Can Sildenafil Citrate Be a Game Changer in the Management of Tuberculosis? A Food for Thought?

Najma  Hameed; Khalid  Farooq

doi:10.54112/bcsrj.v6i5.1762

Authors

Najma Hameed Department of Anatomy, Khyber Girls Medical College Peshawar, Pakistan
Khalid Farooq Department of Urology, Lady Reading Hospital Peshawar, Pakistan

DOI:

https://doi.org/10.54112/bcsrj.v6i5.1762

Keywords:

Hepatotoxicity; INH-RIF; oxidative stress; sildenafil citrate; Biochemical changes

Abstract

Isoniazid (INH) and Rifampicin (RIF) are cornerstone drugs in tuberculosis therapy but are known to cause hepatotoxicity. Sildenafil citrate, a phosphodiesterase-5 inhibitor, has shown potential antioxidant and anti-inflammatory properties, yet its hepatoprotective effects have not been extensively evaluated. Objective: To investigate the biochemical changes induced by combined INH-RIF therapy and assess the potential hepatoprotective effects of sildenafil treatment in a murine model. Methods: This randomized experimental study involved 21 Swiss albino mice (25–35 g), divided into three groups (n=7 each) using simple balloting. Group C (control) received 0.4 mL/kg normal saline intraperitoneally for 21 days. Group R (INH-RIF) was administered isoniazid and rifampicin (50 mg/kg each) intraperitoneally, daily for 21 days. Group S (INH-RIF + Sildenafil) received the same INH-RIF regimen with concurrent oral sildenafil (10 mg/kg) via gastric gavage. At the end of treatment, serum liver function tests (LFTs) were analyzed. Data were processed using descriptive statistics; inter-group differences were assessed using appropriate statistical tests with significance set at p < 0.05. Results: Group R exhibited significant elevation in serum hepatic enzymes indicating hepatotoxicity. Group S showed marked improvement in LFT parameters compared to Group R, suggesting attenuation of hepatotoxicity. Group C maintained normal hepatic profiles. Sildenafil administration resulted in a statistically significant reduction in biochemical markers of liver injury. Conclusion: Sildenafil citrate demonstrates a protective role against INH-RIF-induced hepatotoxicity, supporting its potential therapeutic use in minimizing anti-tuberculous drug-induced liver injury.

Downloads

Download data is not yet available.

References

Laghari M, Sulaiman SA, Khan AH, Memon N. Epidemiology of tuberculosis and treatment outcomes among children in Pakistan: a 5-year retrospective study. PeerJ. 2018 Jul 27; 6:e5253.

D'Ambrosio L, Dara M, Tadolini M, Centis R, Sotgiu G, Van Der Werf MJ, Gaga M, Cirillo D, Spanevello A, Raviglione M, Blasi F. Tuberculosis elimination: theory and practice in Europe. European Respiratory Journal. 2014 May 1; 43(5):1410-20.

Pan Y, Cao M, You D, Qin G, Liu Z. Research progress on the animal models of drug-induced liver injury: current status and further perspectives. BioMed Research International. 2019 Apr 15; 2019.

Humayun F, Tahir M, Lone KP. HISTOLOGICAL EFFECTS OF ISONIAZID ON THE LIVER OF ALBINO MICE. Khyber Medical University Journal. 2017 Apr 1; 9(2).

Schaberg T, Rebhan K, Lode H. Risk factors for side-effects of isoniazid, rifampin and pyrazinamide in patients hospitalized for pulmonary tuberculosis. European Respiratory Journal. 1996 Oct 1; 9(10):2026-30.

Ramappa V, Aithal GP. Hepatotoxicity related to anti-tuberculosis drugs: mechanisms and management. Journal of clinical and experimental hepatology. 2013 Mar 1; 3(1):37-49.

Čustović S, Muzika V, Mornjaković Z, Ćosović E, Kapić D. Qualitative histological study of isoniazid-rifampicin induced liver injury in rats. Folia Medica Facultatis Medicinae Universitatis Saraeviensis. 2015 Dec 31; 50(2).

