Lulu Xu
China Pharmaceutical University, China
Title: Demethyleneberberine attenuates isoniazid-induced-liver injury by reducing CYP2E1 expression and preventing endoplasmic reticulum stress
Biography
Biography: Lulu Xu
Abstract
With the wide clinically application of isoniazid (INH) for tuberculosis treatment, its hepatotoxicity is emerging as a most common adverse effect. Demethyleneberberine (DMB) is a natural product existing in Chinese herb, which plays an important role in protecting against liver disease.
Methods: To investigate the potential effect of DMB against INH-induced liver injury, 8-week-old male C57 mice were given INH (150mg/kg) for 3 weeks. The mice were administrated DMB (10 and 20mg/kg) or a positive control drug Tiopronin (50mg/kg) via enterocoelia concurrently. Serum levels of aspartate aminotransferase (AST), and liver homogenate glutathione (GSH), malondialdehyde (MDA), total cholesterol (TC) and triglyceride (TG) were measured. The expression levels of CYP2E1 and ER stress associative protein were determined. Section of livers were collected for photographic and microscopic observation by hematoxylin and eosin (HE) staining.
Results: DMB protected the liver function with significantly lowered the serum AST lever. Lipid-lowering effect of DMB was observed with reductions in liver TG and TC, which consisted with the observation of HE stained sections, reflected that DMB dose-dependently reversed the INH-induced-liver injury, as there were much less lipid droplets depositing inside the parenchyma cells. The benefits of DMB were associated with increased GSH and decreased MDA activity and CYP2E1 expression in the livers. Further more DMB remarkably inhibited ER stress by downregulating UPR (GRP78) and ATF4-CHOP pathway.
Conclusion: DMB exerts protective effect against INH-induced-liver injury in mice, which maybe associated with its regulation of lipid metabolism, reduction of CYP2E1 expression and inhibition of ER stress.