Neurotoxic, Hepatotoxic and Nephrotoxic Effects of Tramadol Administration in Rats
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Neurotoxic, Hepatotoxic and Nephrotoxic Effects of Tramadol Administration in Rats Haytham A. Ali 1,2 & Mohamed Afifi 1,2 & Taghred M. Saber 3 & Arwa A Makki 1 & A.T. Keshta 4 & Mohammed Baeshen 5 & Ammar AL-Farga 1 Received: 17 March 2020 / Accepted: 13 May 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract The current study was performed to study the tramadol HCL toxic effects on the brain, liver, and kidney of adult male rats. Forty male adult albino rats were divided into 4 groups; the first one was considered as a control group, the others were orally administrated with 25, 50, and 100 b.wt. representing therapeutic, double therapeutic, and 4 times therapeutic doses, respectively, of tramadol HCL daily for 1 month. Serum and brain, hepatic, and renal tissues were collected for biochemical and molecular investigations. Tramadol HCL resulted in a significant increase in the brain serotonin, 8-hydroxy-2′-deoxyguanosine (8-OHdG), and malonyldialdehyde (MDA) levels with a significant decrease in the reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) activities. At the same line, hepatic and renal 8-OHdG and MDA levels showed a significant increase with a significant decrease in reduced glutathione (GSH), CAT, and SOD activities. In addition, hepatic and renal function parameters including serum alanine amino transferase (ALT), aspartate amino transferase (AST), urea, and creatinine were increased in a dose-dependent manner. At the molecular levels, hepatic cytochrome P5402E1 (CYP2E1), renal Kidney Injury Molecule-1 (KIM-1), and tissue inhibitor of metalloproteinase-1 (TIMP-1) showed also a significant increase in the expression levels. Histopathological evaluation of the brain confirmed the above biochemical results. In conclusion, tramadol HCL induced neurotoxic, hepatotoxic, and nephrotoxic effects in a manner relative to its concentration by affecting brain serotonin levels and hepatic and renal function, with the production of DNA damage and oxidative stress. Keywords Serotonin . KIM-1 . 8-OHdG . TIMP-1 . Tramadol HCL . CYP2E1
Introduction Tramadol is a centrally acting synthetic opioid analgesic, which is utilized to treat moderate or severe pain (Pinho et al. 2013). Tramadol exerts its analgesic effect as a result of inhibiting the serotonin and norepinephrine reuptake and binding the μopioid receptors (Gillman 2005; Grond and Sablotzki 2004). * Haytham A. Ali [email protected] 1
College of Science, Department of Biochemistry, University of Jeddah, Jeddah, Saudi Arabia
2
Department of Biochemistry, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, Egypt
3
Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, Egypt
4
Department of Biochemistry, Faculty of Science, Zagazig University, Zagazig 44519, Egypt
5
College of Science, Department of Biology, University of Jeddah, Jeddah, Saudi Arabia
The abuse of tramadol could lead to serotonin syndrome (SS), a dangerous conditi
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