Skip to main content
SpringerLink
Log in

Etoricoxib treatment prevented body weight gain and ameliorated oxidative stress in the liver of high-fat diet–fed rats

  • Original Article
  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Abstract

The main focus of this study was to determine the role of etoricoxib in counterbalancing the oxidative stress, metabolic disturbances, and inflammation in high-fat (HF) diet–induced obese rats. To conduct this study, 28 male Wistar rats (weighing 190–210 g) were distributed randomly into four groups: control, control + etoricoxib, HF, and HF + etoricoxib. After 8 weeks of treatment with etoricoxib (200 mg/kg), all the animals were sacrificed followed by the collection of blood and tissue samples in order to perform biochemical tests along with histological staining on hepatic tissues. According to this study, etoricoxib treatment prevented the body weight gain in HF diet–fed rats. Furthermore, rats of HF + etoricoxib group exhibited better blood glucose tolerance than the rats of HF diet–fed group. In addition, etoricoxib also markedly normalized HF diet–mediated rise of hepatic enzyme activity. Etoricoxib treatment lowered the level of oxidative stress indicators significantly with a parallel augmentation of antioxidant enzyme activities. Furthermore, etoricoxib administration helped in preventing inflammatory cell invasion, collagen accumulation, and fibrotic catastrophe in HF diet–fed rats. The findings of the present work are suggestive of the helpful role of etoricoxib in deterring the metabolic syndrome as well as other deleterious pathological changes afflicting the HF diet–fed rats.

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
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Abbreviations

AT:

adipose tissue

HF:

high-fat

COX:

cyclooxygenase

ROS:

reactive oxygen species

TNF-α:

tumor necrosis factor-alpha

LDL:

low-density lipoprotein

HDL:

high-density lipoprotein

MDA:

malondialdehyde

APOP:

advanced protein oxidation product

NO:

nitric oxide

ALT:

alanine aminotransferase

AST:

aspartate aminotransferase

ALP:

alkaline phosphatase

HF:

high fat

H2O2 :

hydrogen peroxide

SOD:

superoxide dismutase

CAT:

catalase

MPO:

myeloperoxidase

References

  • Alkhouri N, Dixon LJ, Feldstein AE (2009) Lipotoxicity in nonalcoholic fatty liver disease: not all lipids are created equal. Expert Rev Gastroenterol Hepatol 3:445–451. https://doi.org/10.1586/egh.09.32

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Arriazu E, Ruiz de Galarreta M, Cubero FJ, Varela-Rey M, Pérez de Obanos MP, Leung TM, Lopategi A, Benedicto A, Abraham-Enachescu I, Nieto N (2014) Extracellular matrix and liver disease. Antioxid Redox Signal 21:1078–1097. https://doi.org/10.1089/ars.2013.5697

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bäck M, Yin L, Ingelsson E (2011) Cyclooxygenase-2 inhibitors and cardiovascular risk in a nation-wide cohort study after the withdrawal of rofecoxib. Eur Heart J 33:1928–1933. https://doi.org/10.1093/eurheartj/ehr421

    Article  CAS  PubMed  Google Scholar 

  • Bagi Z, Erdei N, Papp Z, Édes I, Koller A (2006) Up-regulation of vascular cyclooxygenase-2 in diabetes mellitus. Pharmacol Rep 58:52

    PubMed  Google Scholar 

  • Bais S, Singh GS, Sharma R (2014) Antiobesity and hypolipidemic activity of Moringa oleifera leaves against high fat diet-induced obesity in rats. Adv Biol 2014:162914

    Article  Google Scholar 

  • Bolduc C, Larose M, Lafond N, Yoshioka M, Rodrigue M-A, Morissette J, Labrie C, Raymond V, St-Amand J (2004) Adipose tissue transcriptome by serial analysis of gene expression. Obes Res 12:750–757. https://doi.org/10.1038/oby.2004.90

    Article  CAS  PubMed  Google Scholar 

  • Burhans MS, Hagman DK, Kuzma JN, Schmidt KA, Kratz M (2018) Contribution of adipose tissue inflammation to the development of type 2 diabetes mellitus. Compr Physiol 9:1–58. https://doi.org/10.1002/cphy.c170040

