Hepatoprotective Effects of Milkfish (Chanos chanos) Oil and Silymarin Against Isoniazid–Rifampicin-Induced Liver Injury in Rats
Heru Sasongko(1*), Mikael Hovhanness(2), Arinda Handiyah Sawitri(3), Aulia Hanundita Maharani(4), Delia Putri Hedianti(5), Josua Arianto Hutasoit(6), Lathyfa Asyraq(7), Listiyana Ika Safitri(8), Lois Elda Zai(9), Sutarno Sutarno(10)
(1) Department of Pharmacy, Vocational School, Sebelas Maret University, Jl. Ir. Sutami 36A Surakarta, Central Java
(2) Department of Pharmacy, Vocational School, Sebelas Maret University, Jl. Ir. Sutami 36A Surakarta, Central Java
(3) Department of Pharmacy, Vocational School, Sebelas Maret University, Jl. Ir. Sutami 36A Surakarta, Central Java
(4) Department of Pharmacy, Vocational School, Sebelas Maret University, Jl. Ir. Sutami 36A Surakarta, Central Java
(5) Department of Pharmacy, Vocational School, Sebelas Maret University, Jl. Ir. Sutami 36A Surakarta, Central Java
(6) Department of Pharmacy, Vocational School, Sebelas Maret University, Jl. Ir. Sutami 36A Surakarta, Central Java
(7) Department of Pharmacy, Vocational School, Sebelas Maret University, Jl. Ir. Sutami 36A Surakarta, Central Java
(8) Department of Pharmacy, Vocational School, Sebelas Maret University, Jl. Ir. Sutami 36A Surakarta, Central Java
(9) Department of Pharmacy, Vocational School, Sebelas Maret University, Jl. Ir. Sutami 36A Surakarta, Central Java
(10) Department of Biology, Faculty of Mathematics and Natural Science, Sebelas Maret University, Jl. Ir Sutami No.36A Surakarta, Central Java
(*) Corresponding Author
Abstract
The objectives of the present research were to assess the hepatoprotective activities of milkfish oil (MFO) and silymarin (SL) against rifampicin (RFP) and isoniazid (INH) induced hepatotoxicity. Rats were divided into seven groups: normal control, negative control (INH+RFP), silymarin alone (50 mg/kg BW/day), low-dose MFO (MFO-L), high-dose MFO (MFO-H), low-dose combination (SL+MFO-L), and high-dose combination (SL+MFO-H). Rats receiving RFP and INH showed raised liver enzymes and typical signs of hepatotoxicity. Analyzed parameters comprised proinflammatory mediators (tumor necrosis factor-alpha and interleukin-6), antioxidant markers (catalase, glutathione, malondialdehyde, and superoxide dismutase), cytochrome P450, total protein, aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin and bilirubin. Treatment with a combination of MFO plus SL remarkably decreased hepatic enzyme activities, oxidative stress and inflammation, and suggested a prevention effect against the drug-induce liver injury.
Keywords
Full Text:
PDFReferences
Akkerman, O. W., Dijkwel, R. D. C., Kerstjens, H. A. M., van der Werf, T. S., Srivastava, S., Sturkenboom, M. G. G., & Bolhuis, M. S. (2023). Isoniazid and rifampicin exposure during treatment in drug-susceptible TB. The International Journal of Tuberculosis and Lung Disease, 27(10), 772–777. https://doi.org/10.5588/ijtld.22.0698
Aziza, I. N., Maulana, I. T., & Sadiyah, E. R. (2015). Perbandingan Kandungan Omega 3 Dalam Minyak Ikan Bandeng (Chanos chanos
Forsskal) Yang Segar Dengan Ikan Bandeng Yang Dikeringkan Di Pasar. https://api.semanticscholar.org/CorpusID:101576098
Babu, P. S., Krishna, V., Bhavya, D. C., Babu, P. S., Krishna, V., & Bhavya, D. C. (2023). Hepatoprotective activity of Tridecan-1-ol isolatedfrom Flaveria trinervia (Speng). C. Mohr. GSC Biological and Pharmaceutical Sciences, 22(3), Article 3. https://doi.org/10.30574/gscbps.2023.22.3.0093
