 2.5 mg/kg CAPE significantly attenuated the endoplasmic reticulum stress induced by IMI in liver. Western blot analysis illustrated that pretreatment of CAPE downregulated the upregulation of TNF-α and IFN-γ induced by IMI in liver of mice. Moreover, the increase of positive apoptotic hepatocytes further suggested apoptosis might be involved in IMI-induced hepatotoxicity. Pretreatment of 1 and 2.5 mg/kg CAPE significantlydecreased positive apoptotic hepatocytes, suggested that CAPE prevented apoptosis in liver of IMI-induced mice. In conclusion, CAPE prevented liver injury in IMI-induced mice via attenuation of oxidative stress, endoplasmic reticulum stress, inflammation and apoptosis. Our findings may have broad biological and environmental implications for future research on the therapeutic strategy to prevent liver injury induced by pesticides.