Paracetamol Overdose Induces Acute Liver Injury accompanied by oxidative stress and inflammation

Ahmed, Hend Mostafa; Shehata, Hanan Hussein; Mohamed, Gamila Soliman; Abo-Gabal, Hoda Hassan; El-Daly, Sherien M.

doi:10.21608/ejchem.2022.140587.6153

Paracetamol Overdose Induces Acute Liver Injury accompanied by oxidative stress and inflammation

Document Type : Original Article

Authors

¹ Medical Biochemistry Department, Faculty of Medicine, Ain Shams University

² Professor of Medical Biochemistry and Molecular Biology Faculty of Medicine- Ain Shams University

³ Professor of Medical Biochemistry National Research Centre

⁴ Assistant Professor of Pathology Faculty of Medicine- Ain Shams University

⁵ Associate Professor of Medical Biochemistry National Research center

10.21608/ejchem.2022.140587.6153

Abstract

The concept of paracetamol as a safe drug has become very misleading as this has led to a high rate of paracetamol toxicity. Hepatotoxicity and liver failure have been reported even with doses just more than the maximum therapeutic dose, which was obviously noticed in the (COVID-19) pandemic. Oxidative stress plays an important role in paracetamol hepatotoxicity. The current study investigates the mechanism of action through which paracetamol induces hepatotoxicity and implements an alarming sign for the unsupervised use of paracetamol. Twenty albino rats were equally divided into a normal control group and paracetamol treated group where rats received paracetamol at a dose of 2g/kg b.wt once orally for 24 hours. Oral administration of paracetamol resulted in a significant elevation of liver enzymes in serum such as glutamate pyruvate transaminase and glutamate oxaloacetate transaminase when compared with the results of the control group. In terms of oxidative stress biomarkers, the group that received an overdose of paracetamol showed a significant increase in the tissue level of 4-Hydroxynonenal accompanied by a significant decrease in the activity of the anti-oxidant markers Paraoxonase and Catalase. Histopathological examination revealed focal necrosis in the hepatocytes, Centri-lobular necrobiotic changes, and dilated congested portal vein. Immunohistochemical investigation for the Nuclear factor-kappa B showed strong positive expression in the nuclei of the hepatocytes of rats that received an overdose of paracetamol. Our study suggests that an overdose of paracetamol could attenuate the endogenous antioxidant defense mechanisms and augment the hepatic tissue inflammation; both factors may contribute to the observed increase in apoptosis-related signaling and cell death.

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