Ukr.Biochem.J. 2024; Volume 96, Issue 3, May-Jun, pp. 48-56
doi: https://doi.org/10.15407/ubj96.03.048
Embelin mitigates hepatotoxicity induced by isoniazid and rifampicin in rats
O. F. Mosa
Public Health Department, College of Al-Lieth Health Science,
Umm Al Qura University, Makkah, Saudi Arabia;
e-mail: drosama2030@gmail.com
Received: 09 March 2024; Revised: 29 April 2024;
Accepted: 31 May 2024; Available on-line: 17 June 2024
Isoniazid and rifampicin are reliable drugs against tuberculosis, but while effective, their use is associated with the risk of drug-induced liver damage. Embelin, a natural parabenzoquinone derived from the Embelia ribes plant, has gained attention for its potential therapeutic properties, antioxidant and organ-protective effects. The study aimed to assess the hepatoprotective properties of embelin against liver damage induced by isoniazid and rifampicin in rats. Wistar rats were used, and liver damage was induced by administration of isoniazid (100 mg/kg) and rifampicin (100 mg/kg). Embelin was given at doses of 50, 75, and 100 mg/kg for 21 days. All the drugs were given orally. Serum levels of the oxidative stress markers, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) activity measured by enzymatic assay kits (Elabscience, China), and the levels of tumour necrosis factor-α (TNF-α), interleukins IL-1β and IL-6 measured by ELISA kits (Randox, UK) were estimated. Embelin administration at varying doses effectively restored AST, ALT, ALP, SOD and catalase activity and notably decreased MDA and nitric oxide concentration as well as expression of inflammatory cytokines TNF-α, IL-1β and IL-6 in the serum of animals with drug-induced liver damage. These findings underscore embelin’s hepatoprotective effects, likely attributed to its radical scavenging properties and ability to suppress cytokine production.
Keywords: antioxidant effect, cytokine suppression, embelin, hepatoprotection, isoniazid, rifampicin
References:
- Bessone F, Dirchwolf M, Rodil MA, Razori MV, Roma MG. Review article: drug-induced liver injury in the context of nonalcoholic fatty liver disease – a physiopathological and clinical integrated view. Aliment Pharmacol Ther. 2018;48(9):892-913. PubMed, CrossRef
- Marquez L, Raheja R, Chan-Liston M, Marcinak J, Estilo A, Pineda Salgado L, Jiang J, Chang C, Beninger P. Industry Review of Best Practices for Risk Management of Drug-Induced Liver Injury from Development to Real-World Use. Drug Saf. 2024;47(1):1-22. PubMed, cr id=”https://doi.org/10.1007/s40264-023-01360-x”]
- Lu J, Metushi I, Uetrecht J, Einhorn S, Mann DA, Hanzlik RP, Paul B. Watkins1, LeCluyse EL. Investigation of isoniazid DILI mechanisms in human induced pluripotent stem cell derived hepatocytes. Drug Metab Rev. 2014;45:177.
- Brewer CT. Rifampicin and Isoniazid Induced Liver Injury via the Pregnane X Receptor. FASEB J. 2017;31(S1):lb486-lb486. CrossRef
- Ganeshpurkar A, Saluja AK. The Pharmacological Potential of Rutin. Saudi Pharm J. 2017;25(2):149-164. PubMed, PubMedCentral, CrossRef
- Thabrew MI, Hughes RD, McFarlane IG. Screening of hepatoprotective plant components using a HepG2 cell cytotoxicity assay. J Pharm Pharmacol. 1997;49(11):1132-1135. PubMed, CrossRef
- Ryle PR, Chakraborty J, Thomson AD. doi: 10.1016/0091-3057(83)90220-4.