    Article  PubMed  PubMed Central  Google Scholar 

  • Cannon CP, Curtis SP, FitzGerald GA, Krum H, Kaur A, Bolognese JA, Reicin AS, Bombardier C, Weinblatt ME, van der Heijde D, Erdmann E, Laine L (2006) Cardiovascular outcomes with etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomised comparison. Lancet 368:1771–1781

    Article  CAS  Google Scholar 

  • Chávez E, Segovia J, Shibayama M, Tsutsumi V, Vergara P, Castro-Sánchez L, Salazar EP, Moreno MG, Muriel P (2010) Antifibrotic and fibrolytic properties of celecoxib in liver damage induced by carbon tetrachloride in the rat. Liver Int 30:969–978. https://doi.org/10.1111/j.1478-3231.2010.02256.x

    Article  CAS  PubMed  Google Scholar 

  • Chávez E, Castro-Sánchez L, Shibayama M, Tsutsumi V, Pérez Salazar E, Moreno MG, Muriel P (2012) Effects of acetyl salicylic acid and ibuprofen in chronic liver damage induced by CCl4. J Appl Toxicol 32:51–59. https://doi.org/10.1002/jat.1638

    Article  CAS  PubMed  Google Scholar 

  • Choi Y, Abdelmegeed MA, Song B-J (2016) Preventive effects of dietary walnuts on high-fat-induced hepatic fat accumulation, oxidative stress and apoptosis in mice. J Nutr Biochem 38:70–80. https://doi.org/10.1016/j.jnutbio.2016.08.013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chooi YC, Ding C, Magkos F (2019) The epidemiology of obesity. Metabolism 92:6–10

    Article  CAS  Google Scholar 

  • Ekor M, Odewabi AO, Kale OE, Adesanoye OA, Bamidele TO (2013) Celecoxib, a selective cyclooxygenase-2 inhibitor, lowers plasma cholesterol and attenuates hepatic lipid peroxidation during carbon-tetrachloride–associated hepatotoxicity in rats. Drug Chem Toxicol 36:1–8. https://doi.org/10.3109/01480545.2011.642380

    Article  CAS  PubMed  Google Scholar 

  • Faghihimani E, Aminorroaya A, Rezvanian H, Adibi P, Ismail-Beigi F, Amini M (2013) Salsalate improves glycemic control in patients with newly diagnosed type 2 diabetes. Acta Diabetol 50:537–543. https://doi.org/10.1007/s00592-011-0329-2

    Article  CAS  PubMed  Google Scholar 

  • Ferrante AW Jr (2013) The immune cells in adipose tissue. Diabetes Obes Metab 15(Suppl 3):34–38. https://doi.org/10.1111/dom.12154

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guilherme A, Virbasius JV, Puri V, Czech MP (2008) Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Nat Rev Mol Cell Biol 9:367–377

    Article  CAS  Google Scholar 

  • Hawley SA, Fullerton MD, Ross FA, Schertzer JD, Chevtzoff C, Walker KJ, Peggie MW, Zibrova D, Green KA, Mustard KJ, Kemp BE, Sakamoto K, Steinberg GR, Hardie DG (2012) The ancient drug salicylate directly activates AMP-activated protein kinase. Science 336:918–922. https://doi.org/10.1126/science.1215327

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hermann M, Camici G, Fratton A, Hurlimann D, Tanner FC, Hellermann JP, Fiedler M, Thiery J, Neidhart M, Gay RE, Gay S, Lüscher TF, Ruschitzka F (2003) Differential effects of selective cyclooxygenase-2 inhibitors on endothelial function in salt-induced hypertension. Circulation 108:2308–2311

    Article  CAS  Google Scholar 

  • Hsieh P-S (2011) Obesity-induced adipose tissue inflammation and insulin resistance: role of the adipocyte in development of type 2 diabetes. In: Croniger C (ed). IntechOpen, https://doi.org/10.5772/20561.

