Ameliorative Protective Influence of Etoricoxib Against Chemo Convulsions Correlates with Blood Glucose Levels in Rats

Abstract

Objective: The effect of Etoricoxib (ETOR) on the link between blood glucose and seizure prevention in chemo-convulsive rats was investigated in this study. Methods: Pentylenetetrazol (PTZ-105 mg/kg i.p.) at the CD97 dosage was administered to rats to cause seizures. ETOR (10 mg/kg p.o.) was administered for two weeks prior to seizure induction. On the 14th day, the animals were exposed to chemo convulsions, and the efficiency of ETOR in lowering clonus-type chemo convulsions (CC) as well as blood glucose levels were assessed. Morphometric analysis and chimney tests were performed to evaluate ETOR's neurotoxic profile. Actophotometer, rotarod, and hole board tests were employed for behavioral analysis. Results: When compared to control mice, pretreatment with ETOR (10 mg/kg p.o) resulted in a substantial delay in the onset of CC (p<0.05) and duration of CC (p<0.01). Acute ETOR treatment also considerably lowered blood glucose levels. The chimney test findings show that it has no effect on motor control and is not neurotoxic to the animals. Conclusion: Behavioral tests also demonstrated that, except for the diazepam-treated groups, no significant changes in muscle coordination, locomotion, or apprehensive behavior were detected in all experimental animals. Finally, the primary findings of this study showed that the PTZ group had considerably greater levels of hyperglycemia, which is reflected in the rat's early onset and longer duration of chemo-convulsions. However, ETOR medication reduced high blood glucose levels as well as the onset and duration of seizures, indicating ETOR's impact on blood glucose reduction and the relationship between blood glucose and seizure responses.

Keywords

• Blood glucose
• Chemo convulsions
• Etoricoxib
• Pentylenetetrazol
• Seizure protection

References

1. 1. Stanley S, Moheet A, Seaquist ER. Central Mechanisms of Glucose Sensing and Counterregulation in Defense of Hypoglycemia. Endocr. Rev. 2019;40(3):768-788. [CrossRef]
2. 2. Yun C, Xuefeng W. Association Between Seizures and Diabetes Mellitus: A Comprehensive Review of Literature. Curr. Diabetes Rev. 2013;9(4):350-354. [CrossRef]
3. 3. Nadeem MD, Memon S, Qureshi K, et al. Seizing the Connection: Exploring the Interplay Between Epilepsy and Glycemic Control in Diabetes Management. Curēus. Published online September 20, 2023. [CrossRef]
4. 4. Baviera M, Roncaglioni MC, Tettamanti M, et al. Diabetes mellitus: a risk factor for seizures in the elderly—a population-based study. Acta Diabetol. 2017;54(9):863-870. [CrossRef]
5. 5. Baykal M, Gökmen N, Doğan A, et al. The effects of intra-cerebroventricular administered rocuronium on the central nervous system of rats and determination of its epileptic seizure-inducing dose. Braz. J. Anesthesiol. 2017;67(1):1-5. [CrossRef]
6. 6. Vincent A, Crino PB. Systemic and neurologic autoimmune disorders associated with seizures or epilepsy. Epilepsia. 2011;52(s3):12-17. [CrossRef]
7. 7. Soltesz G, Acsadi G. Association between diabetes, severe hypoglycaemia, and electroencephalographic abnormalities. Arch. Dis. Child. 1989;64(7):992-996. [CrossRef]
8. 8. Smith WL, DeWitt DL, Garavito RM. Cyclooxygenases: Structural, Cellular, and Molecular Biology. Annu. Rev. Biochem. 2000;69(1):145-182. [CrossRef]

