Hepatoprotective role of Silybum Marianum against Azithromycin-Induced Histological and Biochemical Changes in Albino Wistar Rats
Keywords:
Silybum marianum, Azithromycin, Superoxide dismutase, Aspartate aminotransferase, Oxidative stressAbstract
Objective: To observe the harmful effects of azithromycin on the liver of albino Wistar rats and analyze the protective effect of silybum marianum against azithromycin-induced histological and biochemical changes in their liver.
Methodology: This experimental study was conducted at the Baqai Medical University, Karachi from December 2023 to March 2024. After ethical approval, 30 male albino Wistar rats were categorized into three groups with 10 rats each. Group A was kept as a control, group B was given azithromycin 200 mg/kg/day for 7 days orally, group C received azithromycin 200 mg/kg/day for 7 days, and silybum marianum (seed extract) 100 mg/kg/day for 21 days orally. After the experiment, all the rats were sacrificed and 3 ml blood was drawn out by cardiac puncture for estimation of liver enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST) & alkaline phosphatase (ALP) and superoxide dismutase (SOD). The liver of the sacrificed rats was removed and stained with hematoxylin and eosin (H&E). Data was analyzed using the Statistical Package for the Social Sciences (SPSS) version 24.
Results: The mean levels of liver enzymes were significantly raised and SOD levels were significantly reduced in group B as compared to group A and C rats. The liver parenchyma of group B rats exhibited significant histopathological changes such as inflammation, hemorrhage, and steatosis, whereas, all group A and most of the group C rats showed no histopathological changes with statistical significance.
Conclusion: Azithromycin-treated rats showed significant biochemical and histopathological changes in the liver parenchyma as compared to control group rats. In azithromycin and silybum marianum-treated rats, the biochemical and histopathological changes were significantly reduced as compared to azithromycin-treated rats alone, indicating the hepatoprotective effects of silybum marianum.
References
1. Sadeghi A, Ketabi Moghadam P, Mangeli F, Salehi N, Rajabnia M. Education case: a case-based approach to overlap syndromes in autoimmune liver disease in patient with ulcerative colitis. Gastroenterol Hepatol Bed Bench. 2022; 15(3):271-81. doi:10.22037/ghfbb.v15i3.2332.
2. Chen VL, Rockey DC, Bjornsson ES, Barnhart H, Hoofnagle JH, Drug-Induced Liver Injury Network Investigators. Incidence of idiosyncratic drug-induced liver injury caused by prescription drugs. Drug Saf. 2025; 48(2):151-60. doi:10.1007/s40264-024-01486-6.
3. Firth A, Prathapan P. Azithromycin: the first broad-spectrum therapeutic. Eur J Med Chem. 2020; 207:112739. doi:10.1016/j.ejmech.2020.112739.
4. Mechery S, Narayanan Nair S, Divya TM, Promod K, Paramba SIN, Ravindran R, et al. Influence of pyrexia on pharmacokinetics of azithromycin and its interaction with tolfenamic acid in goats. Front Vet Sci. 2021; 8:675603. doi:10.3389/fvets.2021.675603.
5. Heidary M, Ebrahimi Samangani A, Kargari A, Kiani Nejad A, Yashmi I, Motahar M, et al. Mechanism of action, resistance, synergism, and clinical implications of azithromycin. J Clin Lab Anal. 2022; 36(6):e24427. doi:10.1002/jcla.24427.
6. Piper BJ, Alinea AA, Wroblewski JR, Graham SM, Chung DY, McCutcheon LRM, et al. A quantitative and narrative evaluation of Goodman and Gilman's pharmacological basis of therapeutics. Pharmacy (Basel). 2019; 8(1):1. doi:10.3390/pharmacy8010001.
7. Karlafti E, Paramythiotis D, Pantazi K, Georgakopoulou VE, Kaiafa G, Papalexis P, et al. Drug-induced liver injury in hospitalized patients during SARS-CoV-2 infection. Medicina (Kaunas). 2022; 58(12):1848. doi:10.3390/medicina58121848.
8. Gillessen A, Schmidt HH. Silymarin as supportive treatment in liver diseases: a narrative review. Adv Ther. 2020; 37(4):1279-301. doi:10.1007/s12325-020-01251-y.
9. Yavuz A, Gobut H, Buyukkasap C, Dikmen K, Bostanci H, Yalcinkaya A, et al. The effect of silymarin given before partial hepatectomy on liver regeneration in rats with ischemic preconditioning during liver resection. Arch Med Res. 2022; 3(3):181-6. doi:10.47482/acmr.1163999.
10. Selc M, Macova R, Babelova A. Novel strategies enhancing bioavailability and therapeutical potential of silibinin for treatment of liver disorders. Drug Des Devel Ther. 2024; 18:4629-59. doi:10.2147/DDDT.S483140.