Bhatt, A., Quazi Syed, Z., & Singh, H. (2023). Converging Epidemics: A Narrative Review of Tuberculosis (TB) and Human Immunodeficiency Virus (HIV) Coinfection. Cureus, 15(10), e47624. https://doi.org/10.7759/cureus.47624
Biswas, A., Santra, S., Bishnu, D., Dhali, G. K., Chowdhury, A., & Santra, A. (2020). Isoniazid and Rifampicin Produce Hepatic Fibrosis through an Oxidative Stress-Dependent Mechanism. International Journal of Hepatology, 2020, e6987295. https://doi.org/10.1155/2020/6987295
Borgonovi, S. M., Iametti, S., & Di Nunzio, M. (2023). Docosahexaenoic Acid as Master Regulator of Cellular Antioxidant Defenses: A Systematic Review. Antioxidants, 12(6), Article 6. https://doi.org/10.3390/antiox12061283
da Silva, E. P., Nachbar, R. T., Levada-Pires, A. C., Hirabara, S. M., & Lambertucci, R. H. (2016). Omega-3 fatty acids differentially modulate enzymatic anti-oxidant systems in skeletal muscle cells. Cell Stress & Chaperones, 21(1), 87–95. https://doi.org/10.1007/s12192-015-0642-8
Djohan, R., Harjanti, A., & Pendrianto, P. (2023). Protective Effect of Andropraphis Paniculata Aqueous Extract (EAAp) Against Isoniazid and Rifampicin-Induced Rat Liver Damage. Jurnal Health Sains, 4(8), Article 8. https://doi.org/10.46799/jhs.v4i8.1052
Fazelian, S., Moradi, F., Agah, S., Hoseini, A., Heydari, H., Morvaridzadeh, M., Omidi, A., Pizarro, A. B., Ghafouri, A., & Heshmati, J. (2021). Effect of omega-3 fatty acids supplementation on cardio-metabolic and oxidative stress parameters in patients with chronic kidney disease: A systematic review and meta-analysis. BMC Nephrology, 22, 160. https://doi.org/10.1186/s12882-021-02351-9
Giustarini, D., Milzani, A., Dalle-Donne, I., & Rossi, R. (2023). How to Increase Cellular Glutathione. Antioxidants, 12(5), 1094. https://doi.org/10.3390/antiox12051094
Guan, X. (2023). Glutathione and glutathione disulfide – their biomedical and pharmaceutical applications. Medicinal Chemistry Research, 32(9), 1972–1994. https://doi.org/10.1007/s00044-023-03116-9
Jabbari, A., Alani, B., Arjmand, A., Mazoochi, T., Kheiripour, N., & Ardjmand, A. (2023). Silymarin pretreatment protects against ethanol-induced memory impairment: Biochemical and histopathological evidence. Journal of Chemical Neuroanatomy, 132, 102310. https://doi.org/10.1016/j.jchemneu.2023.102310
Jang, D., Lee, A.-H., Shin, H.-Y., Song, H.-R., Park, J.-H., Kang, T.-B., Lee, S.-R., & Yang, S.-H. (2021). The Role of Tumor Necrosis Factor Alpha (TNF-α) in Autoimmune Disease and Current TNF-α Inhibitors in Therapeutics. International Journal of Molecular Sciences, 22(5), 2719. https://doi.org/10.3390/ijms22052719
Jeong, Y.-J., Park, J. S., Kim, H. W., Min, J., Ko, Y., Oh, J. Y., Lee, E. H., Yang, B., Lee, M. K., Kim, Y. S., Chang, J. H., Jegal, Y., Lee, S. S., Kim, J. S., & Koo, H.-K. (2023). Deaths from tuberculosis: Differences between tuberculosis-related and non-tuberculosis-related deaths. Frontiers in Public Health, 11, 1207284. https://doi.org/10.3389/fpubh.2023.1207284
Karimi, G., Vahabzadeh, M., Lari, P., Rashedinia, M., & Moshiri, M. (2011). “Silymarin”, a Promising Pharmacological Agent for Treatment of Diseases. Iranian Journal of Basic Medical Sciences, 14(4), 308–317.
Khura, J., Khurana, T. R., Anubhuti, Mehra, S., & Singh, P. (2019). Evaluation of Pro-Inflammatory Markers IL-6 and TNF-a and their Correlation with Non-Alcoholic Fatty Liver Disease. Journal of Advanced Research in Medicine (E-ISSN: 2349-7181 & P-ISSN: 2394-7047), 6(2), Article 2.
