Volume 16, Issue 38, July - December, 2022

The effect of high doses of the slimming agent 2,4 dinitrophenol in the rat brain: A biochemical and histopathological study

Omar ME Abdel-Salam^1♦, Dalia Medhat², Fatma A Morsy³, Marwa E Shabana³, Noha N Yassen³, Amany Ameen Sleem⁴

¹Department of Toxicology and Narcotics, Medical Research and Clinical Studies Institute, National Research Centre, Cairo, Egypt
²Department of Medical Biochemistry, Medical Research and Clinical Studies Institute, National Research Centre, Cairo, Egypt
³Department of Pathology, Medical Research and Clinical Studies Institute, National Research Centre, Cairo, Egypt
⁴Department of Pharmacology, 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, Cairo, Egypt

ABSTRACT

The uncoupler of mitochondrial oxidative phosphorylation 2,4 dinitrophenol (2,4-DNP) is used as a weight reducing agent and there are reports of toxicity and deaths due to the agent. We aimed to examine the effects of high doses of 2,4-DNP on brain in rats. 2,4-DNP was intraperitoneally injected at doses of 10, 40, 80 and 160 mg/kg and rats euthanized 4h later. Markers of oxidative stress including lipid peroxidation (malondialdehyde), reduced glutathione and nitric oxide were measured. In addition, paraoxonase-1 (PON-1) and butyrylcholinesterase (BCHE) activities were determined. Histopathological changes were evaluated using of haematoxylin and eosin staining. Periodic acid Schiff’s (PAS) staining for mucopolyssacharides and immunostaining for cleaved casapase-3. Results showed that 2, 4-DNP caused inhibition of lipid per oxidation, nitric oxide and depletion of reduced glutathione. There were also inhibition of brain PON-1 and BCHE activities. The histopathological study revealed brain spongiform degeneration by 10 mg/kg 2,4-DNP while extensive neuronal necrosis and aggregates of focal gliosis occurred after the higher doses. There were also increased PAS reaction and cleaved caspase-3 immunostaining. Collectively, these results indicate deleterious effects for high doses of 2,4-DNP on brain tissue which is caused by uncoupling of mitochondrial oxidative phosphorylation and cellular energy depletion.

Keywords: 2,4-dinitrophenol, oxidative stress, mitochondrial uncoupling, apoptosis.

Drug Discovery, 2022, 16(38), 94-103

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