Isobolographic analysis of analgesic interactions of silymarin with ketamine in mice

PDF
DOI: https://doi.org/10.12681/jhvms.23653
Keywords:
silymarin ketamine analgesia isobolographic hotplate mice
A.S. NASER
Department of physiology, biochemistry and pharmacology, Faculty of Veterinary Medicine, University of Mosul, Mosul, Iraq
Y. ALBADRANY
Department of physiology, biochemistry and pharmacology, Faculty of Veterinary Medicine, University of Mosul, Mosul, Iraq
K.A. SHAABAN
sezsen@uludag.edu.tr
Abstract

The present study was undertaken to explore the analgesic effect of silymarin and ketamine alone or in combination in mice. Analgesia was measured by using a hot plate and the writhing test. The up-and-down method was used to determine the median effective analgesic dosages (ED50s) of silymarin and ketamine administered intraperitoneally (ip) either alone or together. The ED50s of both drugs were analyzed isobolographically to determine the type of pharmacological interaction between them. The analgesic ED50s for silymarin and ketamine in mice were 57.22 and 1.96 mg/kg, ip, respectively. Concomitant administration of the silymarin and ketamine at fixed ration (0.5:0.5) of their individual ED50s was 38.4 mg/kg and 1.28 mg/kg, ip, respectively. Silymarin and ketamine at fixed ration (1:1) of their individual ED50s were 47.54 mg/kg and 1.58 mg/kg, ip, respectively . Depending on the isobolographic analysis and calculating Y value, the type of pharmacological interaction between silymarin and ketamine at a ratio of 0.5:0.5 and 1:1 of their analgesic ED50 values of each drug , was antagonistic .In the writhing test the concomitant administration of silymarin and ketamine at 120mg/kg and 4mg/kg , ip, respectively reduce significantly the numbers of writhing in compare with silymarin120 mg/kg,ip and ketamine 4mg/kg, ip separately. The results suggest that the co-administration of silymarin and ketamine was ineffective to reduce the central pain while the concomitant administration of silymarin and ketamine was effective to reduce the visceral pain.

Article Details
  • Section
  • Research Articles
Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Authors who publish with this journal agree to the following terms:

· Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution Non-Commercial License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.

· Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g. post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.

· Authors are permitted and encouraged to post their work online (preferably in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.

