The Hepatotoxic Effect of Sildenafil Citrate and Its Combination with Tramadol on Male Wistar Rats is Ameliorated with Vitamin E Supplementation

Main Article Content

J. N. Nwangwa
A. L. Udefa
P. M. Obi
C. E. Obeten
S. Okpa

Abstract

Aims: This study investigated the effect of vitamin E on serum liver enzymes and bilirubin concentrations in male Wistar rats treated with sildenafil citrate (SC) and a combination of SC and tramadol on the background that these drugs cause oxidative damage to the liver.

Methods: Thirty male Wistar rats (180-200 g) were randomly divided into six groups (n=5) thus: control (0.2 ml vehicle – olive oil), SC-treated group (Sil) (10 mg/kg of SC), SC+tramadol-treated group (Sil+Tra) (10 mg/kg of SC and 20 mg/kg of tramadol), vitamin E-treated group (Vit E) (100mg/kg of vitamin E), SC+vitamin E-treated group (Sil+Vit E) (received SC and vitamin E) and SC+tramadol+vitamin E-treated group (Sil+Tra+Vit E) (received SC, tramadol and vitamin E). Drugs were administered orally once daily for four weeks after which blood samples were obtained and used to measure serum concentrations of liver enzymes (AST, ALT and ALP) and bilirubin.

Results: Serum AST, ALT, ALP, total bilirubin (TB) and unconjugated bilirubin (UCB) concentrations were significantly (p<0.001) increased in Sil and Sil+Tra compared with control and Vit E and significantly (p<0.01) decreased in Sil+Vit E and Sil+Tra+Vit E compared with Sil and Sil+Tra. Serum conjugated bilirubin (CB) concentration and percentage conjugation of bilirubin significantly decreased (p<0.001) in Sil and Sil+Tra compared with control and Vit E and increased (p<0.01) in Sil+Vit E and Sil+Tra+Vit E compared with Sil and Sil+Tra.

Conclusion: SC, administered separately and in combination with tramadol altered liver function. However, vitamin E supplementation was able to ameliorate this alteration in liver function.

Keywords:
Bilirubin, liver enzymes, sildenafil citrate, tramadol, vitamin E, Wistar rats

Article Details

How to Cite
Nwangwa, J., Udefa, A. L., Obi, P. M., Obeten, C. E., & Okpa, S. (2019). The Hepatotoxic Effect of Sildenafil Citrate and Its Combination with Tramadol on Male Wistar Rats is Ameliorated with Vitamin E Supplementation. Archives of Current Research International, 18(1), 1-10. https://doi.org/10.9734/acri/2019/v18i130123
Section
Original Research Article

References

Abdel-Hamid IA, Andersson KE, Waldinger MD, Anis TH. Tramadol abuse and sexual function. Sexual Medicine Reviews. 2016;4(3):235-246.

Nna VU, Akpan UP, Okon VE, Atangwho IE. Hepatotoxicity following separate administration of two phosphodiesterase-5 inhibitors (sildenafil & tadalafil) and opioid (tramadol); evaluation of possible reversal following their withdrawal. J App Pharm Sci. 2015;5(8):105-113.

Oka VO, Udefa AL, Nna VU, Owu DU. Sildenafil citrate and tramadol administered separately and in combination affects basal metabolic rate, triiodothyronine (T3) and cortisol levels in albino wistar rats. Trends in Medical Research. 2015;10(3):51-62.

Bechara A, Casabé A, De Bonis W, Helien A, Bertolino MV. Recreational use of phosphodiesterase type 5 inhibitors by healthy young men. The Journal of Sexual Medicine. 2010;7:3736-3742.

Nna VU, Ani EJ, Ofutet EO, Ofem OE, Iroh CE, Osim EE. Recurrent side effects following chronic recreational use of sexual stimulants among male subjects in Calabar, Cross River State, Nigeria. Der Pharmacia Lettre. 2014;6(6):56-61.

Nna VU, Udefa AL, Ofutet EO, Osim EE. Testicular and epididymal histology of rats chronically administered high doses of PDE5 inhibitors and tramadol. Nigerian Journal of Physiological Sciences. 2017;32:55-61.

