Comparative Study on the Biochemical Effects of Gin and Lager Beer, and their concomitant Administration with Tramadol in Wistar Rats.

Received: 13-May-2025;Accepted Date: May 06, 2025; Editor assigned: 15-Apr-2025 Reviewed: 29-Apr-2025 Revised: 06-May-2025 Published: 12-May-2025, DOI: 10.4303/JDAR/236450

Introduction

Tramadol is a synthetic opiate drug primarily used in treating mild to severe pain. It causes the onset of pain relief within an hour by acting as an analgesic with dual mechanism of action [1]. First, it binds to the μ-opioid receptor and second by inhibiting the reuptake of serotonin and norepinephrine which are important factors (neurotransmitters) in regulating mood, sleep as well as pain, behaviours as well as how individuals react to stress and anxiety. Through this mechanism, it can modulate the descending pain pathways within the central nervous system by allowing the binding of its metabolite to μ-opioid receptors and the weak inhibition of the reuptake of norepinephrine and serotonin [2].

Its consumption medically is considered relatively safe as a medicinal drug with a low potential for dependence relative to morphine. However, its overuse from weeks to months may result in its dependence even when used in the recommended dose [3].

At higher doses and rarely at therapeutic doses, intoxications may occur, with symptoms similar to those of other opioid analgesics but may include serotonergic and noradrenergic components such as Central Nervous System (CNS) depression and coma, tachycardia, cardiovascular collapse, seizures, and respiratory depression up to respiratory arrest. Fatal intoxications are rare and appear to be associated with large overdoses of tramadol or when co-ingested with other drugs and substances including alcohol [4].

Alcohol consumption while taking opiate drugs like tramadol alters the rate of absorption and distribution of the drug [5]. High doses of tramadol and drinking alcohol may increase the absorption rate of the tramadol and thus increase its central nervous system depressant effects [5]. In fact, most tramadol overdose occurs when the drug is combined with alcohol or used alongside other drugs [6]. Alcohol intake with tramadol may lead to severe liver damage and seizures. This method of tramadol usage in higher doses has also been linked to the risk of suicide among individuals who consume alcohol heavily [7].

Tramadol and alcohol both act as central nervous system depressants, with the ability to slow down brain function, breathing and heartbeat rate. Mixing both increases the calming and euphoric effects of both substances on the brain and other organs that participate in their breakdown and excretion [6]. Apart from liver and kidney damage, other recorded effects of mixing alcohol and tramadol include drowsiness, dizziness, sleepiness, loss of balance and coordination, nausea and vomiting, memory problems, elevated heart rate, coma and death [8].

Alcohol interferes with the brain’s communication pathways and can affect the structure and function of the brain. This disruption can change mood and behaviour and make it harder to think clearly and move with coordination. It changes the chemical that breaks down and removes scar tissue, causing a build-up of scars in the liver, which can lead to liver dysfunction or complete failure in its function [3].

This failure then prevents the ability of the liver to break down drugs including tramadol into extractable forms, and their accumulation results in hepatoxicity and elevated transaminases reported in tramadol abuse during alcohol consumption.

Methodology

Collection and preparation of materials

A bottle of GINMG (43% v/v alcohol) was obtained from Spar shopping mall Calabar, Nigeria, and Budweiser lager beer (5% Alcohol), obtained from Coslow store along MCC road Calabar, were used as an alcoholic beverages. While tramadol (50 mg) was obtained with prescription from Maxicare pharmacy, Calabar.

Laboratory animals

Twenty-four (24) male Wistar rats weighing between 83.24 g to 118.92 g were obtained from the animal house of the College of Medical Sciences, University of Calabar. The animals were housed in aluminum cages in the animal house, and fed with rat chow and tap water ad libitum. The animals were acclimatized for seven days, and their weights were noted before the commencement of experimental treatment.

Drug administration

The twenty-four rats were divided into six groups of four rats each. Group one served as the normal control and received 0.5 ml of water, group two received tramadol (1.43 mg/kg body weight), group three was given alcoholic beverage (gin) (3.57 ml/kg body weight), group four received alcoholic beverage (lager beer) (3.57 ml/kg body weight), group four was given tramadol (1.43 mg/kg body weight)+alcoholic beverage (gin) (3.57 ml/kg body weight) and group five received tramadol (1.43 mg/kg body weight)+alcoholic beverage (lager beer) (3.57 ml/kg body weight) once daily for 21 days.