11. Yavas SE, Yavas O, Ersoy S, Sonmez G. Severe degranulation of mesenteric mast cells in an experimental rat mammary tumor model. Turk J Med Sci. 2024; 54(6):1381-8. doi:10.55730/1300-0144.5921.
12. Kournoutou GG, Dinos G. Azithromycin through the lens of the COVID-19 treatment. Antibiotics (Basel). 2022; 11(8):1063. doi:10.3390/antibiotics11081063.
13. Song IS, Nam SJ, Jeon JH, Park SJ, Choi MK. Enhanced bioavailability and efficacy of silymarin solid dispersion in rats with acetaminophen-induced hepatotoxicity. Pharmaceutics. 2021; 13(5):628. doi:10.3390/pharmaceutics13050628.
14. Omara F, Aziz SA, El-Sheikh SM, Said MAA. Ascorbic acid attenuated the hepatic parenchymal necrosis induced by azithromycin-etoricoxib interaction in rats. J Anim Health Prod. 2021; 9(1):42-8 doi:10.17582/journal.jahp/2021/9.s1.42.48.
15. Ali MAM, Matouk AI, Hamza AA, Amin A, Heeba GH. Gallic and glycyrrhetinic acids prevent azithromycin-induced liver damage in rats by mitigating oxidative stress and inflammation. Sci Rep. 2025; 15(1):9566. doi:10. 1038/s41598-025-93120-3.
16. Dadoub BR, Abdulhadi HL. Hepatoprotective effect of luteolin against azithromycin induced hepatotoxicity. Jundishapur J Microbiol. 2022; 15(1):1417-26. Available from: https://www.researchgate.net/publication/360458246 _Hepatoprotective_Effect_of_Luteolin_against_Azithromycin_Induced_Hepatotoxicity.
17. Hamza RZ, Alaryani FS, Omara F, Said MAA, El-Aziz SAA, El-Sheikh SM. Ascorbic acid ameliorates cardiac and hepatic toxicity induced by azithromycin-etoricoxib drug interaction. Curr Issues Mol Biol. 2022; 44(6):2529-41. doi:10.3390/cimb44060172.
18. Karimian A, Mahmoudi L. Silymarin’s potential in countering drug-induced cardiotoxicity, nephrotoxicity, and hepatotoxicity: a narrative review. TiPST. 2024; 10(1):15-24. doi:10.30476/tips.2024.100638.1220.
19. Radwan DA, Hussin MAE, Mahmoud A. Antioxidant approach of nigella sativa, Vit C and Silymarin for amelioration of azithromycin induced hepatotoxicity: histological, immunohistochemical and biochemical study. ESCTJ. 2021; 9(2):29-45. doi:10.21608/esctj.2021.106959. 1005.
20. Ortiz GX, Lenhart G, Becker MW, Schwambach KH, Tovo CV, Blatt CR. Drug-induced liver injury and COVID-19: a review for clinical practice. World J Hepatol. 2021; 13(9):1143-53. doi:10.4254/wjh.v13.i9.1143.
21. Fotouh A, Abdel-Maguid DS, Abdelhaseib M, Zaki RS, Darweish M. Pathological and pharmacovigilance monitoring as toxicological imputations of azithromycin and its residues in broilers. Vet World. 2024; 17(6):1271-80. doi:10.14202/vetworld.2024.1271-1280.
22. Shiri Aghbash P, Ebrahimzadeh Leylabadlo H, Fathi H, Bahmani M, Chegini R, Bannazadeh Baghi H. Hepatic disorders and COVID-19: from pathophysiology to treatment strategy. Can J Gastroenterol Hepatol. 2022; 2022:4291758. doi:10.1155/2022/4291758.
23. Elhassaneen YA, Afifi TA, Elhefny MA, Bayomi AI. Effect of silybum marianum seeds extract intervention on biochemical parameters, histological changes, and apoptosis and cell cycle of liver tissue in benzo[a]pyrene injected rats. AJFN. 2024; 12(1):1-15. doi:10.12691/ajfn-12-1-1.
24. Siddique W, Rashid N, Faheem MA, Kamal I, Kanwal F, Saghir G. The protective effect of different doses of zinc sulfate and silymarin combination against anti-tuberculosis drug induced toxicity. J Islamabad Med Dental Coll. 2025; 14(1):43-50. doi:10.35787/jimdc.v14i1.1296.
25. Jin Y, Wang X, Chen K, Chen Y, Zhou L, Zeng Y, et al. Silymarin decreases liver stiffness associated with gut microbiota in patients with metabolic dysfunction-associated steatotic liver disease: a randomized, double-blind, placebo-controlled trial. Lipids Health Dis. 2024; 23(1):239. doi:10.1186/s12944-024-02220-y.
26. Marjani M, Fahim F, Sadr M, Kazempour Dizaji M, 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. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC6536020/pdf/GHFBB-12-138.pdf.
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Journal of Sharif Medical & Dental College is licensed and distributed under the terms of Creative Commons Attribution-NonCommercial 4.0 International License.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
