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Regulation of il-1 and TNF-α on metabolic enzyme cyp2e1 in immunological liver injury in rats / 中国药理学通报
Chinese Pharmacological Bulletin ; (12): 1160-1164, 2019.
Article in Chinese | WPRIM | ID: wpr-857187
ABSTRACT
Aim To investigate the regulation and mechanism of inflammatory cytokines interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) on the drug metabolism enzyme cytochrome P450 2E1 (CYP2E1) during immune-mediated liver injuryMethods By injection of Bacillus Calmette-Guerin(BCG, 125 mg·kg-1) prepared rat model of immunological liver damage. To detection of CYP2E1 probe drug chlorzoxazone in blood concentration changes of rats over time reflects its metabolic activity by high-performance liquid chromatography (HPLC) assay. The changes of IL-1β and TNF-α in liver tissue of rats were detected by ELISA. The expression of CYP2E1 protein was determined by Western blot analysis. Results After 14 days of BCG injection of rats, a large number of mononuclear cells and lymphocytes infiltrated around the liver parenchyma and the portal area, resulting in a large number of granuloma masses with different sizes and diffuse distribution, IL-1β and TNF-α high expression (P < 0.01), CYP2E1 metabolic activity and protein expression were significantly decreased (P < 0.05). The protein content of CYP2E1 was significantly negatively correlated with IL-1β (r=0.222, P=0.027). Activation of PDTC-mediated nuclear factor-kappa B (NF-κB) inhibited the high expression of IL-1β and TNF-α in liver tissue and slowed down the down-regulation of CYP2E1 metabolism and protein expression. Conclusions NF-κB may be involved in the regulation of CYP2E1 by regulating the inflammatory cytokines IL-1β and TNF-α.

Full text: Available Index: WPRIM (Western Pacific) Type of study: Prognostic study Language: Chinese Journal: Chinese Pharmacological Bulletin Year: 2019 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Type of study: Prognostic study Language: Chinese Journal: Chinese Pharmacological Bulletin Year: 2019 Type: Article