Skip to main content

Advertisement

SpringerLink
Log in

The food supplement coenzyme Q10 and suppression of antitubercular drug-induced hepatic injury in rats: the role of antioxidant defence system, anti-inflammatory cytokine IL-10

  • Original Article
  • Published:
Cell Biology and Toxicology Aims and scope Submit manuscript

Abstract

Introduction

Isoniazid (INH) and rifampicin (RIF), the most common anti-tubercular therapy, causes hepatotoxicity through a multi-step mechanism in certain individuals. The present study was an attempt to evaluate the hepatoprotective effect of coenzyme Q10 against INH + RIF-induced hepatotoxicity in Wistar albino rats.

Methods

Hepatotoxicity was induced by the oral administration of INH + RIF (50 mg/kg b.w. each/day) in normal saline water for 28 days. The hepatoprotective effect of coenzyme Q10 (10 mg/kg b.w./day) was compared with that of the standard drug silymarin (25 mg/kg b.w./day). Animals were sacrificed at the end of the study period, and blood and liver were collected for biochemical, immunological and histological analyses.

Results

Evaluation of biochemical parameters showed that coenzyme Q10 treatment caused significant (P < 0.05) reduction in the elevated levels of serum liver function markers and restored normal levels of total protein, albumin and lipids in INH + RIF-treated rats. Also, it was observed that coenzyme Q10 was able to restore normal levels of enzymic antioxidants, reduced glutathione and lipid peroxidation in the INH + RIF-treated rats. Coenzyme Q10 was found to effectively reduce the extent of liver damage caused due to INH + RIF. In addition, the levels of IL-10 and IL-6 were significantly elevated in the INH + RIF-induced rats treated with CoQ10.

Conclusion

Our study indicates the protective role of coenzyme Q10 in attenuating the hepatotoxic effects of INH + RIF in a rat model and that it could be used as a food supplement during anti-tubercular therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

ATDs:

Antitubercular drugs

CoQ10:

Coenzyme Q10

DAH:

Diacetyl hydrazine

DMN:

Dimethyl nitrosamine

INH:

Isoniazid

MAH:

Monoacetyl hydrazine

RIF:

Rifampicin

References

  • Aithal GP, Ramsay L, Daly AK, Sonchit N, Leathart JBS, Alexander G, et al. Hepatic adducts, circulating antibodies, and cytokine polymorphisms in patients with diclofenac hepatotoxicity. Hepatology. 2004;39(5):1430–40.

    Article  CAS  PubMed  Google Scholar 

  • Alam MA, Rahman MM. Mitochondrial dysfunction in obesity: potential benefit and mechanism of Co-enzyme Q10 supplementation in metabolic syndrome. J Diabetes Metab Disord. 2014;13:60.

    Article  PubMed Central  PubMed  Google Scholar 

  • Attri S, Rana SV, Vaiphei K, Sodhi CP, Katyal R, Goel RC, et al. Isoniazid- and rifampicin-induced oxidative hepatic injury—protection by N-acetylcysteine. Hum Exp Toxicol. 2000;19(9):517–22.

    Article  CAS  PubMed  Google Scholar 

  • Boelsterli UA, Lee KK. Mechanisms of isoniazid-induced idiosyncratic liver injury: emerging role of mitochondrial stress. J Gastroenterol Hepatol. 2014;29(4):678–87.

    Article  CAS  PubMed  Google Scholar 

  • Bourdi M, Masubuchi Y, Reilly TP, Amouzadeh HR, Martin JL, George JW, et al. Protection against acetaminophen-induced liver injury and lethality by interleukin 10: role of inducible nitric oxide synthase. Hepatology. 2002;35(2):289–98.

    Article  CAS  PubMed  Google Scholar 

  • Burk O, Koch I, Raucy J, Hustert E, Eichelbaum M, Brockmöller J, et al. The induction of cytochrome P450 3A5 (CYP3A5) in the human liver and intestine is mediated by the xenobiotic sensors pregnane X receptor (PXR) and constitutively activated receptor (CAR). J Biol Chem. 2004;279(37):38379–85.

    Article  CAS  PubMed  Google Scholar 

  • Byrne JA, Strautnieks SS, Mieli-Vergani G, Higgins CF, Linton KJ, Thompson RJ. The human bile salt export pump: characterization of substrate specificity and identification of inhibitors. Gastroenterology. 2002;123(5):1649–58.