Sodhi CP, Rana SV, Mehta SK, Vaiphei K, Attari S, Mehta S. Study of oxidative stress in isoniazid-rifampicin induced hepatic injury in young rats. Drug and chemical toxicology. 1997 Jan 1; 20(3):255-69.

Bigoniya P, Singh CS, Shukla A. A comprehensive review of different liver toxicants used in experimental pharmacology. International Journal of Pharmaceutical Sciences and Drug Research. 2009 Oct;1(3):124-35.

Hatzimouratidis K. Sildenafil in the treatment of erectile dysfunction: an overview of the clinical evidence. Clinical interventions in aging. 2006 Dec;1(4):403.

Sheweita S, Salama B, Hassan M. Erectile dysfunction drugs and oxidative stress in the liver of male rats. Toxicology reports. 2015 Jan 1;2:933-8.

Said E, Said SA, Gameil NM, Ammar EM. Modulation of thioacetamide-induced liver fibrosis/cirrhosis by sildenafil treatment. Canadian journal of physiology and pharmacology. 2013;91(12):1055-63.

Ekor M, Odewabi AO, Kale OE, Bamidele TO, Adesanoye OA, Farombi EO. Modulation of paracetamol-induced hepatotoxicity by phosphodiesterase isozyme inhibition in rats: a preliminary study. Journal of basic and clinical physiology and pharmacology. 2013 Feb 1;24(1):73-9.

Rizk AA, Shawky YM, Motawie AG. Can sildenafil citrate ameliorate cisplatin-induced nephrotoxicity? Crosstalk between the possible mechanisms. Eur. j. anat. 2019;23(2):113-9.

Vitaglione P, Morisco F, Caporaso N, Fogliano V. Dietary antioxidant compounds and liver health. Critical reviews in food science and nutrition. 2005 Feb 10;44(7-8):575-86.

Alía M, Horcajo C, Bravo L, Goya L. Effect of grape antioxidant dietary fiber on the total antioxidant capacity and the activity of liver antioxidant enzymes in rats. Nutrition Research. 2003 Sep 1;23(9):1251-67.

Pal R, Vaiphei K, Arbab Sikander KS, Rana SV. Effect of garlic on isoniazid and rifampicin-induced hepatic injury in rats. World Journal of Gastroenterology: WJG. 2006 Jan 28;12(4):636.

Pal R, Rana S, Vaiphei K, Singh K. Effect of different doses of carotenoids in isoniazid-rifampicin induced hepatotoxicity in rats. Tropical Gastroenterology. 2010 Jul 23;29(3).

Jatav SK, Kulshrestha A, Zacharia A, Singh N, Tejovathi G, Bisen PS, Prasad GB. Spirulina maxima protects the liver from Isonazid and Rifampicin drug toxicity. Journal of evidence-based complementary & alternative medicine. 2014 Jul;19(3):189-94.

Lian Y, Zhao J, Xu P, Wang Y, Zhao J, Jia L, Fu Z, Jing L, Liu G, Peng S. Protective effects of metallothionein on isoniazid and rifampicin-induced hepatotoxicity in mice. PLOS ONE. 2013 Aug 13;8(8):e72058.

Yang Y, Jiang L, Wang S, Zeng T, Xie K. Diallyl trisulfide protects the liver against

hepatotoxicity induced by isoniazid and rifampin in mice by reducing oxidative stress

and activating Kupffer cells. Toxicology research. 2016 May 1;5(3):954-62.

Li S, Tan HY, Wang N, Zhang ZJ, Lao L, Wong CW, Feng Y. The role of oxidative stress and antioxidants in liver diseases. International journal of molecular sciences. 2015 Nov;16(11):26087-124.

Adhvaryu MR, Reddy NM, Vakharia BC. Prevention of hepatotoxicity due to anti tuberculosis treatment: a novel integrative approach. World journal of gastroenterology: WJG. 2008 Aug 14;14(30):4753.

24Tetsi L, Charles AL, Georg I, Goupilleau F, Lejay A, Talha S, Maumy-Bertrand M, Lugnier C, Geny B. Effect of the phosphodiesterase 5 inhibitor sildenafil on ischemia-reperfusion-induced muscle mitochondrial dysfunction and oxidative stress. Antioxidants. 2019 Apr;8(4):93.