Collection and preparation of tissues for analysis

At the end of the 21 days, the animals were fasted overnight and anaesthetized using ketamine. They were then dissected and their blood collected with sterile syringes via cardiac puncture. The blood was divided into two fractions; one into heparinized screw-cap bottles for haematological analysis, while the second fraction was collected into plane screw-cap bottles for biochemical analysis. Sample in the plane tubes were allowed to stand for two hours for clothing to take place. The samples were centrifuged at 3000 rpm for 10 minutes using an MSE1519 France tabletop centrifuge. Serum was collected using a semi-automatic pipette into labelled specimen tubes. The serum was stored in a refrigerator until when required for analysis. The storage period, however, did not exceed 48 hours.

Data analysis

Data obtained were analyzed using one-way Analysis of Variance (ANOVA) and the Turkeys HSD posthoc test to compare each of the test groups with the control group as well as, to compare the test groups for any significant difference in the effect of the treatment on the various parameters using SPSS package with significant level at (P <0.05).

Results and Discussion

Alcohol abuse is a growing epidemic in Nigeria, especially among men and it is becoming a major problem among young adults. The clinical manifestations of alcohol-induced hematologic disorders are profoundly influenced by the patient’s social and economic status and the presence or absence of other factors, such as nutritional deficiency or alcoholic cirrhosis. Most of the studies have shown potential deleterious effects of tramadol and alcohol on the liver, kidney, haematological profile and many other biochemical parameters when administered singly.

Effects of tramadol and alcohol on percentage growth rate and percentage body weight increase (%)

The weight of the rats after 21 days of administration of tramadol and alcoholic beverages (gin and lager beer) were obtained and compared with the initial weight measured before each treatment. The differences in weights were used to determine the percentage weight increase and growth rate during this period (Table 1).

Note: Value are expressed as mean ± SEM, n=6; * =significantly different from group 1 at p<0.05.

Table 1: Growth rate and body weight increase of the different experimental group.

The value of the percentage body weight decreased significantly (p<0.05) in the tramadol group (1.13 ± 4.17), gin group (12.34 ± 1.84*), lager beer treated group (4.10 ± 1.84) and tramadol+lager beer treated group (-16.73 ± 2.18), tramadol+ gin group (14.79 ± 0.51*, a) compared to the control group (35.89 ± 7.10). Our results agreed with the report [9], of those who report a lack of clear trend between short-term alcohol consumption and weight gain. However, we observed a general decrease in the tramadol and alcohol beverages treated groups compared to the normal control. While the gin and gin+tramadol treated groups showed an increase in body weight when compared to tramadol and lager beer+tramadol treated groups. The result also showed a significant (p<0.05) decrease in the body weight when compared to alcohol treated groups. Tramadol has been reported to significantly decrease the body weight in obese patients [1].

Percentage growth rate decreased significantly (p<0.05) following a similar pattern with the body weight with the groups treated with tramadol (6.52 ± 23.63), lager beer (30.38 ± 12.54), gin (69.84 ± 10.39*), tramadol+gin (84.16 ± 3.04*, a) and tramadol+lager beer (-90.40 ± 11.82) compared to the control group (156.29 ± 21.87). However, the link between tramadol and alcoholic beverage consumption and growth is not yet clear.

Effects on serum total protein, albumin and globulin concentrations

Serum total protein, albumin and globulin decreased significantly (p<0.05) in the tramadol-treated group compared to the control group. There were significant decreases (p<0.05) in the gin, lager beer, tramadol+gin and tramadol+ lager beer treated groups compared to the control group, as reported in Table 2. In this study, we observed that the total protein and globulin concentrations were significantly higher compared to albumin concentration in the gin-treated group with values of 75.83 ± 0.79*, a and 35.83 ± 0.87*, a respectively, when compared to other groups, including the control group. The second group with elevated values of total protein and globulin was the tramadol+gin-treated group when compared to albumin concentration, as shown in Table 2. However, we observed statistically significant negative correlation between tramadol and tramadol+lager beer treated groups and serum albumin concentrations in this study. This agreed with the report of changes in the total protein [10, 11], albumins and globulin in patients with alcoholism history of hypoalbuminemia and hyperglobulin and total protein levels. However, the link for these changes in the concentration remains unclear suggesting the intake of tramadol and lager beer could have more health consequences compared to taking gin+tramadol.