    Article  CAS  PubMed  Google Scholar 

  • Choi H-K, Pokharel YR, Lim SC, Han H-K, Ryu CS, Kim SK, et al. Inhibition of liver fibrosis by solubilized coenzyme Q10: role of Nrf2 activation in inhibiting transforming growth factor-β1 expression. Toxicol Appl Pharmacol. 2009;240(3):377–84.

    Article  CAS  PubMed  Google Scholar 

  • Chowdhury A, Santra A, Kundu S, Mukherjee A, Pandit A, Chaudhuri S, et al. Induction of oxidative stress in antitubercular drug-induced hepatotoxicity. Indian J Gastroenterol. 2001;20(3):97–100.

    CAS  PubMed  Google Scholar 

  • Dong Y, Huang J, Lin X, Zhang S, Jiao Y, Liang T, et al. Hepatoprotective effects of yulangsan polysaccharide against isoniazid and rifampicin-induced liver injury in mice. J Ethnopharmacol. 2014;152(1):201–6.

    Article  CAS  PubMed  Google Scholar 

  • Ellard GA, Gammon PT. Pharmacokinetics of isoniazid metabolism in man. J Pharmacokinet Biopharm. 1976;4(2):83–113.

    Article  CAS  PubMed  Google Scholar 

  • Giannini EG, Testa R, Savarino V. Liver enzyme alteration: a guide for clinicians. Can Med Assoc J. 2005;172(3):367–79.

    Article  Google Scholar 

  • Grosset J, Leventis S. Adverse effects of rifampin. Clin Infect Dis. 1983;5(Supplement 3):S440–6.

    Article  CAS  Google Scholar 

  • Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferases the first enzymatic step in mercapturic acid formation. J Biol Chem. 1974;249(22):7130–9.

    CAS  PubMed  Google Scholar 

  • James LP, Lamps LW, McCullough S, Hinson JA. Interleukin 6 and hepatocyte regeneration in acetaminophen toxicity in the mouse. Biochem Biophys Res Commun. 2003;309(4):857–63.

    Article  CAS  PubMed  Google Scholar 

  • Kanebratt KP, Diczfalusy U, Bäckström T, Sparve E, Bredberg E, Böttiger Y, et al. Cytochrome P450 induction by rifampicin in healthy subjects: determination using the karolinska cocktail and the endogenous CYP3A4 marker 4beta-hydroxycholesterol. Clin Pharmacol Ther. 2008;84(5):589–94.

    Article  CAS  PubMed  Google Scholar 

  • Kettawan A, Takahashi T, Kongkachuichai R, Charoenkiatkul S, Kishi T, Okamoto T. Protective effects of coenzyme Q10 on decreased oxidative stress resistance induced by simvastatin. J Clin Biochem Nutr. 2007;40(3):194–202.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • King J. The dehydrogenases or oxidoreductases— lactate dehydrogenase. In: Van D, editor. Practical clinical enzymology. London: Van Nostrand; 1965. p. 93–193.

  • Lee J, Nakagiri T, Oto T, Harada M, Morii E, Shintani Y, et al. IL-6 amplifier, NF- B-triggered positive feedback for IL-6 signaling, in grafts is involved in allogeneic rejection responses. J Immunol. 2012;189(4):1928–36.

    Article  CAS  PubMed  Google Scholar 

  • 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. Ho W, editor. PLoS ONE. 2013;8(8):e72058.

  • Louis H, Le Moine O, Peny M, Quertinmont E, Fokan D, Goldman M, et al. Production and role of interleukin-10 in concanavalin a-induced hepatitis in mice. Hepatology. 1997;25(6):1382–9.

    Article  CAS  PubMed  Google Scholar 

  • Marklund S, Marklund G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem FEBS. 1974;47(3):469–74.

    Article  CAS  Google Scholar 

  • Martinet W, Knaapen MW, De Meyer GR, Herman AG, Kockx MM. Oxidative DNA damage and repair in experimental atherosclerosis are reversed by dietary lipid lowering. Circ Res. 2001;88(7):733–9.

    Article  CAS  PubMed  Google Scholar 

  • McGeachy MJ, Bak-Jensen KS, Chen Y, Tato CM, Blumenschein W, McClanahan T, et al. TGF-β and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain TH-17 cell-mediated pathology. Nat Immunol. 2007;8(12):1390–7.

