HEPATOPROTECTIVE EFFECT OF ZINC COMPLEX OF BETULINIC ACID ON PYRAZINAMIDE INDUCED HEPATOTOXICITY IN MICE

Authors

  • Alia Rehman Mohtarma Benazir Bhutto Shaheed Medical College Mirpur, Azad Kashmir
  • Adnan Jehangir Punch Medical College Rawalakot, AJK, Pakistan
  • Fatima Mohammadi International Islamic Medical College, Rawalpindi, Pakistan
  • Salma Salim Mohi-ud-din Islamic Medical College, Mirpur AJK, Pakistan
  • Rabia Iftikhar International Islamic Medical College, Rawalpindi, Pakistan
  • Amber Rashid International Islamic Medical College, Rawalpindi, Pakistan

DOI:

https://doi.org/10.69656/pjp.v19i3.1389

Keywords:

hepatotoxicity, Betulinic acid, pyrazinamide, ALT, bilirubin, Hepatoprotection

Abstract

Background: Hepatotoxicity is a common side effect of pyrazinamide, a first line anti-tuberculous drug. Objective of this study was to determine the hepatoprotective effect of zinc complex of Betulinic acid (BA) on pyrazinamide induced hepatotoxicity in mice. Methods: This experimental, randomized control study was conducted at Islamic International Medical College, Rawalpindi, and National Institute of Health Islamabad from 1 Sep 2020 to 31 Aug 2021. Thirty male Balb/c albino mice were divided into three groups each having 10 mice. Group 1 received normal diet with no medication. Group 2 (NC) received pyrazinamide 500 mg/Kg daily for 28 days. Group 3 (DC) received Zinc complex of Betulinic acid 1 mg/Kg/day per oral once daily along with pyrazinamide. Final sampling was done on day 28 by intracardiac puncture for estimation of serum ALT and bilirubin level. Data was analysed on SPSS-21. Comparisons between the groups were analyzed using one way ANOVA (Post Hoc Tuckey test), and p<0.05 was considered significant. Results: Zinc complex of Betulinic acid treated group had significantly decreased serum ALT (58.00±5.639) and bilirubin (0.617±0.601) in comparison with pyrazinamide treated group. Conclusion: Zinc complex of Betulinic acid exerted significant hepatoprotective activity in pyrazinamide induced hepatotoxicity.

Pak J Physiol 2023;19(3):36–8

Downloads

Download data is not yet available.

References

Shehata AA, Farrag AA, Elhady EE, Elsheikh HH. Effect of Mushroom Fungus Feeding on Induced Hepatotoxicity Rats. Egypt J Appl Sci 2020;35(11):127–42.

Thuwaini MM, Al-Derawi KH, Kadhem H. The possible protective effect of carthmustinctorius (Leaves) on anti-tuberculosis (rifampin & isoniazid) drugs-induced hepatotoxicity in rats. Int J Pharm Res 2018;10(4):516–22.

Khan MD, Ahmad B, Hussain A, Ishaq T, Haider O, Murtaza HG. Frequency of drug-resistant mycobacterium tuberculosis in Chiniot, Pakistan. Life Sci J Pak 2021;3(1):3–7.

Abebe G, Bonsa Z, Kebede W. Treatment outcomes and associated factors in tuberculosis patients at Jimma University Medical Center: A 5 Year retrospective study. Int J Mycobacteriol 2017;6(3):239–45.

Marjani M, Fahimi F, Sadr M, Dizaji MK, Moniri A, Khabiri S, et al. Evaluation of Silymarin for management of anti-tuberculosis drug induced liver injury: A randomized clinical trial. Gastroenterol Hepatol Bed Bench 2019;12(2):138–42.

Hussain Z, Zhu J, Ma X. Metabolism and hepatotoxicity of Pyrazinamide, an antituberculosis drug. Drug Metab Dispos 2021;49(8):679–82.

Zhang Y, Guo H, Hassan HM, Ding PP, Su Y, Song Y, et al. Pyrazinamide induced hepatic injury in rats through inhibiting the PPAR? pathway. J Appl Toxicol 2016;36(12):1579–90.

Ríos JL, Máñez S. New pharmacological opportunities for betulinic acid. Planta Med 2018;84(1):8–19.

Silva FSG, Oliveira PJ, Duarte MF. Oleanolic, ursolic and betulinic acids as food supplements or pharmaceutical agents for type 2 diabetes: promise or illusion? J Agric Food Chem 2016;64(15):2991–3008.

Yi J, Xia W, Wu J, Yuan L, Wu J, Tu D, et al. Betulinic acid prevents alcohol-induced liver damage by improving the antioxidant system in mice. J Vet Sci 2014;15(1):141–8.

Marreiro DD, Cruz KJ, Morais JB, Beserra JB, Severo JS, de Oliveira AR. Zinc and oxidative stress: Current mechanisms. Antioxidants (Basel) 2017;6(2):24.

Aftab K. Hepatoprotective role of zinc sulphate in carbon tetrachloride induced liver toxicity. J Pharmacol Clin Res 2016;1(3):1–4.

Liu J, Zhou ZX, Zhang W, Bell MW, Waalkes MP. Changes in hepatic gene expression in response to hepatoprotective levels of zinc. Liver Int 2009;29(8):1222–9.

Jarosz M, Olbert M, Wyszogrodzka G, M?yniec K, Librowski T. Antioxidant and anti-inflammatory effects of zinc. Zinc-dependent NF-?B signaling. Inflammopharmacology 2017;25(1):11–24.

Taziki S, Khori V, Jahanshahi M, Seifi A, Babakordi F, Nikmahzar E. Protective role of taurine against hepatotoxicity induced by pyrazinamide in rats. Natl J Physiol Pharm Pharmacol 2018;8(6):824–8.

Zheng ZW, Song SZ, Wu YL, Lian LH, Wan Y, Nan JX. Betulinic acid prevention of D-galactosamine/lipopolysaccharide liver toxicity is triggered by activation of Bcl-2 and antioxidant mechanisms. J Pharm Pharmacol 2011;63(4):572–8.

Abdullah, Khan MA, Ahmad W, Adhikari A, Ibrar M, Rehman MU, et al. Exploration of hepatoprotective potential and phytochemicals of ziziphus oxyphylla edgew. Pak Vet J 2020;40(4):431–6.

Al-Jawad FH, Sharquie KE, Abu Raghif, Nashtar SB. Hepatoprotective effects of zinc sulphate and silymarin against thallium-induced poisoning in rats. Iraqi Acad Sci J 2016;1:42–57.

Siddique W, Rashid N, Warraich NY, Talat H, Talha MU, Siddique H, et al. Comparison of hepatoprotective effect of silymarin and zinc sulfate against hepatotoxicity induced by isoniazid and rifampicin in albino rats. Pakistan J Med Heal Sci 2020;14(1):113–9.

Downloads

Published

30-09-2023

How to Cite

1.
Rehman A, Jehangir A, Mohammadi F, Salim S, Iftikhar R, Rashid A. HEPATOPROTECTIVE EFFECT OF ZINC COMPLEX OF BETULINIC ACID ON PYRAZINAMIDE INDUCED HEPATOTOXICITY IN MICE. Pak J Phsyiol [Internet]. 2023 Sep. 30 [cited 2024 Nov. 23];19(3):36-8. Available from: https://pjp.pps.org.pk/index.php/PJP/article/view/1389