Downloads
Download data is not yet available.
References
Abenavoli, L., Capasso, R., Milic, N., & Capasso, F. (2010). Milk thistle in liver diseases: past, present, future. Phytotherapy Research, 24(10), 1423–1432.
Acharya, S. D., Ullal, P., Padiyar, S., Rao, Y. D., Upadhyaya, K., Pillai, D., & Raj, V. (2011). Analgesic effect of extracts of Alpiniagalanga rhizome in mice. Journal of Chinese Integratve Medicine, 9(1), 100–104.
Aiello, S. E., & Mays, A. (1998). The Merck Veterinary Manual. Merck & Co. Inc., Whitehouse Station, NJ, 2032–2033.
Amin, M. M., & Arbid, M. S. (2015). Estimation of the novel antipyretic, anti-inflammatory, antinociceptive and antihyperlipidemic effects of silymarin in Albino rats and mice. Asian Pacific Journal of Tropical Biomedicine, 5(8), 619–623.
Barrot, M. (2012). Tests and models of nociception and pain in rodents. Neuroscience, 211, 39–50.
Bhutia, Y., Vijayaraghavan, R., & Pathak, U. (2010). Analgesic and anti-inflammatory activity of amifostine, DRDE-07, and their analogs, in mice. Indian Journal of Pharmacology, 42(1), 17. https://doi.org/10.4103/0253-7613.62401
Carter, J., & Story, D. A. (2013). Veterinary and human anaesthesia: an overview of some parallels and contrasts. Anaesthesia and Intensive Care, 41(6), 710–718.
Coetzee, J. F. (2013). A review of analgesic compounds used in food animals in the United States. Veterinary Clinics: Food Animal Practice, 29(1), 11–28.
Corchete, P. (2008). Silybum marianum (L.) Gaertn: the source of silymarin. In Bioactive Molecules and Medicinal Plants (pp. 123–148). Springer.
Cornick-Seahorn JL: (2001). Veterinary Anesthesia, 2001. Butterworth-Heinemann, Woburn, MA.
Dambisya YM, L. T. (1994). Antinociceptive effects of ketamine-opioid combinations in the mouse tail flick test. Methods Find Exp Clin Pharmacol, 16, 179–184.
Danion, J. M., Diemunsch, P., & Brandt, C. (2000). Effect of a subanesthetic dose of ketamine on memory and conscious awareness in healthy volunteers. Psychopharmacology, 152(3), 283–288.
de Campos Buzzi F, Fracasso M, Filho VC, E. R., & del Olmo E, S. F. A. (2010). New antinociceptiveagents related to dihydrosphingosine. Pharmacol Rep, 62, 849–857.
de Campos Buzzi, F., Fracasso, M., Cechinel Filho, V., Escarcena, R., del
Olmo, E., & San Feliciano, A. (2010). New antinociceptive agents related to dihydrosphingosine. Pharmacological Reports, 62(5),849–857.
Dixon, W. J. (1980). Efficient analysis of experimental observations. Annual Review of Pharmacology and Toxicology, 20(1), 441–462.
El Mohsen, M. M. A., Kuhnle, G., Rechner, A. R., Schroeter, H., Rose, S., Jenner, P., & Rice-Evans, C. A. (2002). Uptake and metabolism of epicatechin and its access to the brain after oral ingestion. Free Radical Biology and Medicine, 33(12), 1693–1702.
Fanoudi, S., Alavi, M. S., Karimi, G., & Hosseinzadeh, H. (2018). Milk thistle ( Silybum Marianum ) as an antidote or a protective agent against natural or chemical toxicities: a review . Drug and Chemical Toxicology, 0(0), 1–15. https://doi.org/10.1080/01480545.2018.1485687
Ferruzzi, M. G., Lobo, J. K., Janle, E. M., Cooper, B., Simon, J. E., Wu, Q.-L., … Pasinetti, G. M. (2009). Bioavailability of gallic acid and catechins from grape seed polyphenol extract is improved by repeated dosing in rats: implications for treatment in Alzheimer’s disease. Journal of Alzheimer’s Disease, 18(1), 113–124.
Fiebrich, F., & Koch, H. (1979). Silymarin, an inhibitor of lipoxygenase. Experientia, 35(12), 1548–1550. https://doi.org/10.1007/BF01953184
Gawade, S. (2012). Acetic acid induced painful endogenous infliction in writhing test on mice. Journal of Pharmacology and Pharmacotherapeutics, 3(4), 348. https://doi.org/10.4103/0976-500x.103699
Gonzalez, C., Zegpi, C., Noriega, V., Prieto, J. C., & Miranda, H. F. (2011). Synergism between dexketoprofen and meloxicam in an orofacial formalin test was not modified by opioid antagonists. Pharma cological Reports, 63(2), 433–440.