  • Hsieh P-S, Jin J-S, Chiang C-F, Chan P-C, Chen C-H, Shih K-C (2009) COX-2-mediated inflammation in fat is crucial for obesity-linked insulin resistance and fatty liver. Obesity 17:1150–1157. https://doi.org/10.1038/oby.2008.674

    Article  CAS  PubMed  Google Scholar 

  • Hu YP, Peng YB, Zhang YF, Wang Y, Yu WR, Yao M, Fu XJ (2017) Reactive oxygen species mediated prostaglandin E2 contributes to acute response of epithelial injury. Oxidative Med Cell Longev 2017:4123854–4123858. https://doi.org/10.1155/2017/4123854

    Article  CAS  Google Scholar 

  • Hung C-S, Lee JK, Yang CY, Hsieh HR, Ma WY, Lin MS, Liu PH, Shih SR, Liou JM, Chuang LM, Chen MF, Lin JW, Wei JN, Li HY (2014) Measurement of visceral fat: should we include retroperitoneal fat? PLoS One 9:e112355. https://doi.org/10.1371/journal.pone.0112355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hurt RT, Kulisek C, Buchanan LA, McClave SA (2010) The obesity epidemic: challenges, health initiatives, and implications for gastroenterologists. Gastroenterol Hepatol 6:780

    Google Scholar 

  • Kendig EL, Schneider SN, Clegg DJ, Genter MB, Shertzer HG (2008) Over-the-counter analgesics normalize blood glucose and body composition in mice fed a high fat diet. Biochem Pharmacol 76:216–224. https://doi.org/10.1016/j.bcp.2008.05.001

    Article  CAS  PubMed  Google Scholar 

  • Khan RA (2012) Protective effects of Sonchus asper (L.) Hill,(Asteraceae) against CCl4-induced oxidative stress in the thyroid tissue of rats. BMC Complement Altern Med 12:181

    Article  Google Scholar 

  • Lasker S, Rahman MM, Parvez F, Zamila M, Miah P, Nahar K, Kabir F, Sharmin SB, Subhan N, Ahsan GU, Alam MA (2019) High-fat diet-induced metabolic syndrome and oxidative stress in obese rats are ameliorated by yogurt supplementation. Sci Rep 9:20026. https://doi.org/10.1038/s41598-019-56538-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Libby P, Ridker PM, Maseri A (2002) Inflammation and atherosclerosis. Circulation 105:1135–1143

    Article  CAS  Google Scholar 

  • Liu T-T, Shih K-C, Kao C-C, Cheng W-T, Hsieh P-S (2009) Importance of cyclooxygenase 2-mediated low-grade inflammation in the development of fructose-induced insulin resistance in rats. Chin J Phys 52:65–71

    CAS  Google Scholar 

  • Matsumoto AK, Melian A, Mandel DR, McIlwain H, Borenstein D, Zhao PL, Lines CR, Gertz BJ, Curtis S, Etoricoxib Rheumatoid Arthritis Study Group (2002) A randomized, controlled, clinical trial of etoricoxib in the treatment of rheumatoid arthritis. J Rheumatol 29:1623–1630

    CAS  PubMed  Google Scholar 

  • McAdam BF, Catella-Lawson F, Mardini IA, Kapoor S, Lawson JA, FitzGerald GA (1999) Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: the human pharmacology of a selective inhibitor of COX-2. Proc Natl Acad Sci U S A 96:272–277

    Article  CAS  Google Scholar 

  • Mells JE, Fu PP, Kumar P, Smith T, Karpen SJ, Anania FA (2015) Saturated fat and cholesterol are critical to inducing murine metabolic syndrome with robust nonalcoholic steatohepatitis. J Nutr Biochem 26:285–292. https://doi.org/10.1016/j.jnutbio.2014.11.002

    Article  CAS  PubMed  Google Scholar 

  • Misra HP, Fridovich I (1972) The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 247:3170–3175

    CAS  PubMed  Google Scholar 

  • Moraes BM, do Amaral BC, Morimoto M, Vieira LC, Perazzo FF, Carvalho JT (2007) Anti-inflammatory and analgesic actions of etoricoxib (an NSAID) combined with misoprostol. Inflammopharmacol 15:175–178

    Article  CAS  Google Scholar 

  • Mraz M, Haluzik M (2014) The role of adipose tissue immune cells in obesity and low-grade inflammation. J Endocrinol 222:R113–R127

    Article  CAS  Google Scholar 

  • Must A, Anderson S (2006) Body mass index in children and adolescents: considerations for population-based applications. Int J Obes 30:590–594

