Volume 17, Issue 39, January - June, 2023

Liver toxicity produced by the weight reducing agent 2,4 dinitrophenol

Omar ME Abdel-Salam^1♦, Fatma A Morsy², Dalia Medhat³, Noha N Yassen², Marwa E Shabana²

¹Department of Toxicology and Narcotics, Medical Research and Clinical Studies Institute, National Research Centre, Cairo, Egypt
²Department of Pathology, Medical Research and Clinical Studies Institute, National Research Centre, Cairo, Egypt
³Department of Medical Biochemistry, Medical Research and Clinical Studies Institute, National Research Centre, Cairo, Egypt

^♦Corresponding author
Department of Toxicology and Narcotics, Medical Research and Clinical Studies Institute, National Research Centre, Tahrir St., Dokki, Cairo, Egypt

ABSTRACT

Drug induced liver disease is an important and serious clinical problem. In this study, the effects of administering high doses of the sliming agent 2,4-DNP (2,4- DNP) on the rat liver was examined. Rats received intra peritoneal injections of 2,4-DNP (10, 40, 80, and 160 mg/kg) and euthanized after 4h. Measurements of malondialdehyde (lipid peroxidation) and reduced glutathione were done. Liver injury was evaluated by histopathology. Cell apoptosis was assessed by cleaved casapase-3 immunostaining. Masson's trichrome staining and liver hydroxyproline content were used to quantify collagenous fibers. Tissue content of mucopolysaccharides was assessed by the Periodic acid Schiff's (PAS) stain. Results showed that rats treated with 2,4-DNP exhibited significant inhibition of lipid peroxidation and marked decrease in reduced glutathione liver tissue levels. Severe liver injury occurred after 2,4-DNP indicated by liver inflammatory cell infiltrations and pyknotic hepatocytes progressing as the dose increased to massive degenerative changes, fibrosis and ultimately focal coagulative necrosis. There were also increased liver collagen and mucopolysaccharide contents. In addition, 2,4-DNP caused marked increments in cleaved caspase-3 expression in the liver. These results showed that high doses of the weight reducing agent 2,4- DNP can inflict serious liver injury as a consequence of uncoupling of oxidative phosphorylation and depletion of energy stores.

Keywords: Mitochondrial uncoupling, 2,4-dinitrophenol, weight loss, hepatic toxicity, apoptosis, necrosis

Drug Discovery, 2023, 17(39), e2dd1002

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DOI: https://doi.org/10.54905/disssi.v17i39.e2dd1002

Published: 16 January 2023