Gupta, A., Devi, L. A., & Gomes, I. (2011). Potentiation of μ‐opioid receptor‐mediated signaling by ketamine . Journal of Neurochemistry, 119(2), 294–302.
Gupta, O. P., Sing, S., Bani, S., Sharma, N., Malhotra, S., Gupta, B. D., … Handa, S. S. (2000). Anti-inflammatory and anti-arthritic activities of silymarin acting through inhibition of 5-lipoxygenase. Phytomedicine, 7(1), 21–24. https://doi.org/10.1016/S0944-7113(00)80017-3
Gupta, V. K. (2006). Metoclopramide is not an analgesic: reflection on premature scientific conclusion. Int J Clin Pract, 60, 744.
Hassani, F. V., Rezaee, R., Sazegara, H., Hashemzaei, M., Shirani, K., & Karimi, G. (2015). Effects of silymarin on neuropathic pain and formalin-induced nociception in mice. Iranian Journal of Basic Medical Sciences, 18(7), 715.
Herz, W., Heywood, V. H., Harborne, J. B., & Turner, B. L. (1977). The biology and chemistry of compositae. Academic Press, London, 11, 337–338.
Hsu, W. H. (2013). Handbook of veterinary pharmacology. John Wiley & Sons.
Hussain, S. A., Jassim, N. A., Numan, I. T., Al-Khalifa, I. I., & Abdullah, T. A. (2009). Anti-inflammatory activity of silymarin in patients with knee osteoarthritis. A comparative study with piroxicam and meloxicam. Saudi Medical Journal, 30(1), 98–103.
Irifune, M., Sato, T., Kamata, Y., Nishikawa, T., Nomoto, M., Fukuda, T., & Kawahara, M. (1998). Inhibition by diazepam of ketamine-induced hyperlocomotion and dopamine turnover in mice. Canadian Journal of Anaesthesia, 45(5), 471–478.
Jadhav, G. B., Upasani, C. D., & others. (2009). Analgesic effect of silymarin in experimental induced pain in animal models. Journal of Pharmacy Research, 2(8), 1276–1278.
Jadhav, G., & Upasani, C. (2009). Analgesic effect of silymarin in experimental induced pain in animal models. Journal of Pharmacy Research, 2(8), 1276.
Jain, N. K., Kulkarni, S. K., & Singh, A. (2001). Differential antinociceptive effect of cyclooxygenase inhibitors in acetic acid-induced chemonociceptionin mice. Analgesia, 5(3–4), 211–216.
Koster, R. (1959). Acetic acid for analgesic screening. Fed Proc, 18, 412.
Kren, V., & Walterová, D. (2005). Silybin and silymarin--new effects and
applications. Biomedical Papers of the Medical Faculty of the University
Palacký, Olomouc, Czechoslovakia, 149(1), 29–41. https://doi.org/10.5507/bp.2005.002
Le Bars, D., Gozariu, M., & Cadden, S. W. (2001). Animal models of nociception. Pharmacological Reviews, 53(4), 597–652.
Luper, S. (1998). A review of plants used in the treatment of liver disease: part 1. Alternative Medicine Review: A Journal of Clinical Therapeutic, 3(6), 410–421.
Manna, S. K., Mukhopadhyay, A., Van, N. T., & Aggarwal, B. B. (1999). Silymarin suppresses TNF-induced activation of NF-$κ$B, c-Jun N-terminal kinase, and apoptosis. The Journal of Immunology, 163(12), 6800–6809.
Mateen, S., Raina, K., & Agarwal, R. (2013). Chemopreventive and anti-cancer efficacy of silibinin against growth and progression of lung cancer. Nutrition and Cancer, 65(SUPPL.1), 3–11. https://doi.org/10.1080/01635581.2013.785004
Mohammad, F. K., Al-Baggou, B. K., & Naser, A. S. (2012). Antinociception by metoclopramide, ketamine and their combinations in mice. Pharmacological Reports, 64(2), 299–304. https://doi.org/10.1016/S1734-1140(12)70768-5
Mohammad, F. K., Al-Zubaidy, M. H. I., & Alias, A. S. (2007). Sedative and hypnotic effects of combined administration of metoclopramide and ketamine in chickens. Lab Animal, 36(4), 35.
Naser, A. S., & Amin, Y. M. (2019). Analgesic effect of silymarin in chicks. Iraqi Journal of Veterinary Sciences, 33(2), 273–276.
