INFLUENCE OF PARACETAMOL AND CELECOXIB ON LIVER FUNCTION AND PROOXIDANT-ANTIOXIDANT BALANCE IN RATS UNDER ACUTE HEAT STRESS
DOI:
https://doi.org/10.11603/2312-0967.2025.2.15393Keywords:
acute heat stress, paracetamol, celecoxib, liver, oxidative stress, ATPAbstract
The aim of the work – to determine the effects of celecoxib and paracetamol on liver function and oxidative stress levels in rats under a model of acute heat stress.
Materials and Methods. The experiment was conducted on male white rats. Acute heat stress was modeled by 30-minute exposure at +55 °C. Rectal temperature, biochemical markers of liver function in blood serum, adenosine triphosphate (ATP) content, indicators of lipid peroxidation (LPO) and antioxidant system (AOS) in the liver, and liver mass coefficient were evaluated. Paracetamol and celecoxib were administered once, 60 minutes prior to heat exposure.
Results and Discussion. Animals with the control pathology exhibited hyperthermia, hyperproteinemia due to hemoconcentration caused by dehydration, reduced serum gamma-glutamyltransferase activity, decreased levels of reduced glutathione, accumulation of LPO products, and decreased ATP content in the liver. Celecoxib significantly reduced temperature, completely eliminated hyperproteinemia, normalized gamma-glutamyltransferase activity and LPO/AOS parameters, and increased ATP levels. Paracetamol also reduced hyperthermia but did not fully eliminate hyperproteinemia, worsened the prooxidant-antioxidant balance, and left minimal energy supply to the liver.
Conclusions. Celecoxib demonstrates hepatoprotective properties under acute heat stress, reduces oxidative stress, and supports energy metabolism. Paracetamol, despite its antihyperthermic effect, does not provide a comparable level of liver protection.
References
Gauer R, Meyers BK. Heat-Related Illnesses. Am Fam Physician. 2019 Apr 15;99(8):482-489.
Bauman J, Spano S, Storkan M. Heat-Related Illnesses. Emerg Med Clin North Am. 2024 Aug;42(3):485-492. doi: 10.1016/j.emc.2024.02.010. DOI: https://doi.org/10.1016/j.emc.2024.02.010
Garcia CK, Renteria LI, Leite-Santos G, Leon LR, Laitano O. Exertional heat stroke: pathophysiology and risk factors. BMJ Med. 2022;1(1):e000239. doi:10.1136/bmjmed-2022-000239. DOI: https://doi.org/10.1136/bmjmed-2022-000239
Ebi KL, Capon A, Berry P, Broderick C, de Dear R, Havenith G, Honda Y, Kovats RS, Ma W, Malik A, Morris NB, Nybo L, Seneviratne SI, Vanos J, Jay O. Hot weather and heat extremes: health risks. Lancet. 2021 Aug 21;398(10301):698-708. doi: 10.1016/S0140-6736(21)01208-3. DOI: https://doi.org/10.1016/S0140-6736(21)01208-3
Cramer MN, Gagnon D, Laitano O, Crandall CG. Human temperature regulation under heat stress in health, disease, and injury. Physiol Rev. 2022;102(4):1907-1989. doi:10.1152/physrev.00047.2021. DOI: https://doi.org/10.1152/physrev.00047.2021
Yang X, Wang H, Shen C, Dong X, Li J, Liu J. Effects of isorhamnetin on liver injury in heat stroke-affected rats under dry-heat environments via oxidative stress and inflammatory response. Sci Rep. 2024 Mar 29;14(1):7476. doi: 10.1038/s41598-024-57852-y. DOI: https://doi.org/10.1038/s41598-024-57852-y
Wang F, Zhang Y, Li J, Xia H, Zhang D, Yao S. The pathogenesis and therapeutic strategies of heat stroke-induced liver injury. Crit Care. 2022 Dec 17;26(1):391. doi: 10.1186/s13054-022-04273-w. DOI: https://doi.org/10.1186/s13054-022-04273-w
