Effect of celecoxib and paracetamol on the functional state of the central nervous system, pain sensitivity, and physical endurance of rats with acute heat injury

P.O. Chuikova; S.Yu. Shtrygol’

doi:10.26641/2307-0404.2024.3.313072

Authors

P.O. Chuikova National University of Pharmacy, Hryhoriia Skovorody str., 53, Kharkiv, 61002, Ukraine https://orcid.org/0000-0002-9622-1566
S.Yu. Shtrygol’ National University of Pharmacy, Hryhoriia Skovorody str., 53, Kharkiv, 61002, Ukraine https://orcid.org/0000-0001-7257-9048

DOI:

https://doi.org/10.26641/2307-0404.2024.3.313072

Keywords:

acute heat injury, cyclooxygenase inhibitors, celecoxib, paracetamol, central nervous system, pain sensitivity, physical endurance

Abstract

Acute heat injury (AHI) is a serious condition caused by an excessive increase in body temperature, usually due to prolonged exposure to high environmental temperatures or intense physical activity in the heat. Without timely treatment, heat stroke can lead to severe damage to the central nervous system with cerebral edema, profound disturbances in the water-salt balance and internal organs, coma and death. Since the effectiveness of drugs for the treatment of thermal injuries has not been proven, the search for new thermoprotective agents with different mechanisms of action, in particular inhibitors of the arachidonic acid cascade, is urgent. In a preliminary screening study on the AHI model in rats, it was found that among cyclooxygenase (COX) inhibitors, the highly selective COX-2 inhibitor celecoxib and the analgesic-antipyretic paracetamol are the most effective in preventing hyperthermia and improving the course of the recovery period. The purpose of this study was to determine the impact of the specified screening leaders on the functional state of the central nervous system, pain sensitivity and physical endurance in the recovery period of heat injury. The AHI model was reproduced on adult white male rats according to the previously proposed and validated method by means of a 30-minute exposure at +55°C. Animals were divided into 4 groups with 8 rats in each group: intact control, control pathology, paracetamol group and celecoxib group. Based on the results of the study, it was established that celecoxib exhibits a pronounced thermoprotective effect, probably improves the state of the central nervous system in terms of behavioral reactions and physical endurance of animals in the recovery period after acute heat injury. At the same time, paracetamol after acute heat injury does not have a distinct positive effect on the functional state of the central nervous system, moderately improves the physical endurance of rats and is inferior to celecoxib in all the studied parameters. These results open new opportunities for the development of approaches to the treatment of AHI and confirm the different effectiveness of the use of celecoxib and paracetamol in thermal injuries.

References

Garcia CK, Renteria LI, Leite-Santos G, Leon LR, Laitano O. Exertional heat stroke: pathophysiology and risk factors. BMJ Med. 2022 Oct 11;1(1):e000239. doi: https://doi.org/10.1136/bmjmed-2022-000239

Stillman JH. Heat Waves, the New Normal: Summertime Temperature Extremes Will Impact Animals, Ecosystems, and Human Communities. Physiology (Bethesda). 2019 Mar 1;34(2):86-100. doi: https://doi.org/10.1152/physiol.00040.2018

Périard JD, DeGroot D, Jay O. Exertional heat stroke in sport and the military: epidemiology and mitigation. Exp Physiol. 2022 Oct;107(10):1111-21. doi: https://doi.org/10.1113/EP090686

Kiatkitroj K, Arphorn S, Tangtong C, Maruo SJ, Ishimaru T. Risk factors associated with heat-related illness among sugarcane farmers in Thailand. Ind Health. 2022 Oct 1;60(5):447-58. doi: https://doi.org/10.2486/indhealth.2021-0161

How V, Singh S, Dang T, Fang Lee L, Guo HR. The effects of heat exposure on tropical farm workers in Malaysia: six-month physiological health monitoring. Int J Environ Health Res. 2023 Apr;33(4):413-29. doi: https://doi.org/10.1080/09603123.2022.2033706

Alari A, Letellier N, Benmarhnia T. Effect of different heat wave timing on cardiovascular and respiratory mortality in France. Sci Total Environ. 2023 Sep 20;892:164543. doi: https://doi.org/10.1016/j.scitotenv.2023.164543

Bauman J, Spano S, Storkan M. Heat-Related Illnesses. Emerg Med Clin North Am. 2024 Aug;42(3):485-92. doi: https://doi.org/10.1016/j.emc.2024.02.010

