ABSTRACT
Abuse of alcohol and some analgesic such as tramadol has attained a worrisome dimension, with cocktail of alcohol combined with tramadol being consumed by young adults in Nigeria. The prohibition of Tramadol sale may have propelled the use of other analgesics such as diclofenac. Therefore, the present study aimed at evaluating the effect of alcohol, diclofenac and tramadol combinations on the liver and kidney of albino wistar rats and the combine protective effect of Grape and Pawpaw Seed extract, as well as the effect of alcohol-tramadol combination in human subjects. One hundred and fifteen (115) wistar rats were obtained and divided randomly into groups of six rats each and each group treated for 90 days with 5% alcohol, 45% alcohol, 45% alcohol and 2mg/kg diclofenac, 45% alcohol and 20mg/kg of tramadol. Some groups were treated with 45% alcohol and tramadol or diclofenac with grape seed and/or pawpaw seed extracts concomitantly. To observe this pattern in humans, one hundred and forty two (142) male participants from age 19 to 30 years were recruited from clubhouses and bars where alcohol is usually sold. These were males who admitted to alcohol-tramadol abuse. Electrolytes, urea, creatinine, liver function test and haematological analysis were analysed in blood samples of rats and humans, while Malondialdehyde, Cytochrome p450 24A1, Cytochrome p450 3A4, antioxidants such as reduced glutathione, catalase and superoxide dismutase, were analysed in liver and kidney homogenates of rats. The result of this study revealed marked % weight gain in rats administered Grape seed and pawpaw seed extracts (10.6%), 5% Alcohol (10.4%), Grape seed & Unripe Pawpaw Seed Extract with 45% Alcohol and Tramadol by peritoneal route (13.6%) in in comparison with 6.8% weight gain in control rats. Marked % weight loss was recorded for rats treated with Tramadol 20 mg/kg (-7.9%) and rats given 45% Alcohol and Tramadol combination ( 10.5%). In comparison with control (5.8 ± 1.0), there was significant increase in white blood cell count for rats treated with 45% Alcohol and Tramadol (10.5 ± 3.9), and in rats given Grape Seed Extract with 45% Alcohol and Tramadol (16.5 ± 5.1) (p = 0.00; f-value = 4.19). Serum bicarbonate was significantly decreased in rats given 5% Alcohol and Tramadol orally (3.7±2.3), and rats given 45% Alcohol and Tramadol orally (4.0±3.2) in comparison with control rats (18.3 ± 4.3) (p=0.00; f-value= 24.01). There was significant decrease in reduced glutathione levels, catalase and superoxide dismutase levels, which was significantly ameliorated by grape seed and pawpaw seed extracts. Elevated Cytochrome 24A1 protein level was recorded with chronic administration of 45% alcohol in rats (10.4 ng/ml), while it was significantly decreased with 45% alcohol and diclofenac combination (2.6 ng/ml). This study was able to establish that hepatotoxicity and nephrotoxicity are associated with alcohol and tramadol concomitant use, as well as unravel the protective potentials of grape seed and pawpaw seed extracts both separately and combined. Although mild to moderate use of 5% alcohol showed antioxidant benefits, the chronic use of 45% alcohol with or without drugs should be avoided.