Martínez-Martínez AL, González-Trujano ME, López-Muñoz FJ

Language: Spanish
References: 29
Page: 249-256
PDF size: 284.94 Kb.

ABSTRACT

Introduction: Nowadays the number of patients that complements its drug treatment through the use of alternative medicine with analgesic purpose grows exponentially; although the presence of supra-additive or additive effect can be positive, the undesirable effects might also be promoted and stays away from the therapeutic utility. Objective: The antinociceptive effects of the bioflavonoid hesperidin and the non-steroidal anti-inflammatory drug ketorolac administrated in combination were determined in an experimental model of gouty arthritis. Material and methods: Nociception was induced by the intra-articular injection of uric acid at 20% to induce dysfunction. When the functionality was zero animals received pharmacologic treatment and then the recovery of functionality was assessed as an expression of antinociception. The data were interpreted using the «surface of synergistic interaction» analysis to establish the nature of the interaction. Results: Between the tested combinations, hesperidin (562.3 mg/kg) and ketorolac (0.56 mg/kg) produced an antinociceptive effect individually of 43.9 ± 18.8 area units (au) and 100.8 ± 18.7 area units, respectively. Moreover, the antinociceptive effect of the combination of these doses was significantly higher than expected from the sum of individual effects manifesting a supra-additive effect with 228.3 ± 30.8 area units. Gastric damage that is commonly produced during administration of NSAIDs was significantly reduced in presence of the bioflavonoid. Discussion: This is the first study to demonstrate that the combination of hesperidin + ketorolac potentiates the antinociceptive effects and reduce adverse effects. Conclusions: The combination of hesperidin + ketorolac preferentially promotes additive and supra-additive antinociceptive responses suggesting its therapeutic potential in treatment of gouty arthritis pain.

REFERENCES

1. Linares-Borges A, Millán-Vázquez PM, Jiménez-Fernández L, Chala-Tandrón JM, Alermán-Aguilar H, Betancourt-Rodríguez BY et al. Interacciones medicamentosas. Acta Farm Bonaerense. 2002;21:139-148.

2. Morii S. Research for vitamin. P J Biochem Tokyo. 1939;29:487-501.

3. Fernández SP, Wasowski C, Paladini AC, Marder M. Synergistic interaction between hesperidin, a natural flavonoid, and diazepam. Eur J Pharmacol. 2005;512:189-198.

4. Guzmán-Gutiérrez SL, Navarrete A. Pharmacological exploration of the sedative mechanism of hesperidin identified as the active principle of Citrus sinensis flowers. Planta Med. 2009;75:295-301.

5. Hirata A, Murakami Y, Shoji M, Kadoma Y, Fujisawa S. Kinetics of radical-scavenging activity of hesperetin and hesperidin and their inhibitory activity on COX-2 expression. Anticancer Res. 2005;25:3367-3374.

6. Zhang YQ, Gao X, Ji GC, Huang YL, Wu GC, Zhao ZQ. Expression of 5-HT1A receptors mRNA in rat lumbar spinal dorsal horn neurons after peripheral inflammation. Pain. 2002;98:287-295.

7. Tanaka T, Makita H, Ohnishi M. Chemoprevention of 4-nitroquinoline-1-oxide-induced oral carcinogenesis in rats by flavonoids diosmin and hesperidin, each alone and in combination. Cancer Res. 1997;587:246-252.

8. Galati EM, Monforte MT, Kirjavainen S, Forertieri AM, Tripodo MM. Biological effects of hesperidin, a citrus flavonoid. (note I): anti-inflammatory and analgesic activity. Farmaco. 1994;49:709-712.

9. Benavente-García O, Castillo J. Update and uses and properties of citrus flavonoids: new findings in anticancer, cardiovascular, and anti-inflammatory activity. J Agric Food Chem. 2008;56:6185-6205.

10. Garg A, Garg S, Zaneveld LJD, Singla AK. Chemistry and pharmacology of the citrus bioflavonoid hesperidin. Phytother Res. 2001;15:655-669.

11. Kokkalou E, Kapetanidis I. Flavonoids of the aereal parts of acinos suaveolens. Pharm Acta Helv. 1988;636:170-173.

12. Al-Sereiti MR, Abu-Amer KM, Sen P. Pharmacology of rosemary (Rosmarinus officinalis Linn) and its therapeutic potentials. Indian J Exp Biol. 1999;3:124-130.

