The Study On The Anti-inflammatory Effect Of Carboxyamido-triazole And Its Possible Mechanism

Background:Carboxyamido-triazole(CAI) is an experimental anti-cancer agent developed by National Institute of Cancer (NCI) of National Institutes of Health (NIH) of the United States of American. The anti-cancer effects of CAI have been proved by many preclinical experiments and several clinical trails in different stages carried out in the United States. Our preclinical data confirmed the anti-proliferate effect of CAI in many cancer cell lines in vitro and in vivo. Further more, we found that the combination of CAI and cisplatin-vinhlastinum schedule (NP schedule) has very good therapeutic effect in stageⅡopened clinical trail of non-small cell lung cancer.In this paper, we reported the anti-inflammatory effect of CAI and the possible underlying mechanisms were examined.Methods:This study adopted cotton pellet granuloma model to determine whether CAI affected the formation of granuloma; this study adopted adjuvant-induced arthritis rat model to evaluate the effect of CAI on chronic inflammation and immunity inflammation; this study adopted enzyme linked immunosorbent assay to evaluate the effect of CAI on TNF-αand IL-1βin AA rats; this study adopted microplate assay to evaluate the effect of CAI on phospholipase A2 activity.Results:1. CAI inhibited 2% croton oil-induced ear edema at 10 mg/kg and 20 mg/kg by 18.95% and 44.61%, respectively. 2. CAI inhibited vascular permeability induced by 1ng/μl VEGF and 0.1% histamine at 20 mg/kg by 29.60% and 38.95%, respectively.3. CAI inhibited the formation of granuloma induced by planted cotton pellet. The weight of the granuloma for the control group of animals was found to be 26.77±3.56 mg/100g wt. Treatment with CAI at 10 and 20 mg/kg decreased the granuloma weight to 19.69±4.70 mg/100g wt and 17.90±2.80 mg/100g wt, respectively.4. CAI inhibited the primary lesions and secondary lesions of AIA rats at 20 mg/kg.5. CAI decreased the levels of TNF-αand IL-1βin serum of AA rats. The level of TNF-αand IL-1βfor the control group was found to be 183.45±9.32 pg/ml and 16.79±0.33 pg/ml. Treatment with CAI at 20 mg/kg decreased the levels to 15.64±7.69 pg/ml and 4.34±1.33 pg/ml, respectively.6. CAI decreased the levels of TNF-αand IL-1βin paw homogenate of AA rats. The level of TNF-αand IL-1βfor the control group was found to be 2506.75±256.69 pg/ml and 1393.84±115.12 pg/ml. Treatment with CAI at 20 mg/kg decreased the levels to 1150.98±353.77 pg/ml and 1027.51±107.69 pg/ml, respectively.7. CAI inhibited the activity of phospholipase A2 in paw homogenate of AA rats at 20 mg/kg by 37.77%, respectively.Conclusion:CAI is a potent anti-inflammation agent in many experimental animal models. The inhibition of the production of TNF-αand IL-1βand the inhibition of phospholipase A2 induced by CAI may contribute to the anti-inflammation effect of the agent.