Note: Value are expressed as mean ± SEM, n=6; * =significantly different from group 1 at p<0.05.

Table 2: Protein concentration (g/l).

Effects on hepatic enzymes: Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (ALP) Concentration (IU/L)

The proteins AST, ALT and ALP are cellular enzymes which are released into the bloodstream on cell injury. These serve as indicators of liver injury. They could rise to as high as 300 IU/L and beyond in serious liver diseases or damages including hepatitis and cirrhosis. Elevated levels of these enzymes are also been observed in alcohol liver damage [11]. Excessive alcohol consumption can cause liver diseases including fatty liver, hepatitis and cirrhosis [12]. Since alcohol is mainly metabolized by the liver, it is a primary site of alcohol-induced adverse health effects. Alcohol intake is associated with elevated liver enzyme activities [11]. Liver enzyme dysfunction is as major predictors of mortality linked to liver disease, cardiovascular disease, diabetes and cancer [13]. In this study, we observed a significant increase of ALP in the group treated with tramadol+lager beer, followed by the gin treated groups compared to other groups, with the highest concentration seen in the normal control group as shown in Table 3. However, the activities of liver enzymes AST and ALT in alcohol beverages treated groups in our study did not approach levels that would be considered clinically abnormal [14]. Though, there was an elevated level of ALT in the tramadol and lager beer treated groups of 125.83 ± 2.41 and 126.00 ± 2.25*, respectively, compared to the normal control with a concentration of 124.50 ± 13.64 as shown in Table 3. In the presence of inflammatory conditions, there is a leakage of cytoplasmic enzymes into the circulations. Hence, ALT level will rise above that of AST. Increased level of Alkaline Phosphates (ALP) is associated with acute liver and kidney damage [15]. Results of the serum liver enzymes show that treatment with tramadol caused significant reduction in Serum AST and ALP as well as non-significant reductions in serum ALT compared to the control groups. These reductions may be due to drug-related liver toxicity [16], which is in agreement with the report of that treatment with morphine can cause a reduction in serum liver enzymes [15]. It may be an indication that the alterations in the concentration of liver enzyme within the acceptable level are not benign. Hence, further study to examine if they are link with subsequent liver disease development is highly recommended.

Note: Values are expressed as mean ± SEM, n=6; * =significantly different from group 1 at p<0.05; ^a=significantly different from Tramadol group; ^b=significantly different from Gin or Lager beer group

Table 3: Serum enzyme concentrations.

Effects on serum total bilirubin, conjugated bilirubin and Un-conjugated bilirubin (μmol/L)

Abnormal total bilirubin concentration in long-term alcohol consumption may be due to combined or isolated increases in non-conjugated and conjugated fractions. Elevated conjugated fraction signify hepatocyte damaged [17]. Hyperbilirubinemia has been positively link to alcohol consumption, with low serum concentration of unconjugated bilirubin [11]. In our observation, there was a statistically significant decrease in serum total bilirubin when in the treated groups compared to the control group. We also observed that, among the treated groups, the bilirubin level was significantly higher in the tramadol-treated group, followed by the tramadol+gin-treated group compared to the lager beer-treated group. Similar observations were seen in the conjugated and uncongested bilirubin as shown in Table 4. Our result agreed with the report of elevated total serum bilirubin concentration in Wistar rats treated with tramadol and vitamin E [18]. The elevation in serum bilirubin level may be due to the toxic effect of tramadol on the live. Howevers, a significant concentration of unconjugated bilirubin was observed in the lager beer-treated group compared to other groups. Our results agreed with the reports of [11,17] respectively.

Note: Values are expressed as mean ± SEM, n=6; * = significantly different from group 1 at p<0.05;^a= significantly different from Tramadol group.