9. 9. Chandrasekharan N, Simmons DL. Genome Biol. 2004;5:1-7.
10. 10. Sorli CH, Zhang HJ, Armstrong MB, Rajotte RV, Maclouf J, Robertson RP. Basal expression of cyclooxygenase-2 and nuclear factor–interleukin 6 are dominant and coordinately regulated by interleukin 1 in the pancreatic islet. Proc. Natl. Acad. Sci. 1998;95(4):1788-1793.
11. 11. Robertson RP, Tsai P, Little SA, Zhang HJ, Walseth TF. Receptor-Mediated Adenylate Cyclase—Coupled Mechanism for PGE2 Inhibition of Insulin Secretion in HIT Cells. Diabetes. 1987;36(9):1047-1053. [CrossRef]
12. 12. Seaquist ER, Walseth TF, Nelson DM, Robertson RP. Pertussis Toxin–Sensitive G Protein Mediation of PGE2 Inhibition of cAMP Metabolism and Phasic Glucose-Induced Insulin Secretion in HIT Cells. Diabetes. 1989;38(11):1439-1445. [CrossRef]
13. 13. Giugliano D, Di Pinto P, Torella R, et al. A role for endogenous prostaglandin E in biphasic pattern of insulin release in humans. Am J Physiol Endocrinol Metab. 1983;245(6):E591-E597. [CrossRef]
14. 14. Luo C, Kallajoki M, Gross R, et al. Cellular distribution and contribution of cyclooxygenase (COX)-2 to diabetogenesis in NOD mouse. Cell Tissue Res. 2002;310(2):169-175. [CrossRef]
15. 15. Citraro R, Leo A, Marra R, De Sarro G, Russo E. Antiepileptogenic effects of the selective COX-2 inhibitor etoricoxib, on the development of spontaneous absence seizures in WAG/Rij rats. Brain Res. Bull. 2015;113:1-7. [CrossRef]
16. 16. Katyal J, Kumar H, Gupta YK. Anticonvulsant activity of the cyclooxygenase-2 (COX-2) inhibitor etoricoxib in pentylenetetrazole-kindled rats is associated with memory impairment. Epilepsy Behav. 2015;44:98-103. [CrossRef]
17. 17. Athmuri DN, Shiekh PA. Experimental diabetic animal models to study diabetes and diabetic complications. MethodsX. 2023;11:102474.
18. 18. Zolman P of P and BJF, Zolman JF. Biostatistics. Oxford University Press on Demand; 1993.
19. 19. Mohanalakshmi S, Kumar CA, Jayaraman R, Pooja M. Anti-diabetic, lipid lowering and antioxidant potential of Girardinia heterophylla in high fat diet and streptozotocin induced diabetic rats. Orient Pharm Exp Med. 2015;15(4):287-295.
20. 20. Jayaraman Rajangam JR, Christina AJ. Citrullus colocynthis attenuates hyperlipidemia and hyperglycemia through its anti-oxidant property against hyperlipidemic and diabetic animal models. 2013;6066.
21. 21. Christina AJ, Latha SP, Palei NN. Antihyperlipidemic and Antio Citrullus colocynthis fruits on Hyperlipidemic and STZ-Induc. Int J Pharma Res Health Sci. 2018;6(5):2808-2813.
22. 22. Borowicz KK, Luszczki JJ, Duda AM, Czuczwar SJ. Effect of Topiramate on the Anticonvulsant Activity of Conventional Antiepileptic Drugs in Two Models of Experimental Epilepsy. Epilepsia. 2003;44(5):640-646. [CrossRef]
23. 23. Zareie P, Sadegh M, Palizvan MR, Moradi-Chameh H. Anticonvulsive effects of endocannabinoids; an investigation to determine the role of regulatory components of endocannabinoid metabolism in the Pentylenetetrazol induced tonic- clonic seizures. Metab. Brain Dis. 2018;33(3):939-948. [CrossRef]
24. 24. Szkutnik-Fiedler D, Kus K, Balcerkiewicz M, Grześkowiak E, Nowakowska E, Burda K, Ratajczak P, Sadowski C. Concomitant use of tramadol and venlafaxine—Evaluation of antidepressant-like activity and other behavioral effects in rats. Pharmacol. Res. 2012;64(6):1350-1358.
25. 25. Dews PB. The Measurement of The Influence of Drugs on Voluntary Actıvıty in Mıce. Br J Pharmacol Chemother. 1953;8(1):46-48. [CrossRef]
