Oxidative Stress Modifies the Activity of Cyclooxygenase۲, a Target of Nimesulide, in Chickens

Background: Nowadays, there is a need to investigate the potential impact of oxidative stress (OS), particularly as it relates to drug response, to ensure it is warranted and applied in veterinary medicine.Objectives: We aimed to evaluate the effect of hydrogen peroxide-induced OS on the pharmacological efficacy of nimesulide (NIM) in chickens. Methods: We assessed the NIM median effective dose (ED۵۰) using the up-and-down method, measured cyclooxygenase ۲ (COX۲) activity via ELISA, and performed spectrophotometric analysis of NIM concentrations and its pharmacokinetics. Results: Stressed chickens showed a significant (P<۰.۰۵) reduction in total antioxidant capacity (T-AOC) at the ۷th, ۱۰th, and ۱۴th days of hydrogen peroxide treatment by ۴۶, ۵۸, and ۲۲%, compared with the control group (tap water). The NIM antinociceptive efficacy increased due to a ۳۱% reduction in ED۵۰ in the stressed chickens. Consequently, there was a significant (P<۰.۰۵) inhibition in COX۲ activity in both stressed and control chickens by ۲۴ and ۳۰%, respectively. The data also showed a significant (P<۰.۰۵) modification in NIM plasma concentration in the stressed chickens compared with the control group at different measurement times. Regarding the NIM pharmacokinetic parameters, OS caused an elevation of the AUC ۰-∞, AUMC ۰-∞, Cmax, MRT, t۱/۲β, and Vss by ۱۱, ۴۲, ۱۱, ۳۵, ۴۶, and ۳۹%, respectively, whereas Kel and Cl were decreased by ۴۵ and ۸%, respectively.Conclusion: These results showed that OS modifies the pharmacodynamics and pharmacokinetics of NIM, thereby modifying its pharmacological efficacy; thus, care and adjustment of the NIM dosage are warranted for its use in stressed animals.

کلیدواژه ها:

hydrogen peroxide ، COX۲ ، Nimesulide (NIM) ، Pharmacodynamics Pharmacokinetics