Hepatoprotective Effects of Silymarin and Walnut Leaf Extract in Isoniazid and Rifampicin   Induced Hepatotoxicity

Authors

  • Dr.Maleeha Abbas Department of Pharmacology, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad Pakistan
  • Moosa Khan Department of Pharmacology, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad Pakistan
  • Adeel Abbas Raja Department of Pharmacology, Azad Jammu Kashmir Medical College, Muzaffarabad, Azad Jammu & Kashmir, Pakistan
  • Iqra Siddique Department of Pharmacology, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad Pakistan
  • Faiza Rehman Department of Pharmacology, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad Pakistan
  • Syed Muzaffar Ali Department of Pharmacology, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad Pakistan

DOI:

https://doi.org/10.51253/pafmj.v76i1.12233

Keywords:

Drug-Induced Liver Injury, Isoniazid, Rifampicin, Silymarin, Tuberculosis

Abstract

Objective: To evaluate the hepatoprotective effects of Silymarin and walnut leaf extract in isoniazid-rifampicin induced hepatotoxicity in Sprague-Dawley rats.

Study Design: Laboratory-based experimental study.

Place and Duration of Study: Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad Pakistan, from Jun to Jul 2023.

Methodology: A total of 50 rats were divided in 5 groups containing 10 rats each. Group-A was control group, in Group-B hepatotoxicity was induced by isoniazid 50mg/kg/day and Rifampicin 100 mg/kg/day co-administration daily for 14 days, Group-C was given isoniazid 50mg/kg/day and rifampicin 100 mg/kg/day and 200 mg/kg/day silymarin for 14 days , Group-D was given isoniazid 50mg/kg/day and rifampicin 100 mg/kg/and walnut leaf extract was administered at a dosage of 0.2 g/kg one hour before isoniazid, Group-E was given isoniazid 50mg/kg/day and rifampicin 100 mg/kg/day, silymarin  200 mg/kg/day and walnut leaf extract 0.2 g/kg orally for 14 days. On day fifteen, terminal blood sampling was done for estimation of serum Aspartate aminotransferase (AST), alanine amino transferase (ALT), and alkaline phosphatase (ALP).

Results: Isoniazid and Rifampicin produced severe hepatotoxicity, depicted by raised mean serum AST (168.20±4.85), ALT (233.60±29.98) and ALP (288.30±19.51). Mean AST (53.30±7.32), ALT (51.80±7.21) and ALP (133.70±7.42) levels were significantly decreased in Group-E, followed by groups C and D.

Conclusion: The combination of silymarin and walnut leaf extract is more effective in preventing liver damage as compared to their separate effects.

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References

1. Sharma D, Sarkar D. Pathophysiology of tuberculosis: An update review. Pharma Tutor 2018; 6(2): 15-21.

https://dx.doi.org/10.29161/PT.v6.i2.2018.15

2. Lyon S, Rossman M. Pulmonary Tuberculosis. Microbiol Spectr 2017; 5(1): 5-128.

https://doi.org/10.1128/microbiolspec.tnmi7-0032-2016

3. Su Q, Kuang W, Hao W, Liang J, Wu L, Tang C, et al. Antituberculosis Drugs (Rifampicin and Isoniazid) Induce Liver Injury by Regulating NLRP3 Inflammasomes. Mediators Inflamm 2021; 2021(1): 8086253.

https://doi.org/10.1155/2021/8086253

4. Sanjay S, Girish C, Toi PC, Bobby Z. Gallic acid attenuates isoniazid and rifampicin-induced liver injury by improving hepatic redox homeostasis through influence on Nrf2 and NF-κB signalling cascades in Wistar Rats. J Pharm Pharmacol 2021; 73(4): 473–486.

https://doi.org/10.1093/jpp/rgaa048

5. Asrani SK, Devarbhavi H, Eaton J, Kamath PS. Burden of liver diseases in the world. J Hepatol 2019; 70(1): 151–171.

https://doi.org/10.1016/j.jhep.2018.09.014

6. Björnsson HK, Björnsson ES. Drug-induced liver injury: Pathogenesis, epidemiology, clinical features, and practical management. Eur J Int Med 2022; 97: 26–31.

