Herbo-vitamin medicine Livogrit Vital ameliorates isoniazid induced liver injury (IILI) in human liver (HepG2) cells by decreasing isoniazid accumulation and oxidative stress driven hepatotoxicity.

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  • Additional Information
    • Source:
      Publisher: BioMed Central Country of Publication: England NLM ID: 101761232 Publication Model: Electronic Cited Medium: Internet ISSN: 2662-7671 (Electronic) Linking ISSN: 26627671 NLM ISO Abbreviation: BMC Complement Med Ther Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : BioMed Central, [2020]-
    • Subject Terms:
      Isoniazid* ; Oxidative Stress*/drug effects ; Chemical and Drug Induced Liver Injury*/drug therapy ; Antitubercular Agents*; Humans ; Hep G2 Cells ; Plant Extracts/pharmacology ; Apoptosis/drug effects
    • Abstract:
      Background: Tuberculosis (TB) is a leading cause of infection related mortality. Isoniazid is one of the frontline drugs for anti-TB therapy. Hepatotoxicity induced by isoniazid is a major cause of drug-discontinuation which may lead to development of resistant TB or increased mortality.
      Purpose: To characterize pharmacological properties of plant-based prescription medicine, Livogrit Vital (LVV) against isoniazid-induced liver injury (IILI) using HepG2 cells.
      Method: Phytometabolite characterization of LVV was performed by High-performance liquid chromatography (HPLC). The effects of LVV on cytosafety, IC 50 shift, oxidative stress, ER stress, apoptosis, liver injury markers, and accumulation of isoniazid and hydrazine was performed on HepG2 cells induced with isoniazid. Silymarin was used as the positive control.
      Results: HPLC based phytometabolite characterization of LVV revealed the presence of several anti-oxidant, anti-apoptotic, and hepatoprotective compounds. In isoniazid-induced HepG2 cells, LVV reduced cytotoxicity of isoniazid and shifted its IC 50 value. Treatment with LVV reduced ROS generation and lipid peroxidation; enhanced GSH enzyme levels in isoniazid-induced HepG2 cells. As per the mechanistic evaluation, LVV modulated gene expression level of Caspase-3, FGF21, and IRE-1α. LVV treatment also normalized isoniazid-induced elevated Caspase-3 activity and cPARP1 protein levels, indicating its potentials to regulate liver cell apoptosis. Concomitantly, biomarkers of hepatotoxicity, ALT and GGT, also decreased by LVV treatment. Interestingly, LVV treatment reduced intracellular accumulation of isoniazid and its toxic metabolite hydrazine, in isoniazid-stimulated HepG2 cells.
      Conclusion: Treatment of hepatic cells with the herbo-vitamin medicine, Livogrit Vital, regulates IILI by modulation of oxidative and ER stress, apoptosis, and bioaccumulation of isoniazid and hydrazine. Collectively, Livogrit Vital could well be explored as an adjuvant hepatoprotective agent alongwith anti-TB medicines.
      (© 2024. The Author(s).)
    • References:
      Chem Biodivers. 2022 Jul;19(7):e202200158. (PMID: 35604399)
      Toxins (Basel). 2023 Jul 12;15(7):. (PMID: 37505724)
      Chem Commun (Camb). 2020 Nov 25;56(91):14183-14186. (PMID: 33107880)
      Front Pharmacol. 2022 Oct 10;13:1037814. (PMID: 36299895)
      Lancet Microbe. 2023 Jan;4(1):e20. (PMID: 36521512)
      Bioengineered. 2022 Apr;13(4):10811-10826. (PMID: 35485140)
      Int J Mol Sci. 2020 May 25;21(10):. (PMID: 32466226)
      Tuberculosis (Edinb). 2019 May;116S:S66-S70. (PMID: 31076322)
      Oxid Med Cell Longev. 2022 Jun 6;2022:8494076. (PMID: 35707277)
      Pharm Biol. 2016 Nov;54(11):2664-2673. (PMID: 27159805)
      Naunyn Schmiedebergs Arch Pharmacol. 2020 Dec;393(12):2473-2480. (PMID: 33052426)
      J Appl Toxicol. 2015 Dec;35(12):1427-32. (PMID: 26095833)
      J Ethnopharmacol. 2023 Jun 28;310:116387. (PMID: 36948265)
      Exp Ther Med. 2019 May;17(5):4289-4293. (PMID: 30988801)
      Hum Exp Toxicol. 2016 Dec;35(12):1252-1263. (PMID: 26801986)
      Heliyon. 2021 Jul 02;7(7):e07465. (PMID: 34278037)
      Toxicol Rep. 2022 Apr 29;9:1056-1064. (PMID: 35571233)
      Hum Exp Toxicol. 2017 Jul;36(7):709-717. (PMID: 27461011)
      PLoS One. 2013 Aug 13;8(8):e72058. (PMID: 23967274)
      Biomed Pharmacother. 2023 Apr;160:114309. (PMID: 36709598)
      Front Nutr. 2022 Oct 20;9:989311. (PMID: 36337656)
      Ther Adv Drug Saf. 2022 Oct 8;13:20420986221127503. (PMID: 36225945)
      Pharm Biol. 2014 Jan 10;:. (PMID: 24405044)
      Toxicol Res (Camb). 2016 Apr 4;5(3):963-972. (PMID: 30090405)
      Drug Des Devel Ther. 2018 Oct 18;12:3525-3533. (PMID: 30425454)
      Prev Nutr Food Sci. 2014 Jan;19(1):19-26. (PMID: 24772405)
      Molecules. 2020 Oct 21;25(20):. (PMID: 33096687)
      Front Pharmacol. 2020 Mar 25;11:288. (PMID: 32269524)
      Exp Anim. 2021 Feb 6;70(1):54-62. (PMID: 32963203)
      Toxicol Mech Methods. 2010 Jun;20(5):242-51. (PMID: 20433247)
      Hepatology. 2014 Sep;60(3):977-89. (PMID: 24590984)
      Life Sci. 2021 Aug 1;278:119583. (PMID: 33957170)
      J Nat Sci Biol Med. 2013 Jan;4(1):63-7. (PMID: 23633837)
      J Pharm Pharmacol. 2021 Mar 8;73(4):473-486. (PMID: 33793834)
      J Biochem Mol Toxicol. 2019 Sep;33(9):e22369. (PMID: 31332904)
      Lancet Respir Med. 2022 Jun;10(6):537-539. (PMID: 35659006)
      Hum Exp Toxicol. 2012 Aug;31(8):788-97. (PMID: 22318308)
      Iran J Basic Med Sci. 2023 Apr;26(4):478-485. (PMID: 37009010)
      Drug Chem Toxicol. 2022 Mar;45(2):850-860. (PMID: 32543916)
      Int J Mol Sci. 2021 Dec 04;22(23):. (PMID: 34884942)
    • Contributed Indexing:
      Keywords: Hepatotoxicity; IILI; Isoniazid; Oxidative stress; Tuberculosis; Vitamins
    • Accession Number:
      V83O1VOZ8L (Isoniazid)
      0 (Antitubercular Agents)
      0 (Plant Extracts)
    • Publication Date:
      Date Created: 20241108 Date Completed: 20241109 Latest Revision: 20241116
    • Publication Date:
      20241116
    • Accession Number:
      PMC11545855
    • Accession Number:
      10.1186/s12906-024-04685-x
    • Accession Number:
      39516811