Chen Y, Yu T. Mouse liver is more resistant than skeletal muscle to heat-induced apoptosis. Cell Stress Chaperones. 2021 Jan;26(1):275-281. doi: 10.1007/s12192-020-01163-4. DOI: https://doi.org/10.1007/s12192-020-01163-4
Knapik JJ, Epstein Y. Exertional heat stroke: pathophysiology, epidemiology, diagnosis, treatment, and prevention. J Spec Oper Med. 2019;19(2):108-116. doi:10.55460/5P2Q-1MBQ. DOI: https://doi.org/10.55460/5P2Q-1MBQ
Chuykova P, Shtrygol' S, Taran A, Yudkevych T, Lebedinets I, Oklei D. Acute heat trauma model in rats, gender-dependent thermoresistance, and screening of potential thermoprotectors. ScienceRise: Pharm Sci. 2024;2(48):4-11. doi:10.15587/2519-4852.2024.301620 DOI: https://doi.org/10.15587/2519-4852.2024.301620
Pidruchna SR, Benedyct VV, Piatnochka VI, Melnyk NA, Zakharchuk UM. Changes of pro- and antioxidant indicators in experimental animals under acute small bowel obstructions. J Med Life. 2021 Jan-Mar;14(1):32-36. doi: 10.25122/jml-2020-0066. DOI: https://doi.org/10.25122/jml-2020-0066
Izhytska NV, Sushko YI, Hudyma AA, Zachepa OA, Antonyshyn IV, Denefil OV. The effect of cell therapy on the intensity of lipid peroxidation processes in the liver, kidneys and lungs of rats of different ages under conditions of experimental cranio-skeletal trauma. Wiad Lek. 2024;77(11):2127-2134. doi: 10.36740/WLek/197081. DOI: https://doi.org/10.36740/WLek/197081
Zhang J, Chen R, Yu Z, Xue L. Superoxide Dismutase (SOD) and Catalase (CAT) Activity Assay Protocols for Caenorhabditis elegans. Bio Protoc. 2017 Aug 20;7(16):e2505. doi: 10.21769/BioProtoc.2505. DOI: https://doi.org/10.21769/BioProtoc.2505
Hadwan MH. New method for assessment of serum catalase activity. Indian J Sci Technol. 2016;9(4). doi:10.17485/ijst/2016/v9i4/78537. DOI: https://doi.org/10.17485/ijst/2016/v9i4/80499
Xu L, Yu Y, Sang R, Li J, Ge B, Zhang X. Protective Effects of Taraxasterol against Ethanol-Induced Liver Injury by Regulating CYP2E1/Nrf2/HO-1 and NF-κB Signaling Pathways in Mice. Oxid Med Cell Longev. 2018 Sep 23;2018:8284107. doi: 10.1155/2018/8284107. DOI: https://doi.org/10.1155/2018/8284107
Zhang G, Yang W, Zou P, Jiang F, Zeng Y, Chen Q, Sun L, Yang H, Zhou N, Wang X, Liu J, Cao J, Zhou Z, Ao L. Mitochondrial functionality modifies human sperm acrosin activity, acrosome reaction capability and chromatin integrity. Hum Reprod. 2019 Jan 1;34(1):3-11. doi: 10.1093/humrep/dey335. DOI: https://doi.org/10.1093/humrep/dey335
Trefts E, Gannon M, Wasserman DH. The liver. Curr Biol. 2017 Nov 6;27(21):R1147-R1151. doi: 10.1016/j.cub.2017.09.019. DOI: https://doi.org/10.1016/j.cub.2017.09.019
Koner BC, Banerjee BD, Ray A. Effects of stress on gamma glutamyl transpeptidase (GGT) activity in lymphoid system of rats: modulation by drugs. Indian J Exp Biol. 1997 Mar;35(3):222-4.
Vázquez-Meza H, Vilchis-Landeros MM, Vázquez-Carrada M, Uribe-Ramírez D, Matuz-Mares D. Cellular Compartmentalization, Glutathione Transport and Its Relevance in Some Pathologies. Antioxidants (Basel). 2023 Mar 29;12(4):834. doi: 10.3390/antiox12040834. DOI: https://doi.org/10.3390/antiox12040834
Pomacu MM, Stănciulescu CE, Trașcă DM, Pădureanu V, Goga LD, Pisoschi CG, Bugă AM. Relationship between Serum Gamma-Glutamyltransferase and Glutathione Antioxidant System in Patients with Liver Cirrhosis of Various Etiology. Curr Health Sci J. 2022 Oct-Dec;48(4):436-445. doi: 10.12865/CHSJ.48.04.11.