    Article  CAS  Google Scholar 

  • Nie L, Yuan XL, Jiang KT, Jiang YH, Yuan J, Luo L, Cui SW, Sun C (2017) Salsalate activates skeletal muscle thermogenesis and protects mice from high-fat diet induced metabolic dysfunction. EBioMedicine 23:136–145. https://doi.org/10.1016/j.ebiom.2017.08.004

    Article  PubMed  PubMed Central  Google Scholar 

  • Niehaus W Jr, Samuelsson B (1968) Formation of malonaldehyde from phospholipid arachidonate during microsomal lipid peroxidation. Eur J Biochem 6:126–130

    Article  CAS  Google Scholar 

  • Organization WH (2016) World Health Organization obesity and overweight fact sheet.

  • Panchal SK, Poudyal H, Iyer A, Nazer R, Alam A, Diwan V, Kauter K, Sernia C, Campbell F, Ward L, Gobe G, Fenning A, Brown L (2011) High-carbohydrate high-fat diet–induced metabolic syndrome and cardiovascular remodeling in rats. J Cardiovasc Pharmacol 57:51–64

    Article  CAS  Google Scholar 

  • Pitt B, Pepine C, Willerson JT (2002) Cyclooxygenase-2 inhibition and cardiovascular events. Circulation. 106:167–169

    Article  Google Scholar 

  • Pontsler AV, Hilaire AS, Marathe GK, Zimmerman GA, McIntyre TM (2002) Cyclooxygenase-2 is induced in monocytes by peroxisome proliferator activated receptor γ and oxidized alkyl phospholipids from oxidized low density lipoprotein. J Biol Chem 277:13029–13036

    Article  CAS  Google Scholar 

  • Rahman MM, Alam MN, Ulla A, Sumi FA, Subhan N, Khan T, Sikder B, Hossain H, Reza HM, Alam MA (2017) Cardamom powder supplementation prevents obesity, improves glucose intolerance, inflammation and oxidative stress in liver of high carbohydrate high fat diet induced obese rats. Lipids Health Dis 16:151

    Article  Google Scholar 

  • Rosin O (2008) The economic causes of obesity: a survey. J Econ Surv 22:617–647

    Article  Google Scholar 

  • Rytka JM, Wueest S, Schoenle EJ, Konrad D (2011) The portal theory supported by venous drainage-selective fat transplantation. Diabetes 60:56–63. https://doi.org/10.2337/db10-0697

    Article  CAS  PubMed  Google Scholar 

  • Schmidt MI, Duncan BB (2003) Diabesity: an inflammatory metabolic condition. Clin Chem Lab Med 41:1120–1130

    Article  CAS  Google Scholar 

  • Shikora SA (2005) Severe obesity: a growing health concern ASPEN should not ignore. J Parenter Enter Nutr 29:288–297

    Article  Google Scholar 

  • Smith BK, Ford RJ, Desjardins EM, Green AE, Hughes MC, Houde VP, Day EA, Marcinko K, Crane JD, Mottillo EP, Perry CGR, Kemp BE, Tarnopolsky MA, Steinberg GR (2016) Salsalate (salicylate) uncouples mitochondria, improves glucose homeostasis, and reduces liver lipids independent of AMPK-β1. Diabetes 65:3352–3361. https://doi.org/10.2337/db16-0564

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Surwit RS, Kuhn CM, Cochrane C, McCubbin JA, Feinglos MN (1988) Diet-induced type II diabetes in C57BL/6 J mice. Diabetes 37:1163–1167

    Article  CAS  Google Scholar 

  • Tiwari BK, Kumar D, Abidi A, Rizvi SI (2014) Efficacy of composite extract from leaves and fruits of medicinal plants used in traditional diabetic therapy against oxidative stress in alloxan-induced diabetic rats. ISRN Pharmacol 2014

  • Tracey WR, Tse J, Carter G (1995) Lipopolysaccharide-induced changes in plasma nitrite and nitrate concentrations in rats and mice: pharmacological evaluation of nitric oxide synthase inhibitors. J Pharmacol Exp Ther 272:1011–1015

