We studied the interaction of S-methylisothiourea (a selective inducible nitric oxide synthase in... more We studied the interaction of S-methylisothiourea (a selective inducible nitric oxide synthase inhibitor) with rofecoxib (a selective cyclooxygenase-2 inhibitor) and mefenamic acid (a non-selective cyclooxygenase inhibitor) in adjuvant-induced arthritis in female albino Wistar rats, applying the isobolographic analysis. Each drug was effective in reducing the progressive increase in paw volume less than 50% except rofecoxib, when used alone. Log dose-response curve was obtained for each drug along with the corresponding ED 25. Following isobolographic analysis, combination of S-methylisothiourea with rofecoxib and mefenamic acid revealed supra-additive or synergistic interaction. Experimental ED 25 of the combinations was significantly lower than the theoretical ED 25 of the corresponding drug combination which substantiated the synergistic type of interaction between inducible nitric oxide synthase and cyclooxygenase in adjuvant-induced arthritis in female albino rats. Results suggest that NO regulates the cyclooxygenase enzyme activity as the activity of cyclooxygenase enzymes in the LPS-stimulated leukocyte lysates was significantly low or hardly detectable in the presence of varying concentrations of S-methylisothiourea. Simultaneous inhibition of inducible nitric oxide synthase and cyclooxygenase appears to offer an alternative approach for ameliorating the progression of arthritis.
An interaction between nitric oxide (NO) and cyclooxygenases (COX) in the production of prostagla... more An interaction between nitric oxide (NO) and cyclooxygenases (COX) in the production of prostaglandins in carrageenan-induced inflammation has been established. However, limited information is available about the interaction between inducible NO synthase (iNOS) and COX inhibitors in pain perception. Therefore, in the present study we assessed the nature of the interaction between S-methylisothiourea (a moderately selective iNOS inhibitor) with rofecoxib (selective COX-2 inhibitor) and mefenamic acid (a nonselective COX inhibitor) in formalin- induced pain in mice. The dose-response relation of S-methylisothiourea, rofecoxib, mefenamic acid, and their combination was studied in the late phase of formalin-induced pain in mice over the time spent in licking the hindpaw after formalin injection. The interaction was evaluated by simultaneous administration of fixed proportions of S-methylisothiourea with each COX inhibitor and the nature of the interaction was determined by isobolographic analysis. Each drug alone produced a dose-dependent suppression of the late stage of formalin-induced behaviors with rank order of potency being rofecoxib > mefenamic acid…
We studied the interaction of S-methylisothiourea (a selective inducible nitric oxide synthase in... more We studied the interaction of S-methylisothiourea (a selective inducible nitric oxide synthase inhibitor) with rofecoxib (a selective cyclooxygenase-2 inhibitor) and mefenamic acid (a non-selective cyclooxygenase inhibitor) in adjuvant-induced arthritis in female albino Wistar rats, applying the isobolographic analysis. Each drug was effective in reducing the progressive increase in paw volume less than 50% except rofecoxib, when used alone. Log dose-response curve was obtained for each drug along with the corresponding ED 25. Following isobolographic analysis, combination of S-methylisothiourea with rofecoxib and mefenamic acid revealed supra-additive or synergistic interaction. Experimental ED 25 of the combinations was significantly lower than the theoretical ED 25 of the corresponding drug combination which substantiated the synergistic type of interaction between inducible nitric oxide synthase and cyclooxygenase in adjuvant-induced arthritis in female albino rats. Results suggest that NO regulates the cyclooxygenase enzyme activity as the activity of cyclooxygenase enzymes in the LPS-stimulated leukocyte lysates was significantly low or hardly detectable in the presence of varying concentrations of S-methylisothiourea. Simultaneous inhibition of inducible nitric oxide synthase and cyclooxygenase appears to offer an alternative approach for ameliorating the progression of arthritis.
An interaction between nitric oxide (NO) and cyclooxygenases (COX) in the production of prostagla... more An interaction between nitric oxide (NO) and cyclooxygenases (COX) in the production of prostaglandins in carrageenan-induced inflammation has been established. However, limited information is available about the interaction between inducible NO synthase (iNOS) and COX inhibitors in pain perception. Therefore, in the present study we assessed the nature of the interaction between S-methylisothiourea (a moderately selective iNOS inhibitor) with rofecoxib (selective COX-2 inhibitor) and mefenamic acid (a nonselective COX inhibitor) in formalin- induced pain in mice. The dose-response relation of S-methylisothiourea, rofecoxib, mefenamic acid, and their combination was studied in the late phase of formalin-induced pain in mice over the time spent in licking the hindpaw after formalin injection. The interaction was evaluated by simultaneous administration of fixed proportions of S-methylisothiourea with each COX inhibitor and the nature of the interaction was determined by isobolographic analysis. Each drug alone produced a dose-dependent suppression of the late stage of formalin-induced behaviors with rank order of potency being rofecoxib > mefenamic acid…
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Papers by Vamsi Krishna