    Article  CAS  PubMed  Google Scholar 

  • Moron MS, Depierre JW, Mannervik B. Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim Biophys Acta. 1979;582(1):67–78. BBA - Gen Subj.

    Article  CAS  PubMed  Google Scholar 

  • Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95(2):351–8.

    Article  CAS  PubMed  Google Scholar 

  • Ohkura K, Fukino K, Shinohara Y, Hori H. N-Acetyl transferase 2 polymorphisms associated with isoniazid pharmacodynamics: molecular features for ligand interaction. Anticancer Res. 2010;30(8):3177–80.

    CAS  PubMed  Google Scholar 

  • Pachkoria K, Lucena MI, Crespo E, Ruiz-Cabello F, Lopez-Ortega S, Fernandez MC, et al. Analysis of IL-10, IL-4 and TNF-α polymorphisms in drug-induced liver injury (DILI) and its outcome. J Hepatol. 2008;49(1):107–14.

  • Rae JM, Johnson MD, Lippman ME, Flockhart DA. Rifampin is a selective, pleiotropic inducer of drug metabolism genes in human hepatocytes: studies with cDNA and oligonucleotide expression arrays. J Pharmacol Exp Ther. 2001;299(3):849–57.

    CAS  PubMed  Google Scholar 

  • Rana SV, Pal R, Vaiphie K, Singh K. Effect of different oral doses of isoniazid–rifampicin in rats. Mol Cell Biochem. 2006;289(1–2):39–47.

    Article  CAS  PubMed  Google Scholar 

  • Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG. Selenium: biochemical role as a component of glutathione peroxidase. Science. 1973;179(4073):588–90.

    Article  CAS  PubMed  Google Scholar 

  • Sinha AK. Colorimetric assay of catalase. Anal Biochem. 1972;47(2):389–94.

    Article  CAS  PubMed  Google Scholar 

  • Skakun NP, Shman’ko VV. Synergistic effect of rifampicin on hepatotoxicity of isoniazid. Antibiot Med Biotechnol. 1985;30(3):185–9. Minist Meditsinskoĭ Promyshlennosti SSSR.

    CAS  Google Scholar 

  • Steele MA, Burk RF, DesPrez RM. Toxic hepatitis with isoniazid and rifampin. A meta-analysis. Chest. 1991;99(2):465–71.

    Article  CAS  PubMed  Google Scholar 

  • Steensberg A, Fischer CP, Keller C, Møller K, Pedersen BK. IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans. Am J Physiol Endocrinol Metab. 2003;285(2):E433–7.

    Article  CAS  PubMed  Google Scholar 

  • Steuerwald NM, Foureau DM, Norton HJ, Zhou J, Parsons JC, Chalasani N, et al. Profiles of serum cytokines in acute drug-induced liver injury and their prognostic significance. PLoS One. 2013;8(12):e81974.

    Article  PubMed Central  PubMed  Google Scholar 

  • Vanhoof J, Landewe S, Van Wijngaerden E, Geusens P. High incidence of hepatotoxicity of isoniazid treatment for tuberculosis chemoprophylaxis in patients with rheumatoid arthritis treated with methotrexate or sulfasalazine and anti-tumour necrosis factor inhibitors. Ann Rheum Dis. 2003;62(12):1241–2.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Yue J, Peng R, Yang J, Kong R, Liu J. CYP2E1 mediated isoniazid-induced hepatotoxicity in rats. Acta Pharmacol Sin. 2004;25(5):699–704.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thank VIT University for providing the facilities for conducting this study.

Conflict of interest

The authors declare that there are no conflicts of interest.

Author information

Authors and Affiliations

  1. School of Biosciences and Technology, VIT University, Vellore, Tamil Nadu, 632014, India

    Udhaya Lavinya Baskaran & Evan Prince Sabina

Authors
  1. Udhaya Lavinya Baskaran
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Evan Prince Sabina
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Evan Prince Sabina.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Baskaran, U.L., Sabina, E.P. The food supplement coenzyme Q10 and suppression of antitubercular drug-induced hepatic injury in rats: the role of antioxidant defence system, anti-inflammatory cytokine IL-10. Cell Biol Toxicol 31, 211–219 (2015). https://doi.org/10.1007/s10565-015-9305-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10565-015-9305-x

Keywords

Search

Navigation