Biochemical mode of action of a hepatoprotective drug: observations on (+)-catechin. Pharmacol Biochem Behav. 1983;18(Suppl 1):473-478. PubMed, CrossRef - Joshi R, Kamat JP, Mukherjee T. Free radical scavenging reactions and antioxidant activity of embelin: biochemical and pulse radiolytic studies. Chem Biol Interact. 2007;167(2):125-134. PubMed, CrossRef
- Gupta R, Sharma AK, Sharma MC, Gupta RS. Antioxidant activity and protection of pancreatic β-cells by embelin in streptozotocin-induced diabetes. J Diabetes. 2012;4(3):248-256. PubMed, CrossRef
- Prabhu KS, Siveen KS, Kuttikrishnan S, Iskandarani A, Tsakou M, Achkar IW, Therachiyil L, Krishnankutty R, Parray A, Kulinski M, Merhi M, Dermime S, Mohammad RM, Uddin S. Targeting of X-linked inhibitor of apoptosis protein and PI3-kinase/AKT signaling by embelin suppresses growth of leukemic cells. PLoS One. 2017;12(7):e0180895. PubMed, PubMedCentral, CrossRef
- Kumaraswamy HM, Krishna V, Sharath R, Satyanarayan ND, Meghana P, Jain RSK, Prashanth N , Raja Naika H. Potential role of embelin in the prevention of Freund’s adjuvant induced inflammation and ROS. 3 Biotech. 2022;12(1):10. PubMed, PubMedCentral, CrossRef
- Patel RS, Gohil P. Effect of Embelin in middle cerebral artery occlusion-induced focal cerebral ischemia in rats. Oxid Antioxid Med Sci. 2014;3(2):135-139. CrossRef
- Sabina EP, Peter SJ, S P, Geetha A. A comparison of hepatoprotective activity of Bacoside to Silymarin treatment against a combined Isoniazid and Rifampin-induced hepatotoxicity in female Wistar rats. J Histotechnol. 2019;42(3):128-136. PubMed, CrossRef
- Masayasu M, Hiroshi Y. A simplified assay method of superoxide dismutase activity for clinical use. Clin Chim Acta. 1979;92(3):337-342. PubMed, CrossRef
- Sinha AK. Colorimetric assay of catalase. Anal Biochem. 1972;47(2):389-394. PubMed, CrossRef
- Ohkawa H, Ohishi N, Yagi K. Reaction of linoleic acid hydroperoxide with thiobarbituric acid. J Lipid Res. 1978;19(8):1053-1057. PubMed, CrossRef
- Moshage H, Kok B, Huizenga JR, Jansen PL. Nitrite and nitrate determinations in plasma: a critical evaluation. Clin Chem. 1995;41(6):892-896. PubMed, CrossRef
- Zhuang X, Li L, Liu T, Zhang R, Yang P, Wang X, Dai L. Mechanisms of isoniazid and rifampicin-induced liver injury and the effects of natural medicinal ingredients: A review. Front Pharmacol. 2022;13:1037814. PubMed, PubMedCentral, CrossRef
- Mani S, Tyagi S, Pal KV, Jaiswal H, Jain A, Gulati A, et al. Drug-Induced Oxidative Stress and Cellular Toxicity. In: Free Radical Biology and Environmental Toxicity. Springer; 2022:73-113. CrossRef
- Garcia-Cortes M, Robles-Diaz M, Stephens C, Ortega-Alonso A, Lucena MI, Andrade RJ. Drug induced liver injury: an update. Arch Toxicol. 2020;94(10):3381-3407. PubMed, CrossRef
- Akakpo JY, Ramachandran A, Jaeschke H. Novel strategies for the treatment of acetaminophen hepatotoxicity. Expert Opin Drug Metab Toxicol. 2020;16(11):1039-1050. PubMed, PubMedCentral, CrossRef
- Jewad AM, Jihad IA. Role of heart failure in variation of serum ALT, AST, ALP, bilirubin and electrolytes. Biochem Cell Arch. 2021;21(2):3415-3421.
- Jomova K, Raptova R, Alomar SY, Alwasel SH, Nepovimova E, Kuca K, Valko M. Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging. Arch Toxicol. 2023;97(10):2499-2574. PubMed, PubMedCentral, CrossRef
- Cavalli G, Colafrancesco S, Emmi G, Imazio M, Lopalco G, Maggio MC, Sota J, Dinarello CA. Interleukin 1α: a comprehensive review on the role of IL-1α in the pathogenesis and treatment of autoimmune and inflammatory diseases. Autoimmun Rev. 2021;20(3):102763. PubMed, CrossRef
- Niculet E, Chioncel V, Elisei AM, Miulescu M, Buzia OD, Nwabudike LC, Craescu M, Draganescu M, Bujoreanu F, Marinescu E, Arbune M, Radaschin DS, Bobeica C, Nechita A, Tatu A. Multifactorial expression of IL-6 with update on COVID-19 and the therapeutic strategies of its blockade (Review). Exp Ther Med. 2021;21(3):263. PubMed, PubMedCentral, CrossRef
- Gantner BN, LaFond KM, Bonini MG. Nitric oxide in cellular adaptation and disease. Redox Biol. 2020;34:101550. PubMed, PubMedCentral, CrossRef
- Joshi R, Kamat JP, Mukherjee T. Free radical scavenging reactions and antioxidant activity of embelin: biochemical and pulse radiolytic studies. Chem Biol Interact. 2007;167(2):125-134. PubMed, CrossRef
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