Singh A, Kukreti R, Saso L, Kukreti S. Oxidative Stress: A Key Modulator in Neurodegenerative Diseases. Molecules. 2019 Apr 22;24(8):1583. doi: 10.3390/molecules24081583. DOI: https://doi.org/10.3390/molecules24081583
Chidiac AS, Buckley NA, Noghrehchi F, Cairns R. Paracetamol (acetaminophen) overdose and hepatotoxicity: mechanism, treatment, prevention measures, and estimates of burden of disease. Expert Opin Drug Metab Toxicol. 2023 Jan-Jun;19(5):297-317. doi: 10.1080/17425255.2023.2223959. DOI: https://doi.org/10.1080/17425255.2023.2223959
Hinson JA, Roberts DW, James LP. Mechanisms of acetaminophen-induced liver necrosis. Handb Exp Pharmacol. 2010;(196):369-405. doi: 10.1007/978-3-642-00663-0_12. DOI: https://doi.org/10.1007/978-3-642-00663-0_12
Tai Y, Zhao C, Zhang L, Tang S, Jia X, Tong H, Liu R, Tang C, Gao J. Celecoxib reduces hepatic vascular resistance in portal hypertension by amelioration of endothelial oxidative stress. J Cell Mol Med. 2021 Nov;25(22):10389-10402. doi: 10.1111/jcmm.16968. DOI: https://doi.org/10.1111/jcmm.16968
Deng C, Lu C, Wang K, Chang M, Shen Y, Yang X, Sun H, Yao X, Qiu C, Xu F. Celecoxib ameliorates diabetic sarcopenia by inhibiting inflammation, stress response, mitochondrial dysfunction, and subsequent activation of the protein degradation systems. Front Pharmacol. 2024 Jan 19;15:1344276. doi: 10.3389/fphar.2024.1344276. DOI: https://doi.org/10.3389/fphar.2024.1344276
Chuykova P, Shtrygol S. Effect of celecoxib and paracetamol on the functional state of the central nervous system, pain sensitivity, and physical endurance in rats with acute heat injury. Medicni perspektivi. 2024;29(3):11–19. doi:10.26641/2307-0404.2024.3.313072. DOI: https://doi.org/10.26641/2307-0404.2024.3.313072
Chuikova PO, Shtrygol SY, Lebedinets IO, Lytkin DV. Effect of paracetamol and celecoxib on the state of hemocoagulation in the most acute period of heat injury in rats. Medicni perspektivi. 2025;30(1):22–8. doi:10.26641/2307-0404.2025.1.325234. DOI: https://doi.org/10.26641/2307-0404.2025.1.325234
Chuykova PO, Shtrygol SY. Comparative efficacy of celecoxib and paracetamol as thermoprotective agents in an acute heat injury model. In: Contemporary Pharmacy: Issues, Challenges and Expectations. Abstracts of the international scientific-practical conference; 2025 Apr 10; Kaunas, Lithuania. 2025. p. 83.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Pharmaceutical Review / Farmacevtičnij časopis
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
The authors who publish their materials in this journal agree with the following terms:
- Authors reserve the right to authorship of their work and assign to the journal the right to first publish this work under the terms of the Creative Commons Attribution License, which allows other persons to freely distribute the published work with a mandatory reference to the authors of original work and the first publication of work in this journal
. - Authors have the right to make independent extra-exclusive work agreements in the form they are published by this journal (for example, posting work in an electronic repository of an institution or publishing as part of a monograph), provided that the link to the first publication of the work in this journal is maintained.
Journal policy allows and encourages publication of manuscripts on the Internet (for example, in institutions repositories or on personal websites), both before the publication of this manuscript and during its editorial review, as it contributes to productive scientific discussion and positively affects the efficiency and dynamics of the citation of the published work (see The Effect of Open Access).
