Skip to main content
Log in

Anti-inflammatory and ameliorative effects of gallic acid on fluoxetine-induced oxidative stress and liver damage in rats

  • Original article
  • Published:
Pharmacological Reports Aims and scope Submit manuscript

Abstract

Background

Fluoxetine-induced liver damage is a cause of chronic liver disease. In the present study the hepatoprotective effects of gallic acid against fluoxetine-induced liver damage were examined.

Methods

Forty-eight male rats were divided into six groups as follow: group 1, the control group; group 2, rats receiving fluoxetine (24 mg/kg bw daily, po) without treatment; group 3, rats receiving 24 mg/kg bw fluoxetine, treated with 50 mg/kg bw silymarin and groups 4, 5, and 6 in which gallic acid (50, 100, and 200 mg/kg bw, po, respectively) was prescribed after the consumption of fluoxetine. The histopathological changes of hepatic tissues were checked out.

Results

Fluoxetine caused a significant increase in the levels of serum glutamate oxaloacetate transaminase (GOT), serum glutamate pyruvate transaminase (GPT), lipid profiles, urea, fasting blood sugar (FBS), creatinine (Cr), protein carbonyl (PC) content, malondialdehyde (MDA), and liver TNF-α as an inflammatory element. Also, the obtained results of group 2 revealed a significant decline in ferric reducing ability of plasma (FRAP), liver catalase (CAT), superoxide dismutase (SOD), and vitamin C levels. The treatment with gallic acid showed significant ameliorations in abnormalities of fluoxetine-induced liver injury as represented by the improvement of hepatic CAT, SOD activities, vitamin C levels, serum biochemical parameters, and histopathological changes, in addition to the recovery of antioxidant defense system status.

Conclusions

Gallic acid has inhibitory effects on fluoxetine-induced liver damage. The effect of gallic acid is derived from free radical scavenging properties and the anti-inflammatory effect related to TNF-α.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Insel TR, Charney DS. Research on major depression: strategies and priorities. JAMA 2003;289:3167–8.

    Article  PubMed  Google Scholar 

  2. Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJ. Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet 2006;367:1747–57.

    Article  PubMed  Google Scholar 

  3. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PloS Med 2006;3:e442.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Freeborough A, Kimpton J. Discovering new genetic and psychosocial pathways in Major Depressive Disorder: the NewMood project. Psychiatr Danub 2011;23:S138–41.

    PubMed  Google Scholar 

  5. Schneier FR, Liebowitz MR, Davies SO, Fairbanks J, Hollander E, Campeas R, et al. Fluoxetine in panic disorder. J Clin Psychopharmacol 1990;10:119–21.

    Article  CAS  PubMed  Google Scholar 

  6. Levine LR. Fluoxetine in the treatment of bulimia nervosa. Arch Gen Psychiatry 1992;49:139–47.

    Article  Google Scholar 

  7. Su T-P, Schmidt PJ, Danaceau MA, Tobin MB, Rosenstein DL, Murphy DL, et al. Fluoxetine in the treatment of premenstrual dysphoria. Neuropsychopharmacology 1997;16:346.

    Article  CAS  PubMed  Google Scholar 

  8. Amsterdam JD, Garcia-Espana F, Fawcett J, Quitkin FM, Reimherr FW, Rosenbaum JF, et al. Blood pressure changes during short-term fluoxetine treatment. J Clin Psychopharmacol 1999; 19:9–14.

    Article  CAS  PubMed  Google Scholar 

  9. Raeder MB, Bjelland I, Steen VM. Obesity, dyslipidemia, and diabetes with selective serotonin reuptake inhibitors: the Hordaland Health Study. J Clin Psychiatry 2006;67:1974–82.

    Article  CAS  PubMed  Google Scholar 

  10. Nabavi SM, Nabavi SF, Eslami S, Moghaddam AH. In vivo protective effects of quercetin against sodium fluoride-induced oxidative stress in the hepatic tissue. Food Chem 2012;132:931–5, doi:https://doi.org/10.1016/j.foodchem.2011.11.070.

    Article  CAS  Google Scholar 

  11. Shanthakumari D, Srinivasalu S, Subramanian S. Effect of fluoride intoxication on lipidperoxidation and antioxidant status in experimental rats. Toxicology 2004;204:219–28.