Knapik JJ, Epstein Y. Exertional Heat Stroke: Pathophysiology, Epidemiology, Diagnosis, Treatment, and Prevention. J Spec Oper Med. 2019 Summer;19(2):108-16. doi: https://doi.org/10.55460/5P2Q-1MBQ

Sorensen C, Hess J. Treatment and Prevention of Heat-Related Illness. N Engl J Med. 2022;387(15):1404-13. doi: https://doi.org/10.1056/NEJMcp2210623

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: Pharmaceutical Science. 2024 Apr;2(48):4-11. doi: https://doi.org/10.15587/2519-4852.2024.301620

Hock FJ, editor. Drug Discovery and Evaluation: Pharmacological Assays. B.: Springer Berlin Heidelberg; 2014. 2071 р.

Koval A, Shtrygol' S. 1-(5-Aetyl-3-methyl-6-phe-nyl-5h-[1,2,4]triazolo [3,4-b][1,3,4]thiadiazin-7-yl)-etha-none: dose-dependence of analgesic effect, lack of opioidergic mechanism of action, effect on behavioral reactionsand acute toxicity. Acta Medica Leopoliensia. 2023;29(3-4):192-203. doi: https://doi.org/10.25040/aml2023.3-4.192

Bonm AV, Elezgarai I, Gremel CM, Viray K, Bamford NS, Palmiter RD, et al. Control of exploration, motor coordination and amphetamine sensitization by cannabinoid CB1 receptors expressed in medium spiny neurons. Eur J Neurosci. 2021 Aug;54(3):4934-52. doi: https://doi.org/10.1111/ejn.15381

Karna SR, Kongara K, Singh PM, Chambers P, Lopez-Villalobos N. Evaluation of analgesic interaction between morphine, dexmedetomidine and maropitant using hot-plate and tailflick tests in rats. Vet Anaesth Analg. 2019 Jul;46(4):476-82. doi: https://doi.org/10.1016/j.vaa.2018.12.009

Armario A. The forced swim test: Historical, conceptual and methodological considerations and its relationship with individual behavioral traits. Neurosci Biobehav Rev. 2021 Sep;128:74-86. doi: https://doi.org/10.1016/j.neubiorev.2021.06.014

Habibzadeh F. Data Distribution: Normal or Abnormal? Journal of Korean medical science. 2024 Jan 22;39(3):e35. doi: https://doi.org/10.3346/jkms.2024.39.e35

Zhang Z, Wu X, Zou Z, Shen M, Liu Q, Zhangsun Z, et al. Heat stroke: Pathogenesis, diagnosis, and current treatment. Ageing Res Rev. 2024 Jul 8;100:102409. doi: https://doi.org/10.1016/j.arr.2024.102409

Phillis JW, Horrocks LA, Farooqui AA. Cyclooxygenases, lipoxygenases, and epoxygenases in CNS: their role and involvement in neurological disorders. Brain Res Rev. 2006 Sep;52(2):201-43. doi: https://doi.org/10.1016/j.brainresrev.2006.02.002

Calderwood SK, Bornstein B, Farnum EK, Stevenson MA. Heat shock stimulates the release of arachidonic acid and the synthesis of prostaglandins and leukotriene B4 in mammalian cells. J Cell Physiol. 1989 Nov;141(2):325-33. doi: https://doi.org/10.1002/jcp.1041410214

Rossi A, Coccia M, Trotta E, Angelini M, Santoro MG. Regulation of cyclooxygenase-2 expression by heat: a novel aspect of heat shock factor 1 function in human cells. PloS One. 2012;7(2):e31304. doi: https://doi.org/10.1371/journal.pone.0031304

Cruz JV, Rosa JMC, Kimani NM, Giuliatti S, Dos Santos CBR. The Role of Celecoxib as a Potential Inhibitor in the Treatment of Inflammatory Diseases – A Review. Curr Med Chem. 2022;29(17):3028-49. doi: https://doi.org/10.2174/0929867328666210910125229

Przybyła GW, Szychowski KA, Gmiński J. Paracetamol – An old drug with new mechanisms of action. Clin Exp Pharmacol Physiol. 2021 Jan;48(1):3-19. doi: https://doi.org/10.1111/1440-1681.13392