13. Altinier G, Sosa S, Aquino RP, Mencherini T, Della Loggia R, Tubaro A. Characterization of topical anti-inflammatory compounds in Rosmarinus officinalis Linn. J Agric Food Chem. 2007;55:1718-1723.

14. Peng CH, Su JD, Chyau CC, Sung TY, Ho SS, Peng CC et al. Supercritical fluid extracts of rosemary leaves exhibit potent anti-inflammation and anti-tumor effects. Biosci Biotechnol Biochem. 2007;71:2223-2232.

15. González-Trujano ME, Peña EI, Martínez AL, Moreno J, Guevara-Fefer P, Déciga-Campos M et al. Evaluation of the antinociceptive effect of Rosmarinus officinalis Linn: using three different experimental models in rodents. J Ethnopharmacol. 2007;111:476-482.

16. Okamura N, Haraguchi H, Hashimoto K, Yagi A. Flavonoids in Rosmarinus officinalis leaves. Phytochem. 1994;37:1463-1466.

17. Martínez AL, González-Trujano ME, Chávez M, Pellicer F, Moreno J, López-Muñoz FJ. Hesperidin produces antinociceptive response and synergistic interaction with ketorolac in an arthritic gout-type pain in rats. Pharmacol Biochem Behav. 2011;97:683-689.

18. López-Muñoz FJ, Salazar LA, Castañeda-Hernández G, Villarreal JE. A new model to assess analgesic activity: pain-induced functional impairment in the rat (PIFIR). Drug Dev Res. 1993;28:169-175.

19. López-Muñoz FJ. Surface of synergistic interaction between dipyrone and morphine in the PIFIR model. Drug Dev Res. 1994;33:26-32.

20. Covino BG, Dubner R, Gybels J, Kosterlitz HW, Liebeskind JC, Sternbach RA et al. Ethical standards for investigation of experimental pain in animals. Pain. 1980;9:141-143.

21. Zimmermann M. The guidelines on ethical standards for investigation of experimental pain in animals. Pain. 1983;16:109-110.

22. Hernández-Delgadillo GP, López-Muñoz FJ, Salazar LA, Cruz SL. Morphine and dipyrone co-administration delays tolerance development and potentiates antinociception. Eur J Pharmacol. 2003;469:71-79.

23. Déciga-Campos M, Guevara U, Díaz MI, López-Muñoz FJ. Enhancement of antinociception by co-administration of an opioid drug (morphine) and a preferential cyclooxygenase-2 inhibitor (rofecoxib) in rats. Eur J Pharmacol. 2003;460:99-107.

24. López-Muñoz FJ, Godínez-Chaparro B, Huerta-Cruz JC, Guevara-López U, Domínguez-Ramírez AM, Cortés-Arroyo AR. The antinociceptive efficacy of morphine, metamizol, or their combination in an experimental rat model with different levels of inflammatory pain. Pharmacol Biochem Behav. 2008;91:196-201.

25. De la O-Arciniega M, Díaz-Reval MI, Cortés-Arroyo AR, Domínguez-Ramírez AM, López-Muñoz FJ. Anti-nociceptive synergism of morphine and gabapentin in neuropathic pain induced by chronic constriction injury. Pharmacol Biochem Behav. 2009;92:457-464.

26. López-Muñoz FJ, Díaz-Reval MI, Terrón JA, Déciga-Campos M. Analysis of the analgesic interactions between ketorolac and tramadol durin arthritic nociception in rat. Eur J Pharmacol. 2004;484:157-165.

27. López JR, Domínguez-Ramírez AM, Cook HJ, Bravo G, Díaz-Reval MI, Déciga-Campos M et al. Enhancement of antinociception by co-administration of ibuprofen and caffeine in arthritic rats. Eur J Pharmacol. 2006;544:31-38.

28. Martínez AL, González-Trujano ME, Aguirre-Hernández E, Moreno J, Soto-Hernández M, López-Muñoz FJ. Antinociceptive activity of Tilia americana var. mexicana inflorescences and quercetin in the formalin test and in an arthritic pain model in rats. Neuropharmacol. 2009;56:564-571.

29. Forrest JB, Camu F, Geer IA, Kehlet H, Abdalla M, Bonnet F et al. Ketorolac, diclofenac, and ketoprofen are equally safe for pain relief after surgery. Br J Anaesth. 2002;88:227-233.