    Article  CAS  PubMed  Google Scholar 

  12. Heidarian E, Rafieian-Kopaei M, Khoshdel A, Bakhshesh M. Metabolic effects of berberine on liver phosphatidate phosphohydrolase in rats fed on high lipogenic diet: an additional mechanism for the hypolipidemic effects of berberine. Asian Pac J Trop Biomed 2014;4:S429–35.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Heidarian E, Saffari J, Jafari-Dehkordi E. Hepatoprotective action of Echinophora platyloba DC leaves against acute toxicity of acetaminophen in rats. J Diet Suppl 2014; 11:53–63.

    Article  PubMed  Google Scholar 

  14. Heidarian E, Keloushadi M, Ghatreh-Samani K, Valipour P. The reduction of IL-6 gene expression, pAKT, pERK1/2, pSTAT3 signaling pathways and invasion activity by gallic acid in prostate cancer PC3 cells. Biomed Pharmacother 2016;84:264–9.

    Article  CAS  PubMed  Google Scholar 

  15. Eslami AC, Pasanphan W, Wagner BA, Buettner GR. Free radicals produced by the oxidation of gallic acid: an electron paramagnetic resonance study. Chem Cent J 2010;4:1–4.

    Article  CAS  Google Scholar 

  16. Nabavi SF, Habtemariam S, Jafari M, Sureda A, Nabavi SM. Protective role of gallic acid on sodium fluoride induced oxidative stress in rat brain. Bull Environ Contam Toxicol 2012;89:73–7.

    Article  CAS  PubMed  Google Scholar 

  17. Anand K, Singh B, Saxena A, Chandan B, Gupta V, Bhardwaj V. 3, 4, 5-trihydroxy benzoic acid (gallic acid), the hepatoprotective principle in the fruits ofterminalia belerica-bioassay guided activity. Pharmacol Res 1997;36:315–21.

    Article  CAS  PubMed  Google Scholar 

  18. Inkielewicz-Stępniak I. Impact of fluoxetine on liver damage in rats. Pharmacol Rep 2011;63:441–7.

    Article  PubMed  Google Scholar 

  19. Wills P, Asha V. Protective effect of Lygodiumflexuosum (L.) Sw. extract against carbon tetrachloride-induced acute liver injury in rats. J Ethnopharmacol 2006;108:320–6.

    Article  CAS  PubMed  Google Scholar 

  20. Jadon A, Bhadauria M, Shukla S. Protective effect of Terminalia belerica Roxb. and gallic acid against carbon tetrachloride induced damage in albino rats. J Ethnopharmacol 2007; 109:214–8.

    Article  CAS  PubMed  Google Scholar 

  21. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;18:499–502.

    CAS  PubMed  Google Scholar 

  22. Heidarian E, Soofiniya Y. Hypolipidemic and hypoglycemic effects of aerial part of Cynara scolymus in streptozotocin-induced diabetic rats. J Med Plants Res 2011;5:2717–23.

    CAS  Google Scholar 

  23. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976;72:248–54.

    Article  CAS  PubMed  Google Scholar 

  24. Reznick AZ, Packer L. Oxidative damage to proteins: spectrophotometric method for carbonyl assay. Methods Enzymol 1994;233:357–63.

    Article  CAS  PubMed  Google Scholar 

  25. Agarwal R, Chase SD. Rapid, fluorimetric-liquid chromatographic determination of malondialdehyde in biological samples. J Chromatogr B 2002;775:121–6.

    Article  CAS  Google Scholar 

  26. Omaye ST, Turnbull JD, Sauberlich HE. Selected methods for the determination of ascorbic acid in animal cells, tissues, and fluids. Methods Enzymol 1979;62:3–11.

    Article  CAS  PubMed  Google Scholar 

  27. Flohe L. Superoxide dismutase assays. Methods Enzymol 1984;105:93–104.

    Article  CAS  PubMed  Google Scholar 

  28. Valipour P, Heidarian E, Khoshdel A, Gholami-Arjenaki M. Protective effects of hydroalcoholic extract of Ferulago angulata against gentamicin-induced nephrotoxicity in rats. Iran J Kidney Dis 2016; 10.

  29. Gabe M. Techniques histologiques. 6th ed. Paris: Masson Cie; 1968.

    Google Scholar 

  30. World Health Organization. Model list of essential medicines, 19th list. April.

  31. Feldman M, Friedman LS, Brandt LJ. Sleisenger and Fordtran’s gastrointestinal and liver disease. Philadelphia PA: Saunders Elsevier; 2010.

    Google Scholar 

  32. Feng L, Mao W, Zhang J, Liu X, Jiao Y, Zhao X, et al. Pharmacokinetic variations of tetramethylpyrazine phosphate after oral administration in hepatic precancerous mice and its hepatoprotective effects. Drug Dev Ind Pharm 2014;40:1–8.