Table 4: Serum bilirubin concentrations of the different experimental groups.

Glutathione (GSH), catalase, urea and creatinine (mg/ dL)

The increase in Reactive Oxygen Species (ROS) generation has been reported in a study conducted in Palestine on tramadol toxicity among user [15]. This could result in increased oxidative stress due to alcohol metabolism and antioxidant production by the liver [22]. The ROS react with most cellular macromolecules (DNA, protein, lipids), interfering with their physiological functions [22]. In this our study, as shown in Table 5, we observed a significant increase in the levels of GSH in all the treated groups compared to the control group, with a greater elevation observed in the tramadol+gin treated group. However, there was a significant decrease in catalase levels in the treated groups except for the gin-treated group (136.92 ± 0.41*, a) compared to the control (107.25 ± 1.32) Table 5. We also observed that, gin has a statistically significant negative effect both when treated singly or in a combined form with tramadol compared to lager-beer.

Note: Values are expressed as mean ± SEM, n=6; * =significantly different from group 1 at p<0.05; ^a=significantly different from tramadol group; ^b=significantly different from gin or lager beer group

Table 5: Serum Glutathione (GSH), Catalase, creatinine and Urea concentrations.

Elevated serum levels of creatinine and urea have been linked to tramadol and alcohol consumption with associated kidney and liver, as well as central nervous system dysfunction in sub-Saharan Africa [24]. They are key biochemical indices that are used to determine kidney function. Creatinine is used to determine glomerular filtration rate, while urea is used to determine nephrotoxic levels of xenobiotics [24]. In this study, we observed a significant increase in the levels of serum creatinine in gin and gin+tramadol treated groups compared to control, while significant decreases were observed in the tramadol, lager-beer and tramadol+lager beer treated groups compared to control (Table 5). This agreed with the report by Dic-Ijewere, et al., serum urea showed a significant increase in concomitant administration of tramadol and lager-beer compared to control group, with a significant decrease in the tramadol and lager beer-treated groups compared to the control. While there was no significant differences between the gin and the gin+tramadol-treated group compared to the control. This suggest a higher potential risk of kidney and liver damage in individual who consume more of tramadol and lager beer compared to those who depend solely on tramadol or tramadol and gin.

Effect of tramadol and alcoholic beverages on serum electrolytes (mmol/L)

Alcohol and chronic drug abuse have been observed to affect the integrity of the kidney structure and functions, as well as impairment of electrolyte level regulation in the body fluid by the kidney [25]. Renal tubular reabsorption is greatly affected by long-term alcohol intake, which in a cross-sectional study has shown a significant decrease in sodium (133.58 ± 7.8) and potassium (3.64 ± 0.64) concentrations when compared to the control (139.43 ± 3.85, sodium and 4.15 ± 0.43, potassium) [25,26]. Our results in Table 6, are in agreement with the above report as we obtained similar values of sodium and potassium concentrations when compared to control in the tramadol-treated group, gin, gin+tramadol, lager-beer+tramadol treated groups. The calcium level was significantly low (p<0.05) in the tramadol+lager-beer-treated group compared to the control. The concentrations were also low in the gin and lager-beer-treated group groups compared to the control. Our results agreed with the report of hypocalcemia and hypokalemia as common electrolyte abnormalities in observed in alcoholic-dependence patients [25,26].

Note: Values are expressed as mean ± SEM, n=6; * =significantly different from group 1 at p<0.05; ^a=significantly different from tramadol group; ^b=significantly different from gin or lager beer group

Table 6: Serum electrolytes concentrations.

As presented in Table 6 above, there was a significant increase in iron and bicarbonate (HCO₃) in concentrations of all the treated groups compared to the control groups. However, the tramadol+lager-beer-treated group was significantly high (p>0.05) in iron (492.21 ± 0.52*, a, b), followed by gin treated group (485.42 ± 1.28*, a ) compared to the control (230.55 ± 0.38) and similar results were obtained for HCO₃ with the highest concentration in the tramadol+lager-beer-treated group. This disagreed with the report of elevated serum bicarbonate levels in test subjects after tramadol and alcohol combined intake within one week of their sample collection [23]. There was a significant decrease in the chloride (Cl^-) levels in all the treated groups compared to the control, as presented in Table 6. The alteration in the levels of electrolytes may be an indication of compromised effects of alcohol and tramadol intake on renal functions [23]. The increasing incidence of alcohol and tramadol intake by young people today to enhance drunkenness is alarming, and a thing to be worried about, and this could lead to increasing cases of kidney and liver dysfunction.