Nieuwenhuijs, D., Dahan, A., Kieffer, B. L., Matthes, H. W. D., Teppema,L. J., Sarton, E., & Olievier, C. (2004). The Involvement of the μ-Opioid Receptor in Ketamine-Induced Respiratory Depression and Antinociception. Anesthesia & Analgesia, 93(6), 1495–1500. https://doi.org/10.1097/00000539-200112000-00031
Ottai, M. E. S., & Abdel-Moniem, A. S. H. (2006). Genetic parameter variations among milk thistle, Silybum marianum varieties and varietal sensitivity to infestation with seed-head weevil, Larinus latus Herbst. International Journal of Agriculture and Biology, 6, 862–866.
Persson, J. (2013). Ketamine in pain management. CNS Neuroscience & Therapeutics, 19(6), 396–402.
Raffa, R. B. (2001). Pharmacology of oral combination analgesics: rational therapy for pain. Journal of Clinical Pharmacy and Therapeutics, 26(4), 257–264.
Rang, H. P., Dale, M. M., Ritter, J. M., & Moore, P. K. (2003). Pharmacology. 5th. London: Churchill Livingston, 490–502.
Reder, B. S., Trapp, L. D., & Troutman, K. C. (1980). Ketamine suppression of chemically induced convulsions in the two-day-old white leghorn cockerel. Anesthesia and Analgesia, 59(6), 406–409.
Ricciotti, E., & FitzGerald, G. A. (2011). Prostaglandins and inflammation.
,. Arteriosclerosis, Thrombosis, and Vascular Biology, 31(5), 986-1000. .
Rodriguez-Mateos, A., Vauzour, D., Krueger, C. G., Shanmuganayagam, D., Reed, J., Calani, L., … Crozier, A. (2014). Bioavailability, bioactivity and impact on health of dietary flavonoids and related compounds: an update. Archives of Toxicology, 88(10), 1803–1853.
Sabiu, S., Sunmonu, T. O., Ajani, E. O., & Ajiboye, T. O. (2015). Combined
administration of silymarin and vitamin C stalls acetaminophen- mediated hepatic oxidative insults in Wistar rats. Revista Brasileira de Farmacognosia, 25(1), 29–34. https://doi.org/10.1016/j.bjp.2014.11.012
Sahib, A. S. (2011). Antinociceptive effect of silymarin in experimental
animal. Al-Kindy College Medical Journal, 7(2), 91–94.
Semalty, A., Semalty, M., Rawat, M. S. M., & Franceschi, F. (2010). Supramolecular phospholipids--polyphenolics interactions: The PHYTOSOME ®strategy to improve the bioavailability of phytochemicals. Fitoterapia, 81(5), 306–314.
Short, C. E. (1992). Alpha 2 agents in animals. Sedation, analgesia and anaesthesia. Brilling Hill. Inc., Santa Barbara.
Škottová, N., Večevra, R., Urbánek, K., Vávna, P., Walterová, D., & Cvak, L. (2003). Effects of polyphenolic fraction of silymarin on lipoprotein profile in rats fed cholesterol-rich diets. Pharmacological Research, 47(1), 17–26.
Soon, K. J., Young, J. J., Song-Kyu, P., Kyu-Hwan, Y., & Mook, K. H. (2004). Protection against lipopolysaccharide-induced sepsis and inhibition of interleukin-1b and prostaglandin E2 synthesis by silymarin. Biochemical Pharmacology, 67(1), 175–181.
Stolf, A. M., Cardoso, C. C., & Acco, A. (2017). Effects of silymarin on diabetes mellitus complications: a review. Phytotherapy Research, 31(3), 366–374.
Tallarida, R. J. (1992). Statistical analysis of drug combinations for synergism. Pain, 49(1), 93–97.
Tawfic, Q. A. (2013). A review of the use of ketamine in pain management. Journal of Opioid Management, 9(5), 379–388.
Tricklebank, M. D., Singh, L., Oles, R. J., Preston, C., & Iversen, S. D. (1989). The behavioural effects of MK-801: a comparison with antagonists acting non-competitively and competitively at the NMDA receptor. European Journal of Pharmacology, 167(1), 127–135.
Vahdati Hassani, F., Rezaee, R., Sazegara, H., Hashemzaei, M., Shirani, K., & Karimi, G. (2015). Effects of silymarin on neuropathic pain and formalin-induced nociception in mice. Iranian Journal of Basic Medical Sciences, 18(7), 715–720.
Woolfe, G., & Macdonald, A. D. (1944). the Evaluation of the Analgesic Action of Pephidine Hydrochloride (Demerol). The Journal of Pharmacology and Experimental Therapeutics, 80(3), 300–307.
Yaksh, T. L. (1994). Interaction of spinal modulatory receptor systems. Progress in Pain Research and Management, 1, 151–171.