https://doi.org/10.1016/j.ejim.2021.10.035

7. Verma G, Sharma V. A Scientific Update on Juglans Regia Linn. Asian J Pharm Res Dev 2020; 8(3): 166-175.

https://doi.org/10.22270/ajprd.v8i3.741

8. Bhardwaj A, Singh A, Patnaik RS, Bhardwaj S. Juglans Regia L: A review of its traditional uses phytochemistry and therapeutic applications. J Pharm Neg Res 2023; 14(1): 11-16.

https://doi.org/10.47750/pnr.2023.14.01.003

9. Mukhtar S, Xiaoxiong Z, Qamer S, Saad M, Mubarik MS, Mahmoud AH, et al. Hepatoprotective activity of silymarin encapsulation against hepatic damage in albino rats. Saudi J Biol Sci 2021; 28(1): 717–723.

https://doi.org/10.1016/j.sjbs.2020.10.063

10. Dwivedi PS, Patil VS, Khanal P, Bhandare VV, Gurav S, Harish DR, et al. System biology-based investigation of Silymarin to trace hepatoprotective effect. Comp Biol Med 2022; 142: 105223.

https://doi.org/10.1016/j.compbiomed.2022.105223

11. Wakim KG. Physiology of the liver. Am J Med 1954; 16(2): 256–271. https://doi.org/10.1016/0002-9343(54)90342-3

12. Singal AK, Arora S, Wong RJ, Satapathy SK, Shah VH, Kuo YF et al. Increasing Burden of Acute-On-Chronic Liver Failure Among Alcohol-Associated Liver Disease in the Young Population in the United States. Am J Gastroenterol 2020; 115(1): 88–95. https://doi.org/10.14309/ajg.0000000000000411

13. Ltaif M, Gargouri M, Soussi A. Protective Effects of A. sativa against Oxidative Stress-Induced Liver Damage in Ovariectomized Mice. BioMed Res Int 2021; 2021(1): 5577498.

https://doi.org/10.1155/2021/5577498

14. Siddique W, Rashid N, Asim S, Firdous A, Hanif A. Comparison of Histoprotective effect of Silymarin and Zinc Sulfate against Hepatotoxicity induced by Isoniazid and Rifampicin combination in animal model. Pak J Med Health Sci 2021; 15(1): 73-78.

15. Dubiwak AD, Damtew TW, Senbetu MW, Yewhalaw D, Asere TG, Nemo G, et al. Hepatoprotective Effect of Corm of Ensete ventricosum (Welw.) Cheesman Extract against Isoniazid and Rifampicin Induced Hepatotoxicity in Swiss Albino Mice. J Toxicol 2021; 2021(1): 4760455.

https://doi.org/10.1155/2021/4760455

16. Lian Y, Zhao J, Xu P, Wang Y, Zhao J, Jia L, et al. Protective effects of metallothionein on isoniazid and rifampicin-induced hepatotoxicity in mice. PloS One 2013; 8(8): e72058.

https://doi.org/10.1371/journal.pone.0072058

17. Eminzade S, Uraz F, Izzettin FV. Silymarin protects liver against toxic effects of anti-tuberculosis drugs in experimental animals. Nutrition and metabolism 2008; 5: 18.

https://doi.org/10.1186/1743-7075-5-18

18. Eidi A, Moghadam JZ, Mortazavi P, Rezazadeh S, Olamafar S. Hepatoprotective effects of Juglans regia extract against CCl4-induced oxidative damage in rats. Pharm Biol 2013; 51(5): 558–565. https://doi.org/10.3109/13880209.2012.749920

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Published

28-02-2026

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Original Articles

How to Cite

1.
Abbas D, Siddique I, Rehman F, Ali SM. Hepatoprotective Effects of Silymarin and Walnut Leaf Extract in Isoniazid and Rifampicin   Induced Hepatotoxicity. Pak Armed Forces Med J [Internet]. 2026 Feb. 28 [cited 2026 Mar. 5];76(1):53-6. Available from: https://pafmj.org/PAFMJ/article/view/12233