Effect of alcoholic beverages and tramadol on the lipid profile (mmol/L)

The lipid profile changed, with significant decrease (p<0.05) in total cholesterol tramadol and lager beer-treated groups compared to the control group (Table 7). No significant changes were observed in the gin, tramadol+gin and tramadol+lager beer groups (Table 7). These agreed with the report of of no significant changes in tramadol-treated groups [19]. This suggests that the metabolism of lipid derangement is could be a result of cumulative effects [20]. There were also a significant increase in Triglyceride (TG) in the lager-beer and tramadol+lager beer-treated groups compared to the control and other treated group (Table 7). There were no significant changes in all the treated groups for high-density lipoprotein (HDL-c) when compared to the control group except for the tramadol+lager beer-treated group, where a significant decrease (p<0.05) was observed (Table 7). In low-density lipoprotein (LDL-c), we observed a significant increase (p>0.05) in the tramadol+lager beer-treated group compared to the control and other treated groups (Table 7).

Note: Values are expressed as mean ± SEM, n=6; * =significantly different from group 1 at p<0.05; ^a=significantly different from tramadol group; ^b=significantly different from gin or lager beer group

Table 7: Serum lipid concentrations.

Serum total cholesterol levels decreased significantly in the groups treated with tramadol (1.62 ± 0.07), lager beer (1.65 ± 0.04) and tramadol+lager beer (2.32 ± 0.05) compared to the control group (2.55 ± 0.07). There were significant increases in serum total cholesterol in the groups treated with lager beer and tramadol+lager beer compared to the group treated with only tramadol. Also, there was a significant increase in the group treated with tramadol+lager beer compared to the group treated with lager beer. However, no significant changes were observed among the gin, lager beer, tramadol and tramadol+gin-treated group compared to the control.

There are inconsistency in opium, morphine, heroin and tramadol studies in humans compared to animal studies, where it has proven to have deleterious effects on dyslipidemia and lipid profile when consumed with alcohol [20]. Increased serum triglyceride, total and LDL cholesterol and decreased HDL cholesterol have been reported [20,21].

Effect of tramadol and alcoholic beverages on haematological indices (%)

A general change in haematological parameters is an indication of disease condition [22]. In this study, there were significant decreases (p<0.05) WBC in tramadol, gin, gin+tramadol, lager-beer and tramadol+lager-beer compared to the control. This agreed with the report of [11,24] of decreased in WBC levels sin tramadol treated in their experiment. The WBC plays key role as a component of the immune system and a decrease in its level is an indication of reduced immune function as a result of tramadol and alcohol intake (Table 8).

Note: Values are expressed as mean ± SEM, n=6; * =significantly different from group 1 at p<0.05; ^a=significantly different from tramadol group; ^b=significantly different from gin or lager beer group

Table 8: Haematology parameters.

Haemoglobin (Hb), an oxygen transport metalloprotein present in the red blood cell and is found only in the RCBs. A decreases in the RBC level is directly linked to low level of haemoglobin which could directly result in hypoxic conditions in the tissues. In this, we observed a significant increase (p>0.05) in RBC in all the treated groups compared to the control. This result disagreed with the report of [24] RBC decreased in tramadol-treated group compared to the control. However, significant increases (p>0.05) were observed in gin and tramadol+gin treated-groups when compared to other treated groups. Though, the reason for the increase in in PCV, platelet, Hb and RBC in our study remain unclear, and further experiment is highly recommended.

Histopathological examination shows normal photomicrograph of hepatic tissue of Wistar rats in the normal control group (Figure 1).

