Abstract
The present study investigated the effects of repeated tramadol administration on 60 male rats. The animals were randomly divided into 6 equal groups (n=10/group). The first group served as control and received saline solution only during the study. the second, third, fourth , fifth and sixth groups were given oral doses of tramadol ( tramadol HCL) suspended in saline solution equal to 40, 80, 120,160 and 200 mg/kg daily for 60 days. Liver and kidney functions, sex hormones activity, some neurochemical parameters in addition to some histopathological changes of the rat testis and brain tissues were studied. The results of the present experiment revealed a significant gradual increase in the serum ALT, AST and creatinine by increasing the dose of tramadol, the same result was obtained for PRL and E2 in male rats. Tramadol significantly reduced serum LH, FSH and testosterone levels gradually, where 200 mg/kg showed the lowest levels. Repeated administration of tramadol also increased the density of α1–adrenoceptors in the rat brain cortex, as measured by saturation analysis of [3H]prazosin binding resembling the effects induced by conventional antidepressants. The histopathological examination of testis revealed severe diffused testicular degeneration, which was aggravated till testicular tissues calcification with increasing dose of tramadol (40, 80, 120, 160 and 200 mg/ kg.b.wt.). Brain tissues in all treated groups showed slight congestion of sub-meningeal blood vessels and neural degeneration. These findings suggest increased hepatic, renal and neurological damage and sexual dysfunction evoked by repeated administration of tramadol for long periods.
Highlights
Tramadol is a synthetic opioid analgesic commonly prescribed for moderate to severe pain, with doses up to 200 mg/day (McKeon et al, 2011)
Biochemical analysis 1- Liver, kidney function parameters and sex hormones activities: -Aminotransferases (ALT, AST) activities were measured using the method of (Thomas, 1998). -Creatinine was determined using the method of Fossati et al, (1983). -Luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL), testosterone (Tes) and estradiol (E2) were determined using enzyme linked immunosorbant assay (ELISA) kits according to manufacturer instructions. 2- α1-adrenoceptors binding in the rat brain cortex
Histopathological study Specimens collected from brain and testis were fixed in phosphate buffered formalin, used for preparation of sections, stained with hematoxylin and eosin (H&E), and processed for histopathological examination using light microscope according to Bancroft and Gamble (2002)
Summary
Tramadol is a synthetic opioid analgesic commonly prescribed for moderate to severe pain, with doses up to 200 mg/day (McKeon et al, 2011). The aim of the present study was to assess, the biochemical, pharmacological and histopathological toxicity profiles of Tramadol HCl. Liver and kidneys functions, sex hormones activity and some neurochemical parameters were studied on male rats and brain and testis tissues were subjected to histopathological analysis. Animals and dosing The experiment was carried out on 60 male rats weighing 180-200 g, obtained from the animal research unit of the faculty of veterinary medicine, Zagazig University. All animals were housed in a quiet non-stressful environment for 10 days before study, they were given normal rat chow and water ad-libitum throughout the experiment. Histopathological study Specimens collected from brain and testis were fixed in phosphate buffered formalin, used for preparation of sections, stained with hematoxylin and eosin (H&E), and processed for histopathological examination using light microscope according to Bancroft and Gamble (2002). The statistical method was one way ANOVA test followed by LSD
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