N -Pyrazoloyl and N -thiopheneacetyl hydrazone of isatin exhibited potent anti-inflammatory and anti-nociceptive properties through suppression of NF-κB, MAPK and oxidative stress signaling in animal models of inflammation

Background Hydrazide derivatives constitute an important class of compounds for new drug development as they are reported to possess good anti-inflammatory and analgesic activity. The present study was aimed to investigate the role of newly synthesized hydrazide derivatives N -pyrazoloyl hydrazone of isatin (PHI) and N -thiopheneacetyl hydrazone of isatin (THI) in acute and chronic inflammatory pain models induced by carrageenan and complete Freud’s adjuvant (CFA). Materials PHI and THI (0.1, 1 and 10 mg/kg) pretreatments were provided intraperitoneally to male BALB/c mice prior to inflammatory inducers. Behavioral responses to inflammation and pain were evaluated by assessment of paw edema, mechanical allodynia, mechanical and thermal hyperalgesia. Cytokines production and NF-κB levels were evaluated by ELISA. Western blot analysis was performed for the detection of IκBα, p38, JNK and ERK. Hematoxylin and eosin (H&E) staining and radiographic analysis were performed to evaluate the effect of PHI and THI treatment on bone and soft tissues. Oxidative stress was determined by reduced glutathione, glutathione- S -transferase and catalase assays. Evans blue dye was used to monitor vascular protein leakage. Result PHI and THI dose dependently (0.1, 1 and 10 mg/kg) reduced inflammation and pain in mice, however, the dose of 10 mg/kg exhibited significant activity. The anti-inflammatory and analgesic effects were attributed to suppression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) production levels. PHI and THI significantly blocked CFA-induced activation of NF-κB and MAPK signaling pathways. Oxidative stress and plasma nitrite levels were reduced remarkably. The PHI and THI (10 mg/kg) treatment did not exhibit any apparent toxicity on the liver, kidney, muscles strength, and motor co‐ordination in mice. Conclusion Both PHI and THI possess significant anti-inflammatory and analgesic activity via inhibition of inflammatory mediators.