Figure 1: Histology of the liver: Control group at X400-Section

The tramadol-treated group (Figure 2) shows photomicrograph of hepateocytes radiating outward from the central vein urea, indicating a degenerative change in the hepatocytes, congested of the central vein and portal urea with a moderate amount of inflammatory infiltrate, mainly lymphoscytes.

Figure 2: Histology of the liver: Tramadol treated group at X400-Section

Centrotubular vacuolation was seen in (Figure 3 and Figure 4) treated with gin and lager beer, respectively. While tramadol+lager beer and tramadol+gin-treated groups, showed an increases in hepatic degenerative effects with observable cytolysis as compared to the control group (Figure 5 and Figure 6), respectively. These results are in agreement with several studies on albino rats of reported acute and long-term treatment with morphine linked to hepatoxic effects during metabolism, such as cytolysis, necrosis and haemorrhage [26]. Noteworthy is that a concomitant intake of alcohol and tramadol is highly deleterious for both gin and lager beer.

Figure 3: Histology of the liver: Gin-Liver, Centrolobular area at X400-Section

Figure 4: Histology of the liver: Lager beer-liver centrilobular area X400

Figure 5: Histology of the liver: Tramadol+gin-Liver, Centrolobular area X400-Section.

Figure 6: Histology of the liver: Group 4 (tramadol+lager beer) liver, centrolobular area X400-Section.

A photomicrograph of the renal cortex of Wistar rats in the control group (Figure 7) shows prominent glomeruli and renal tubeless within the renal parenchyma. The glomeruli are evenly distributed with the cortical area and consist of a cellular matrix and a widely open bowman capsule.

Figure 7: Histology of the kidney: Control kidney X400-section of glomeruli and renal tubules

The tramadol-treated group (Figure 8) showed glomeruli are atrophic with a cellular mesangium and narrowed bowman space. The renal tubules are lined by cuboidal to columnar epithelial cells with their luminal cavity mostly empty and few containing secretion. The interstitium was compacted, and the blood vessels were congested, indicating mild glomerular injury. This injury may be due to the effect of tramadol as it passes through the glomerular tubule (Figure 9).

Figure 8: Histology of the kidney: Tramadol-kidney X400-Section cortical of the glomeruli and renal tubules.

Figure 9: Histology of the kidney: Gin kidney,cortical area x400-section of the glomeruli and renal tubules within the renal parenchyma.

The group treated with lager beer shows glomeruli and renal tubules within the renal parenchyma. The glomeruli are evenly distributed and consist of a narrowed bowman space with a cellular mesangium consisting of proliferating mesangial cells and congested arterioles. The glomeruli were swallowed. The renal tubules were lined by swollen cuboidal to columnar epithelial cells with their luminal cavity empty. The interstitium was compact and contained thick wall blood vessels. This suggested necrotic effect of the lager-beer on the blood vessels within the kidney (Figure 10).

Figure 10: Histology of the kidney: Lager-beer kidney,cortical area x400-section of the glomeruli and renal tubules within the renal parenchyma.

Also, the group treated with tramadol+lager beer showed irregularly shaped glomeruli and renal tubules within the renal parenchyma. The glomeruli were evenly distributed and consisted of a narrower bowman space with a hypercellular mesangium and congested arterioles (Figure 11).

Figure 11: Histology of the kidney: Tramadol+gin-Kidney cortical area x400-section of the glomeruli and renal tubules within the renal parenchyma.

The renal tubeless lined by swollen cuboidal to columnar epithelia cells with collapsed luminal cavities (Figure 12). The interstitium was also compact with congested blood vessels. Similar effects were also observed in Figure 3 and Figure 5 treated with gin and a concomitant of tramadol+gin. Our results are in agreement [27,28], who reported necrosis, vacuolization of renal tubule cell infiltration, as well as increased urea and creatinine levels in rats. Deductively, this could be a result of the toxicokinetics effects of gin, lager beer and tramadol since a good percentage of the drug (30%) is eliminated via the kidney. Therefore, there are possibilities of cellular damage as drugs are excreted through the kidney resulting in renal dysfunction [29,30].

Figure 12: Histology of the kidney: Tramadol+lager beer-Kidney cortical area x400-section of the glomeruli and renal tubules within the renal parenchyma.

