The Effect of Tramadol on the Liver of Rats and the Curative Role of Vitamin E: Histological and Histochemical Studies
Mohammed S. Gabry 1, Abdel Razik H. Farrag2 and Sara I. Hassan*1
1 Zoology and Entomology Department, Faculty of Science, Helwan University,
2 Pathology Department, National Research Centre
Histopathological and histochemical changes in liver of male albino rats due to the effect of the Tramadol (analgesic narcotic opioid drug) and the curative effect of vitamin E (antioxidant) were investigated. There were seven groups of experimental laboratory animals (albino rats), the first was served as control. The other three groups were orally given (30 mg/kg/day) of Tramadol for one, two, and three weeks. Later three groups were orally given (30 mg/kg/day) of Tramadol and (9 mg/kg/day) of vitamin E for one, two, and three weeks. The Histopathological examination of liver in treated rats with tramadol showed inflammatory cellular infiltration, hydropic degeneration, dilatation of blood sinusoids, pyknotic nuclei. On the other hand, the histochemical investigations of liver in groups treated with Tramadol showed gradually decrease the carbohydrate and protein content in hepatic cells. Examination of liver tissues in rats treated with Tramadol and vitamin E showed tissue improvement, and increase in the amount of carbohydrate and protein contents of hepatic cells as compared with the others treated with Tramadol only. These improvements were in duration dependent. It was concluded that co-administration of vitamin E with Tramadol caused amelioration of the injury that induced by Tramadol.
Tramadol (1RS, 2RS) -2 [(dimethyl amino) methyl]-1- (3-methoxyphenyl) - cyclohexanol) is a synthetic opioid, an analgesic with opioid agonist properties that acts on the neurotransmission of noradrenalin and serotonin (Hennies et al., 1988; Raffa et al., 1992; Collart et al., 1993; Leppert, 2009) Tramadol is rapidly and extensively metabolized in the liver. The main metabolic pathways, O- and N - demethylation, involve cytochrome P-450 (Bressollel et al., 2009). These metabolites are active substances and more potent (2 to 4 times ) than Tramadol itself (Wu et al., 2001; Tao et al., 2002; Atici et al, 2005). The metabolic activation by P-450 plays a pivotal role in the hepatotoxicity and in the immune-toxicity (Pacifici et al., 2003) through the generation of reactive oxygen species and peroxidative stress (Boelsterli et al., 1991; Devi et al., 1996; O¨ ztezcan et al., 2000; Pacifici et al., 2003). Atici et al. (2005) suggest the possible hepatotoxic effects Tramadol in long term. Vitamin E (α-tocopherol) has been recognized as being the major lipid-soluble, chain breaking anti-oxidant that prevents free radicals from initiating peroxidative tissue damage (Verma et al., 2007). Several studies have also shown that α-tocopherol inhibits free radical formation (Kalender et al., 2004; Kalender et al., 2005) and may effectively minimize lipid peroxidation in biological systems (Kalender et al., 2002; Kalender et al., 2010). Therefore, this study aimed to inve-stigate the curative effect of vitamin E against Tramadol-induced liver injury in rats. MATERIAL AND METHODS
1-Chemicals: Only the therapeutic dose of Tramadol was obtained from Grunenthal, Germany pharmaceutical company in the form of tablets (200 mg). Vitamin E was obtained from Pharco pharmaceutical company in the form of capsules (400 mg) for the present study.
1.1-The therapeutic dose of Tramadol was estimated to be 30 mg/kg/day. Tramadol tablets (200 mg) were diluted with saline 0.9% Nacl to obtain the used concentration.
1.2-The therapeutic dose of vitamin E was estimated to be 3.6 mg/kg/day. Vitamin E capsule (400 mg) was diluted with sesame oil to obtain the concentration used.
2-Experimental animals: Healthy adult male albino rats...