Lei, S., Gu, R., & Ma, X. (2021). Clinical perspectives of isoniazid-induced liver injury. Liver Research, 5(2), 45–52. https://doi.org/10.1016/j.livres.2021.02.001
Li, X., Zhang, H., Xu, L., Jin, Y., Luo, J., Li, C., Zhao, K., Zheng, Y., Yu, D., & Zhao, Y. (2021). miR-15a-3p Protects Against Isoniazid-Induced Liver Injury via Suppressing N-Acetyltransferase
2 Expression. Frontiers in Molecular Biosciences, 8. https://doi.org/10.3389/fmolb.2021.752072
Liu, D., Ren, Y., Zhong, S., & Xu, B. (2024). New Insight into Utilization of Fish By-Product Proteins and Their Skin Health Promoting Effects. Marine Drugs, 22(5), Article 5. https://doi.org/10.3390/md22050215
Masrukan, Yanti, R., Setyaningsih, W., & Raharjo, S. (2024). Effect of deodorization method on the physico-chemical and nutritional properties of the refined milkfish (Channos channos) by-product oil. Indonesian Journal of Pharmacy. https://doi.org/10.22146/ijp.13730
Moman, R. N., Gupta, N., & Varacallo, M. (2024). Physiology, Albumin. In StatPearls. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK459198/
Mukhtar, S., Xiaoxiong, Z., Qamer, S., Saad, M., Mubarik, M. S., Mahmoud, A. H., & Mohammed, O. B. (2021). Hepatoprotective activity of silymarin encapsulation against hepatic damage in albino rats. Saudi Journal of Biological Sciences, 28(1), 717–723. https://doi.org/10.1016/j.sjbs.2020.10.063
Murthy, L. N., Padiyar, P. A., Madhusudana Rao, B., Asha, K. K., Jesmi, D., Girija, P. G., Prasad, M. M., & Ravishankar, C. N. (2016). Nutritional Profile and Heavy Metal Content of Cultured Milkfish (Chanos chanos). http://krishi.icar.gov.in/jspui/handle/123456789/14671
Ndrepepa, G. (2021). Aspartate aminotransferase and cardiovascular disease—A narrative review. Journal of Laboratory and Precision Medicine, 6(0), Article 0. https://doi.org/10.21037/jlpm-20-93
Okada, A. (2023). Chapter 7 - Cardio-hepatology: Liver function tests in heart failure. In T. Taniguchi & S. S. Lee (Eds.), Cardio-Hepatology (pp. 105–113). Academic Press. https://doi.org/10.1016/B978-0-12-817394-7.00006-1
Okiljević, B., Martić, N., Govedarica, S., Andrejić Višnjić, B., Bosanac, M., Baljak, J., Pavlić, B., Milanović, I., & Rašković, A. (2024). Cardioprotective and Hepatoprotective Potential of Silymarin in Paracetamol-Induced Oxidative Stress. Pharmaceutics, 16(4), Article 4. https://doi.org/10.3390/pharmaceutics16040520
Pratiwi, R. D., Alisjahbana, B., Subronto, Y. W., Priyanta, S., & Suharna, S. (2025). Implementation of an information system for tuberculosis in healthcare facilities in Indonesia: evaluation of its effectiveness and challenges. Archives of Public Health, 83(1), 22. https://doi.org/10.1186/s13690-025-01507-5
Ransy, C., Vaz, C., Lombès, A., & Bouillaud, F. (2020). Use of H2O2 to Cause Oxidative Stress, the Catalase Issue. International Journal of Molecular Sciences, 21(23), 9149. https://doi.org/10.3390/ijms21239149
Refaie, A. A., Ramadan, A., Sabry, N. M., Khalil, W. K. B., & Mossa, A.-T. H. (2021). Synthetic Insecticide Fipronil Induced Over Gene Expression, DNA and Liver Damage in Female Rats: The Protective Role of Fish Oil. Egyptian Journal of Chemistry, 64(5), 2325–2336. https://doi.org/10.21608/ejchem.2021.58506.3264
Sasongko, H., Nurrochmad, A., Nugroho, A. E., & Rohman, A. (2022). Indonesian freshwater fisheries’ oil for health and nutrition applications: A narrative review. Food Research, 6(2), 501-511. https://doi.org/10.26656/fr.2017.6(2).362
