CYP24A1 and CYP3A4 Levels, Renal, Hepatic Changes, and Incidence of Oxidative Stress in Tramadol-Alcohol Concomitant Misuse.

Abstract

Introduction Long-term population-based research has demonstrated a link between heavy drinking and the prevalence of kidney disorders; similarly, alcohol abuse has long been recognized as one of the main causes of liver diseases. A recent trend of concomitant use of the opioid analgesic Tramadol and alcohol amongyoung males in sub-Saharan Africa has emerged. Aim and objectives This study's primary aim was to evaluate the incidence of concomitant use of alcohol and Tramadolamong adult males, and observe the role ofcytochrome p450 3A4 and CYP24A1 proteins and some oxidative stress indicators such as Malondialdehyde, lactate dehydrogenase, among study participants. The secondary aim was to evaluate the effect of alcohol and Tramadol concomitant use on Liver and kidney indices. Methods Our study population was male subjects with a history of Alcohol and Tramadol concomitant use. Liver enzymes, renal indices, oxidative stress markers, and CYP3A4 and CYP24A1were determined from the serum of test and control participants. IBM Statistical Package for Social Sciences (SPSS) Statistics (version 21.0) was used to analyze the data obtained. Result One hundred and forty-two male subjects were included in this study. Eighty two (82) were males who admitted to abuse of Alcohol and Tramadol concomitantly for at least a year. The dose of Tramadol commonly used by Test subjects was 200 mg (43.9% of the test population), Tramadol users in the study population were largely Undergraduates (75.6% of Test participants). Gamma-glutamyl transferase and lactate dehydrogenase were significantly higher in Test subjects consuming Tramadol and alcohol combination (43.13±1.02 and 117.29±2.45, respectively) versus control (24.87±0.82; p=0.00 and 101.93±1.25; p=0.00). There was a significant decrease in serum bicarbonate levels of Test subjects (16.19±0.53) versus control (22.60±0.68; p=0.000). Cytochrome P450 24A1, was significantly lower in Test subjects (subjects consuming Tramadol and alcohol combination) (0.90±0.06; p=0.01), and significantly threefold higher in subjects with acute myeloid leukemia (AML) (5.16±0.5; p=0.00), when compared with values of non-drug/alcohol users that served as normal control (1.27±0.07). Conclusion The menace of Tramadol and alcohol concomitant abuse has taken a worrisome dimension in sub-Saharan Africa. In this study 77.4% of participants reported euphoria as reason for combining Alcohol and Tramadol, 6.5% claimed it was for faster pain relief and enhanced sexual performance or prolong penile erection was the response of 58.1% of the test participants. Findings of reduced CYP3A4 with Alcohol and Tramadol concomitant use could be associated with delayed drug inactivation and increased drug euphoric action.