Research Article Open Access Essam Hafez et al., J Alcohol Drug Depend 2015, 3:5 DOI: 10.4172/2329-6488.1000225 Research Article Open Access Volume 3 • Issue 5 • 1000225 J Alcohol Drug Depend ISSN: 2329-6488 JALDD, an open access journal Parenchymatous Toxicity of Tramadol: Histopathological and Biochemical Study Essam Hafez M 1* , Sahar Issa Y 2 and Safaa Abdel Rahman M 3 1 Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Minia University, Egypt 2 Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Alexandria University, Egypt 3 Central Laboratory, Alexandria, Egypt Abstract Objective: The present study was designed to highlight the toxic impact of tramadol on both biochemical and histopathological aspects in rats' liver, kidney and thyroid gland. Methods: The study was performed on ffty healthy adult male albino rats divided into fve groups with ten rats each. (Four experimental and control groups). Five rats (negative control) were kept in a quite non stressful environment, provided with food ad libitum and free access to water. Normal saline (1 ml) was given intramuscularly as placebo in the positive control group (n = 5). Experimental groups (II, III, IV and V) were injected with tramadol intramuscularly equivalent to 12.5 mg, 25mg, 50 mg and 300 mg/kg body weight/day respectively for two weeks. Results: The levels of alanine aminotransferase (ALT), Cardiac treponin I (CTnl), Prothrombin time (PT) and partial thromboplastin time (PTT) in all tramadol treated groups showed signifcant elevation when compared to control. As regards thyroid function tests (T3, T4, and TSH) showed no signifcant laboratory difference between all studied groups. There was hepatic and renal histopathological changes in tramadol treated rats whose severity varied with doses of tramadol given. Histopathological changes in thyroid tissues were only seen in group treated with tramadol 50 mg/kg and in acute toxicity group. Conclusion and recommendation: Toxic effects of tramadol on parenchymatous organs as liver, kidney and thyroid gland should be kept in mind and taken cautiously in patient complaining from heaptorenal affection or thyroid diseases. Keywords: Tramadol; Hepatic; Renal; Tyroid; Biochemical; Histopathology Introduction Opioids are used as analgesics and considered efective for the treatment of acute cancer and non-cancer chronic pain [1]. Analgesics are among the most popular drugs which are being abused [2]. Tramadol is a synthetic, centrally acting analgesic, available in Europe since 1977 and in the United States since 1995 for the treatment of pain syndromes previously amenable only to the opiate analogues [3]. It has dual mode of action. Its analgesic efcacy is attributed to its partial afnity for the mu- opiate receptor and its inhibition of norepinephrine and serotonin reuptake [4]. Tramadol is converted in the liver to O-desmethyl-tramadol by cytochrome P 450 which itself is an active substance and is two to four times more potent than tramadol. Further, biotransformation results in inactive metabolites, which are excreted through kidneys [5]. Every drug has been associated with hepatotoxicity almost certainly due to the pivotal role of the liver in drug metabolism. Metabolites of the drugs that are excreted from kidneys may also cause cellular damage leading to kidney dysfunction [6]. High-dose glucocorticoids, high-dose dopamine and potent opioids (e.g. tramadol) inhibit thyroid stimulating hormone (TSH) release and therefore may decrease the TSH concentration [7]. Aim of the Work Te present study was designed to highlight the toxic impact of tramadol on both biochemical and histopathological aspects on rats’ liver, kidney and thyroid gland. Materials and Methods Animals Fify healthy adult male albino rats weighting about 150-170 grams were obtained from the animal house in faculty of science Minia University. All animals were allowed free access to distilled water and laboratory chow ad libitum. To avoid stress of isolation or overcrowdings, 6 rats were housed per cage. Tey were lef freely wandering in their cage for two weeks with 12 hour dark to light cycle for acclimatization before starting the experiment. Experimental procedures were performed in accordance with the guide of the care and use of laboratory animals approved by the committee of Minia University, the fewest number of animals estimated to obtain valid results were used and painful procedures were conducted with appropriate sedation to avoid pain and stress. Drug Tramadol HCl 100 mg/ 2ml /ampoule, Alexandria Company for pharmaceutics.All doses of tramadol were delivered in a volume of 1 ml *Corresponding author: Essam Mahmoud Hafez, Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Minia University, Egypt, Tel: +00966-545-990-785; E-mail: essamtox@yahoo.com Received: October 08, 2015; Accepted: October 27, 2015; Published: October 31, 2015 Citation: Essam Hafez M, Sahar Issa Y, Safaa Abdel Rahman M (2015) Parenchymatous Toxicity of Tramadol: Histopathological and Biochemical Study. J Alcohol Drug Depend 3: 225. doi:10.4172/23296488.1000225 Copyright © 2015 Essam Hafez M, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Journal of Alcoholism & Drug Dependence J o u r n a l o f A l c o h o li s m a n d D r u gD e p e n d e n c e ISSN: 2329-6488