Conclusion

The data obtained in this study, showed that tramadol intake concomitant with gin, lager beer have deleterious effects on our health. It showed retarded growth, alteration of liver enzymes concentration, which is an indication of liver damage. 

The electrolytes, urea, and creatinine changes are clear indication of the negative effects of tramadol and alcohol on the kidney functions. The study also revealed compromised immune system as the concomitant intake of alcohol and tramadol significantly lower blood level of WBC known to be key player in body defense against infection. 

Tramadol intake concomitant with gin or lager beer, cause liver and kidney injury thereby, affecting the integrity and function of these vital organs. However, we observed that, a concomitant intake of tramadol and lager beer is more harmful to the Wistar rats compare to groups treated with gin, tramadol, and tramadol+gin. Hence, the need for proper sensitization and education of the masses of the implication of concomitant drug and alcohol abuse among young people.

Funding

This study did not received any external funding.

Competing Interest

Victor Samson EKAM, Echu Francis OBUN, Igbang Jerome OKPUTU and Kevin Douglas ABANG are academic researchers and hereby, declare no conflict of interest.

Ethical Approval

This study was approved by the institution Ethics committee for the handling of human and animal subjects of the college of Faculty of Basic medical Sciences of the University of Calabar, Calabar Nigeria. All the standard ethics were strictly followed in this research.

Authors’ Contributions

Ekam V. S-participated in the design, interpretation of data and overall review of the manuscript; Obun F. E-carried out sample collection, animal study, participated in the laboratory analysis; Okputu J. I-participated in data analysis, drafting the manuscript, revising the manuscript and the approval of the final version; and Abang D. K-in the administration of alcohol and drug the rats, sample collection, data analysis and drafting of the manuscript.

Acknowledgement

The authors acknowledge the research support of Mr Collins in the laboratory and the leadership of Biochemistry Department, University of Calabar, for making this research possible by providing the enabling environment.