Sasongko, H., Nugroho, A. E., Nurrochmad, A., & Rohman, A. (2024). Nephroprotective Effect of Milkfish, Patin, and Snakehead Fish Oil by Suppressing Inflammation and Oxidative Stress in Diabetic Rats. Indonesian Journal of Pharmacy, 35(1), 63-73. https://doi.org/10.22146/ijp.7725
Simpson, L. J., Reader, J. S., & Tzima, E. (2020). Mechanical Regulation of Protein Translation in the Cardiovascular System. Frontiers in Cell and Developmental Biology, 8, 34. https://doi.org/10.3389/fcell.2020.00034
Somasundaram, S., Ram, A., & Sankaranarayanan, L. (2014). Isoniazid and Rifampicin as Therapeutic Regimen in the Current Era: A Review. Journal of Tuberculosis Research, 2(1), Article 1. https://doi.org/10.4236/jtr.2014.21005
Surai, P. F. (2015). Silymarin as a Natural Antioxidant: An Overview of the Current Evidence and Perspectives. Antioxidants, 4(1), 204–247. https://doi.org/10.3390/antiox4010204
Taleb, A., Ahmad, K. A., Ihsan, A. U., Qu, J., Lin, N., Hezam, K., Koju, N., Hui, L., & Qilong, D. (2018). Antioxidant effects and mechanism of silymarin in oxidative stress induced cardiovascular diseases. Biomedicine & Pharmacotherapy, 102, 689–698. https://doi.org/10.1016/j.biopha.2018.03.140
Tanaka, T., Narazaki, M., & Kishimoto, T. (2014). IL-6 in Inflammation, Immunity, and Disease. Cold Spring Harbor Perspectives in Biology, 6(10), a016295. https://doi.org/10.1101/cshperspect.a016295
Tekin, S., & Seven, E. (2022). Assessment of serum catalase, reduced glutathione, and superoxide dismutase activities and malondialdehyde levels in keratoconus patients. Eye, 36(10), 2062–2066. https://doi.org/10.1038/s41433-021-01753-1
Trefts, E., Gannon, M., & Wasserman, D. H. (2017). The liver. Current Biology : CB, 27(21), R1147–R1151. https://doi.org/10.1016/j.cub.2017.09.019
Tufoni, M., Zaccherini, G., Caraceni, P., & Bernardi, M. (2020). Albumin: Indications in chronic liver disease. United European Gastroenterology Journal, 8(5), 528. https://doi.org/10.1177/2050640620910339
Wang, D., Cai, X., Lin, X., Zheng, J., Wu, Y., & Peng, X. (2022). Hepatoprotective drugs for prevention of liver injury resulting from anti-tuberculosis treatment: A meta-analysis of cohort studies. Infectious Medicine, 1(3), 154–162. https://doi.org/10.1016/j.imj.2022.07.003
Wu, G., Lupton, J. R., Turner, N. D., Fang, Y.-Z., & Yang, S. (2004). Glutathione Metabolism and Its Implications for Health. The Journal of Nutrition, 134(3), 489–492. https://doi.org/10.1093/jn/134.3.489
Zhang, Q., Piao, C., Xu, J., Jiao, Z., Ge, Y., Liu, X., Ma, Y., & Wang, H. (2019). Comparative study on protective effect of hydrogen rich saline and adipose-derived stem cells on hepatic ischemia-reperfusion and hepatectomy injury in swine. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 120, 109453. https://doi.org/10.1016/j.biopha.2019.109453
Zheng, M., Liu, Y., Zhang, G., Yang, Z., Xu, W., & Chen, Q. (2023). The Applications and Mechanisms of Superoxide Dismutase in Medicine, Food, and Cosmetics. Antioxidants, 12(9), 1675. https://doi.org/10.3390/antiox12091675
Zhuang, X., Li, L., Liu, T., Zhang, R., Yang, P., Wang, X., & Dai, L. (2022). Mechanisms of isoniazid and rifampicin-induced liver injury and the effects of natural medicinal ingredients: A review. Frontiers in Pharmacology, 13. https://www.frontiersin.org/articles/10.3389/fphar.2022.1037814
Article Metrics
Refbacks
- There are currently no refbacks.
Copyright (c) 2026 Majalah Obat Tradisional

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
.png)
.png)