26. 26. Takeda H, Tsuji M, Matsumiya T. Changes in head-dipping behavior in the hole-board test reflect the anxiogenic and/or anxiolytic state in mice. Eur. J. Pharmacol. 1998;350(1):21-29. [CrossRef]
27. 27. Nolan NA, Parkes MW. The effects of benzodiazepines on the behaviour of mice on a hole-board. J. Psychopharmacol. 1973;29(3):277-288. [CrossRef]
28. 28. Kliethermes C, Crabbe J. Pharmacological and genetic influences on hole-board behaviors in mice. Pharmacol. Biochem. Behav. 2006;85(1):57-65. [CrossRef]
29. 29. Rajangam J, Lavanya O. Effect of Rosuvastatin on learning and memory in scopolamine induced amnesia in Mice. Trends in Medicine. 2018;18(2). [CrossRef]
30. 30. Sk K, Pc D. Influence of intraventricular administration of norepinephrine, dopamine and 5-hydroxytryptamine on motor activity of rats. PubMed. 1975;63(3):462-468. [CrossRef]
31. 31. Dunham NW, Miya TS. A Note on a Simple Apparatus for Detecting Neurological Deficit in Rats and Mice**College of Pharmacy, University of Nebraska, Lincoln 8. J. Am. Pharm. Assoc. 1957;46(3):208-209. [CrossRef]
32. 32. Schwechter EM, Velís̆Ková J, Velís̆Ek L. Correlation between extracellular glucose and seizure susceptibility in adult rats. Ann. Neurol. 2002;53(1):91-101. [CrossRef]
33. 33. Greene AE, Todorova MT, McGowan R, Seyfried TN. Caloric Restriction Inhibits Seizure Susceptibility in Epileptic EL Mice by Reducing Blood Glucose. Epilepsia. 2001;42(11):1371-1378. [CrossRef]
34. 34. Bartolini E, Ferrari AR, Fiori S, Della Vecchia S. Glycaemic Imbalances in Seizures and Epilepsy of Paediatric Age: A Literature Review. J. Clin. Med. 2023;12(7):2580. [CrossRef]
35. 35. Yorulmaz H, Kaptan E, Seker FB, Oztas B. Type 1 diabetes exacerbates blood–brain barrier alterations during experimental epileptic seizures in an animal model. Cell Biochem. Funct. 2015;33(5):285-292. [CrossRef]
36. 36. Scherer C. Seizures and non-ketotic hyperglycemia. Presse Med. (Paris, France: 1983). 2005;34(15):1084-1086.
37. 37. Tiamkao S, Pratipanawatr T, Tiamkao S, Nitinavakarn B, Chotmongkol V, Jitpimolmard S. Seizures in nonketotic hyperglycaemia. Seizure. 2003;12(6):409-410. [CrossRef]
38. 38. Wang C, Hsieh PF, Chen CC, et al. Hyperglycemia with Occipital Seizures: Images and Visual Evoked Potentials. Epilepsia. 2005;46(7):1140-1144. [CrossRef]
39. 39. Moien-Afshari F, Téllez-Zenteno JF. Occipital seizures induced by hyperglycemia: A case report and review of literature. Seizure. 2009;18(5):382-385. [CrossRef]
40. 40. Seo DW, Na DG, Na DL, Moon SY, Hong SB. Subcortical Hypointensity in Partial Status Epilepticus Associated with Nonketotic Hyperglycemia. J. Neuroimaging. 2003;13(3):259-263. [CrossRef]
41. 41. Miki T, Seino S. Roles of KATP channels as metabolic sensors in acute metabolic changes. J. Mol. Cell. Cardiol. 2005;38(6):917-925. [CrossRef]
42. 42. Weiss SL, Alexander J, Agus MSD. Extreme Stress Hyperglycemia During Acute Illness in a Pediatric Emergency Department. Pediatr. Emerg. Care. 2010;26(9):626-632. [CrossRef]
43. 43. Chou HF, Shen EY, Kuo YT. Utility of Laboratory Tests for Children in the Emergency Department With a First Seizure. Pediatr. Emerg. Care. 2011;27(12):1142-1145. [CrossRef]
44. 44. Lee JY, Kim JH, Cho HR, et al. Children Experiencing First-Time or Prolonged Febrile Seizure Are Prone to Stress Hyperglycemia. J. Child Neurol. 2015;31(4):439-443. [CrossRef]