Eweka AO, Eweka A. The effects of sildenafil citrate on the liver and kidneys of adult Wistar rats (Rattus norvegicus) – A histological study. Sexual Dysfunctions - Special Issues; 2011.
Available:http://www.intechopen.com/books/sexual-dysfunctions-special-issues/the-effects-of-sildenafil-citrate-on-theliver-and-kidneys-of-adult-wistar-rats-rattus-norvegicus-a

Atici S, Cinel I, Cinel L, Doruk N, Eskandari G, Oral V. Liver and kidney toxicity in chronic use of opioids: an experimental long term treatment model. J Biosci. 2005;2:245-252.

Sheweita SA, Almasmari AA, El-Banna SG. Tramadol-induced hepato- and nephrotoxicity in rats: Role of curcumin and gallic acid as antioxidants. PLoS ONE. 2018;13(8):e0202110. Available:https://doi.org/10.1371/journal.pone.0202110

Baunthiyal M, Singh V, Dwivedi S. Insights of antioxidants as molecules for drug discovery. International Journal of Pharmacology. 2017;13(7):874-889.

Pizzino G, Irrera N, Cucinotta M, Pallio G, Mannino F, Arcoraci V, et al. Oxidative stress: Harms and benefits for human health. Oxidative Medicine and Cellular Longevity; 2017.
DOI: org/10.1155/2017/8416763

El Hadi H, Vettor, Rossato M. Vitamin E as a treatment for nonalcoholic fatty liver disease: Reality or myth? Antioxidants (Basel). 2018;7(1):12.
DOI: 10.3390/antiox7010012

Maheswari E, Saraswathy GR, Santhranii T. Influence of Vitamin E on hepatotoxicity and oxidative stress. International Journal of Research in Pharmacy and Biosciences. 2015;2(3):30-38.

Pacana T, Sanyal AJ. Vitamin E and non-alcoholic fatty liver disease. Curr Opin Clin Nutr Metab Care. 2012;15(6):641-648.
DOI: 10.1097/MCO.0b013e328357f747

Nwangwa JN, Udefa AL, Obeten CE, Obi PM, Adie PU, Kanu UJ. Vitamin E supplementation counters the hepatotoxic effects of tramadol on male Wistar rats. IOSR Journal of Dental and Medical Sciences. 2019;18(6).

Helsinki. World Medical Association Declaration of Helsinki. Adopted by the 18th WMA General Assembly, Helsinki, Finland; 1964.

Reitman S, Frankel S. Determination of aminotransaminases in serum. American Journal of Clinical Pathology. 1957;28:50-56.

King EJ, Armstrong AR. Canadian Medical Association. Journal. 1964;31:376.

Sherlock S, Lunec J. Free radical and antioxidant system in health and disease. British Journal of Hospital Medicine. 1951;43:334-344

Aragon G, Younossi ZM. When and how to evaluate mildly elevated liver enzymes in apparently healthy patients. Cleveland Clinic Journal of Medicine. 2010;77(3):195-204.

Ashwood ER. Tietz textbook of clinical chemistry. 2nd ed. Philadelphia USA: WB Saunders Co.; 1994.

Kendall MJ, Cockel R, Becker J, Hawkins CF. Raised serum alkaline phosphatase in rheumatoid Disease: An index of liver dysfunction? Ann. Rheum. 1970;29:537-540.

Rukhshanda S, Razia I, Muhammad NA, Anum Z, Javed I, Muhammad SA. Effects of tramadol on histopathological and biochemical parameters in mice (Mus musculus) model. Global J Pharmacol. 2014;114-19.

Volpe JJ. Bilirubin and Brain Injury, in Neurology of the Newborn. 2003;521-546.

Elmanama AA, Abu Tayyem NES, Essawaf HN, Hmaid IM. Tramadol-Induced liver and kidney toxicity among abusers in Gaza Strip, Palestine. Jordan Journal of Biological Sciences. 2015;8(2):133-137.

Sgro M, Campbell D, Shah V. Incidence and causes of severe neonatal hyperbilirubinemia in Canada. Canadian Medical Association Journal. 2006;175(6):587-590.