    CAS  PubMed  Google Scholar 

  • Ulla A, Alam MA, Sikder B, Sumi FA, Rahman MM, Habib ZF, Mohammed MK, Subhan N, Hossain H, Reza HM (2017) Supplementation of Syzygium cumini seed powder prevented obesity, glucose intolerance, hyperlipidemia and oxidative stress in high carbohydrate high fat diet induced obese rats. BMC Complement Altern Med 17:289

    Article  Google Scholar 

  • White S et al (2013) Modelo de obesidade induzida por dieta hiperlipidica e associada à resistência à ação da insulina e intolerância a glicose. Arq Bras Endocrinol Metab 57:339–345

    Article  Google Scholar 

  • Witko-Sarsat V, Friedlander M, Capeillère-Blandin C, Nguyen-Khoa T, Nguyen AT, Zingraff J, Jungers P, Descamps-Latscha B (1996) Advanced oxidation protein products as a novel marker of oxidative stress in uremia. Kidney Int 49:1304–1313

    Article  CAS  Google Scholar 

  • Yan H, Kermouni A, Abdel-Hafez M, Lau DC (2003) Role of cyclooxygenases COX-1 and COX-2 in modulating adipogenesis in 3T3-L1 cells. J Lipid Res 44:424–429. https://doi.org/10.1194/jlr.M200357-JLR200

    Article  CAS  PubMed  Google Scholar 

  • Yang J, Fernández-Galilea M, Martínez-Fernández L, González-Muniesa P, Pérez-Chávez A, Martínez JA, Moreno-Aliaga MJ (2019) Oxidative stress and non-alcoholic fatty liver disease: effects of omega-3 fatty acid supplementation. Nutrients 11:872

    Article  CAS  Google Scholar 

  • Yu J, Ip E, dela Peña A, Hou JY, Sesha J, Pera N, Hall P, Kirsch R, Leclercq I, Farrell GC (2006) COX-2 induction in mice with experimental nutritional steatohepatitis: role as pro-inflammatory mediator. Hepatol 43:826–836. https://doi.org/10.1002/hep.21108

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors appreciate all the supports provided by the Department of Pharmaceutical Sciences, North South University, Bangladesh, where the research work was conducted.

Availability of data and material

Backup of all data generated in this study are stored in both laboratory and authors’ computer which will be available upon request.

Author information

Author notes

  1. Fariha Kabir and Kamrun Nahar contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, North South University, Dhaka, 1219, Bangladesh

    Fariha Kabir, Kamrun Nahar, Md. Mizanur Rahman, Fariha Mamun, Shoumen Lasker, Ferdous Khan, Tahmina Yasmin, Khondker Ayesha Akter, Nusrat Subhan & Md. Ashraful Alam

Authors
  1. Fariha Kabir
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kamrun Nahar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Md. Mizanur Rahman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fariha Mamun
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shoumen Lasker
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ferdous Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tahmina Yasmin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Khondker Ayesha Akter
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Nusrat Subhan
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Md. Ashraful Alam
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

MAA, KAA, and NS developed the core study concept and design, coordinated the whole study, and trained and supervised FK, TY, KN, MMR, SL, and FM in all activities relevant to this study. FK, KN, and SL conducted animal handling and experiment as well as sacrificing followed by their tissue and blood collection. Biochemical and histological assessments were performed by FK, KN, SL, TY, and MMR. MMR, KAA, and MAA carried out the statistical analysis of this study as well. FK, MAA, KAA, and FM formulated the final content of this research paper that was read and approved by all authors. The authors also declare that all data were generated in-house and that no paper mill was used.

Corresponding author

Correspondence to Md. Ashraful Alam.

Ethics declarations

Competing interest

The authors declare that they have no competing interests.

Ethics approval

The Institutional Animal Research Ethical Committee approved the experimental protocol.

Consent for publication

The final content of this paper was read and approved by all authors for publication.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(XLSX 54 kb).

ESM 2

(XLSX 16 kb).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kabir, F., Nahar, K., Rahman, M.M. et al. Etoricoxib treatment prevented body weight gain and ameliorated oxidative stress in the liver of high-fat diet–fed rats. Naunyn-Schmiedeberg's Arch Pharmacol 394, 33–47 (2021). https://doi.org/10.1007/s00210-020-01960-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00210-020-01960-9

Keywords

Search

Navigation