Pregabalin, a GABA Analogue Protects against Carbon Tetrachloride-Induced Oxidative Stress and Liver Injury in Rats

Authors

  • Omar M.E. Abdel-Salam Department of Toxicology and Narcotics, National Research Centre, Cairo, Egypt
  • Eman R. Youness Department of Medical Biochemistry, National Research Centre, Cairo, Egypt
  • Fatma A. Morsy Department of Pathology, National Research Centre, Cairo, Egypt
  • Amany Ameen Sleem Department of Pharmacology, National Research Centre, Cairo, Egypt

DOI:

https://doi.org/10.20455/ros.2021.r.805

Keywords:

Carbon tetrachloride; Glutathione; Hepatoprotection; Lipid peroxidation; Liver damage; Nitric oxide; Oxidative stress; Pregabalin

Abstract

Pregabalin is a synthetic analogue of the neurotransmitter g-aminobutyric acid (GABA) and is used in the treatment of epilepsy and neuropathic pain. The aim of this study was to investigate the effect of pregabalin on toxic liver injury caused by the acute administration of carbon tetrachloride (CCl4). Rats were orally treated with CCl4 for two successive days either alone or along with intraperitoneal pregabalin at doses of 7 and 14 mg/kg. The control group received the vehicle (olive oil). Liver oxidative stress and damage were assessed by determining serum and/or liver tissue levels of malondialdehyde (MDA), nitric oxide (NO), reduced glutathione (GSH), DNA fragmentation, serum aminotransferases, paraoxonase-1 (PON-1), and hepatic histopathology. Results showed that CCl4 significantly (i) increased MDA and NO and decreased PON-1 in both serum and liver tissue, and (ii) decreased liver GSH content and induced marked hepatic DNA fragmentation. CCl4 treatment caused liver tissue injury as evidenced by significantly increased serum aminotransferases. In line with the above biochemical changes, the liver of CCl4-treated rats exhibited massive steatosis, vacuolar degeneration, cloudy swelling, and necrosis. In CCl4-treated rats, pregabalin given at the dose of 14 mg/kg significantly reduced the increments in MDA, NO, serum aminotransferases, and hepatic DNA fragmentation. Liver GSH was unaltered but hepatic and serum PON-1 activity increased after administering pregabalin which also improved, though not normalized, liver tissue histopathology. Collectively, these results suggest that the administration of pregabalin is associated with a reduction in experimental liver injury caused by CCl4.

(First online: Apr 12, 2021)

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Published

2021-04-12

How to Cite

Abdel-Salam, O. M., Youness, E. R. ., Morsy, F. A. ., & Sleem, A. A. . (2021). Pregabalin, a GABA Analogue Protects against Carbon Tetrachloride-Induced Oxidative Stress and Liver Injury in Rats. Reactive Oxygen Species, 11, r23–r33. https://doi.org/10.20455/ros.2021.r.805

Issue

Section

ORIGINAL RESEARCH