    Article  CAS  PubMed  Google Scholar 

  33. Messarah M, Amamra W, Boumendjel A, Barkat L, Bouasla I, Abdennour C, et al. Ameliorating effects of curcumin and vitamin E on diazinon-induced oxidative damage in rat liver and erythrocytes. Toxicol Ind Health 2013;29:77–88.

    Article  CAS  PubMed  Google Scholar 

  34. Feng XM, Xiong J, Qin H, Liu W, Chen RN, Shang W, et al. Fluoxetine induces hepatic lipid accumulation via both promotion of the SREBP1c-related lipogenesis and reduction of lipolysis in primary mouse hepatocytes. CNS Neurosci Ther 2012;18:974–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Cheng D, Chu CH, Chen L, Feder JN, Mintier GA, Wu Y, et al. Expression, purification, and characterization of human and rat acetyl coenzyme A carboxylase (ACC) isozymes. Protein Expr Purif 2007;51(1):11–21.

    Article  CAS  PubMed  Google Scholar 

  36. Tung Y-T, Wu J-H, Huang C-C, Peng H-C, Chen Y-L, Yang S-C, et al. Protective effect of Acacia confusa bark extract and its active compound gallic acid against carbon tetrachloride-induced chronic liver injury in rats. Food Chem Toxicol 2009;47:1385–92.

    Article  CAS  PubMed  Google Scholar 

  37. Beal MF. Oxidatively modified proteins in aging and disease 1, 2. Free Radic Biol Med 2002;32:797–803.

    Article  CAS  PubMed  Google Scholar 

  38. Djordjevic J, Djordjevic A, Adzic M, Elaković I, Matić G, Radojcic MB. Fluoxetine affects antioxidant system and promotes apoptotic signaling in Wistar rat liver. Eur J Pharmacol 2011;659:61–6.

    Article  CAS  PubMed  Google Scholar 

  39. Park JC, Han WD, Park JR, Choi SH, Choi JW. Changes in hepatic drug metabolizing enzymes and lipid peroxidation by methanol extract and major compound of Orostachys japonicus. J Ethnopharmacol 2005;102:313–8.

    Article  CAS  PubMed  Google Scholar 

  40. Padayatty SJ, Katz A, Wang Y, Eck P, Kwon O, Lee J-H, et al. Vitamin C as an antioxidant: evaluation of its role in disease prevention. J Am Coll Nutr 2003;22:18–35.

    Article  CAS  PubMed  Google Scholar 

  41. El-Ashker M, Abdelhamid F, Risha E, Salama M, El-Sebaei M. Vitamin C ameliorates gentamicin-induced acute kidney injury in equines: an experimental study. J Equine Vet Sci 2015;35:238–43, doi:https://doi.org/10.1016/j.jevs.2015.01.004.

    Article  Google Scholar 

  42. Sahu BD, Tatireddy S, Koneru M, Borkar RM, Kumar JM, Kuncha M, et al. Naringin ameliorates gentamicin-induced nephrotoxicity and associated mitochondrial dysfunction, apoptosis and inflammation in rats: possible mechanism of nephroprotection. Toxicol Appl Pharmacol 2014;277:8–20.

    Article  CAS  PubMed  Google Scholar 

  43. Tracey KJ. The inflammatory reflex. Nature 2002;420:853–9.

    Article  CAS  PubMed  Google Scholar 

  44. Pan Y, Zhang W-Y, Xia X, Kong L-D. Effects of icariin on hypothalamic-pituitary-adrenal axis action and cytokine levels in stressed Sprague-Dawley rats. Biol Pharm Bull 2006;29:2399–403.

    Article  CAS  PubMed  Google Scholar 

  45. Ansari MA, Raish M, Ahmad A, Ahmad SF, Mudassar S, Mohsin K, et al. Sinapic acid mitigates gentamicin-induced nephrotoxicity and associated oxidative/nitrosative stress, apoptosis, and inflammation in rats. Life Sci 2016;165:1–8.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Esfandiar Heidarian.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Karimi-Khouzani, O., Heidarian, E. & Amini, S.A. Anti-inflammatory and ameliorative effects of gallic acid on fluoxetine-induced oxidative stress and liver damage in rats. Pharmacol. Rep 69, 830–835 (2017). https://doi.org/10.1016/j.pharep.2017.03.011

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1016/j.pharep.2017.03.011

Keywords

Navigation