References

1. B. Joana, F. Juliana, G. Fernanda, L. Sandra, A. Luís, et al. Repeated administration of clinical doses of tramadol and tapentadol causes hepato- and nephrotoxic effects in Wistar rats, Pharmaceuticals, 13(2020): 149.
2. A. K. Hussein, M. H. Hellal, M. M. Farag, S. Sherein, A. E. Ibtesam, et al. Effects of acute sub-lethal dose of tramadol on α-2-adrenergic receptors and liver histopathology in rat, Glob J Curr Res, 1(2013): 2320-2920.
3. S. Chen, C. Argaez. Tramadol for the management of pain in adult patients: a review of clinical effectiveness—an update, CADTH, 1(2018): NBK538277.
4. I. A. Amany, E. Khalifa, M. Medhat, H. A. Fawzy, H. N. Abdallah, et al. Retrospective review of tramadol abuse, Slov Vet Res, 55(2018): 471–483.
5. U. M. Ann, K. Axel. Tramadol as a pain relieving and physical work performance enhancement medication, Drugs Alcohol Today, 1(2019): 1–5.
6. D. Mavis, A. Francis. Factors associated with tramadol abuse: a cross‑sectional study among commercial drivers and assistants in the Accra metropolitan area of Ghana, Drugs Real World Outcomes, 8(2021): 337–347.
7. National Institute on Alcohol Abuse and Alcoholism. Medication for the treatment of alcohol use disorder: a brief guide, SAMHSA, (2015): 15-4907.
8. J. Porazka, E. Szatek, W. Pojda, M. Czerwinski, T. Goraus, et al. Influence of obesity and type 2 diabetes mellitus on the pharmacokinetics of tramadol after oral dose administration, Eur J Drug Metab Pharmacokinet, 44(2019): 579–584.
9. C. A. Kase, A. D. Peira, K. E. Schaumberg. The relationship of alcohol use to weight loss in the context of behavioral weight loss treatment, Appetite, 99(2016): 105–111.
10. B. Usharani, R. Vennila, N. Nalini. Biochemical changes in alcohol—a case study, Int J Res Pharm Biomed Sci, 3(2012): 201–205.
11. A. Walter, M. Asshraf. A study correlating the quantity and duration of alcohol consumption with liver function tests, IOSR J Dent Med Sci, 13(2019): 70–75.
12. A. Sanjiv, V. L. Fulgoni, R. L. Harris. Assessing alcohol intake and its dose-dependent effects on liver enzymes by 24h recall and questionnaire using NHANES 2001–2010 data, Nutr J, 15(2016): 62.
13. S. K. Kunutsor, T. A. Apekey, D. Seddoh, J. Walley. Liver enzymes and risk of all-cause mortality in general populations: a systematic review and meta-analysis, Int J Epidemiol, 43(2014): 187–201.
14. Mayo Clinic. Liver function tests procedures, Mayo Clin Proc, (2012): PRC-20012602.
15. A. E. Abdelraouf, E. S. Noor, T. Abu, N. E. Hend, M. H. Ikram. Tramadol-induced liver and kidney toxicity among abusers in Gaza Strip, Palestine, Jordan J Biol Sci, 8(2015): 133–137.
16. S. Carissa. Low creatinine: what you need to know, Self-Decode, 16(2018): 2–5.
17. O. Elanchezhian, T. Yoganandh, S. Mayilsamy, R. Shankar. Comparison of haematological parameters between alcoholics and non-alcoholics, Int J Res Med Sci, 5(2017): 5041–5047.
18. O. Obembe, T. O. Latoke. Reproductive and biochemical parameters of tramadol and vitamin E in acutely treated male Wistar rats, Afr J Med Med Res, 48(2019): 243–249.
19. J. Barbosa, J. Faria, F. Garcez, S. Leal, L. Afonso, et al. Repeated administration of clinical doses of tramadol and tapentadol causes hepato- and nephrotoxic effects in Wistar rats, Pharmaceuticals Basel, 13(2020): 149–157.
20. H. Najafipour, A. Beik. The impact of opium consumption on blood glucose level, serum lipids and blood pressure, and related mechanisms, Front Physiol, 7(2016): 138.
21. A. B. Nair, S. Jacob. A simple practice guide for dose conversion between animals and human, J Basic Clin Pharm, 7(2016): 27–31.
22. S. Liz, M. Flavia, P. E. Martins. Alcohol-associated tissue injury: current views on pathophysiological mechanisms, Annu Rev Physiol, 84(2022): 87–112.
23. E. O. Dic-Ijiewere, B. O. Humphrey. CYP24A1 and CYP3A4 levels, renal and hepatic changes, and incidence of oxidative stress in tramadol-alcohol concomitant misuse, Cureus, 15(2023): e36877.
24. A. Owoade, A. Adewale, S. O. Olubukola, et al. Haematological and biochemical changes in blood, liver and kidney tissues under the effect of tramadol treatment, J Alcohol Drug Depend, 7(2019): 1000326.
25. P. Chandini, J. Mathai. Serum electrolyte levels in patients with alcohol dependence syndrome, Int J Contemp Med Res, 4(2015): 77–83.
26. M. Raut, S. Ghimire, P. Regmi, S. K. Raut, B. Jha. Level of electrolytes in chronic alcoholic patients, Ann Clin Chem Lab Med, 1(2015): 31–34.
27. Z. Z. Muslim. The biochemical and histological effects of tramadol on liver and kidney of albino mice, Thi-Qar Med J, 15(2018): 1–4.
28. S. Atici, L. Cinel, L. Cine, N. Doruk, G. Eskandari, et al. Liver and kidney toxicity in chronic use of opioids: an experimental long-term treatment model, J Biosci, 30(2015): 245–252.
29. N. Eizadi-Mood, D. Ozcan, M. Hedaiaty, A. M. Sazghabaee, P. H. Mirmoghtadaee. Does naloxone prevent seizure in tramadol intoxicated patients?, Int J Prev Med, 5(2014): 302–307.
30. J. I. Okputu, C. O. Ironya, M. Obi-Abang, E. G. Egbung. Nephroprotective potential of Persea americana (avocado) ethanol-water seed extract and glucovance in streptozotocin-induced Wistar rats, Trop J Nat Prod Res, 6(2022): 244–255.

Copyright: © 2025 Victor Samson Ekam, 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 work is properly cited..