Cyclooxygenase model

Bea F, Blessing E, Bennett BJ, et al. Chronic inhibition of cyclooxygenase-2 does not alter plaque composition in a mouse model of advanced unstable atherosclerosis. Cardiovasc Res 2003 60(1) 198-204. 

Alcantara C, Stenson WF, Steiner TS, Guerrant RL Role of inducible cyclooxygenase and prostaglandins in Clostridium difficile toxin A-induced secretion and inflammation in an animal model. J Infect Dis 2001 184 648-652. 

Jacoby RF, Seibert K, Cole CE, et al. The cyclooxygenase-2 inhibitor celecoxib is a potent preventive and therapeutic agent in the min mouse model of adenomatous polyposis. Cancer Res 2000 60 5040-5044. 

Finally, NO has significant involvement in both acute and chronic inflammation. In acute inflammation, NO promotes swelling and increased vascular permeability. In animal models of acute inflammation, NOS inhibitors have a dose-dependent protective effect. In models of chronic inflammation (arthritis), NO is detrimental and L-arginine supplementation causes inflammatory exacerbation. At a molecular level, NO stimulates inflammation by activating the cyclooxygenase enzyme. Further supportive data are provided by the observation that fluid drained from the swollen joints of people with arthritis contains peroxynitrate and other oxidation products of NO. 

ML-3000 ((2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine-5-yl)-acetic acid) is a nonantioxidant dual inhibitor of both cyclooxygenase and 5-lipoxygenase. ML-3000 has been compared to indomethacin in a number of experimental models of inflammation. The analgesic effects of ML-3000 have also been assessed in a number of animal models. Phase II studies have shown a wide range of activities, including anti-inflammatory, analgesic, antiplatelet and antiasthmatic properties (Laufer et al., 1994 Chin and Wallace, 1999). 

Drachman D. B. and Rothstein J. D. (2000). Inhibition of cyclooxygenase-2 protects motor neurons in an organotypic model of amyotrophic lateral sclerosis. Ann. Neurol. 48 792-795. 

Jhaveri, M. D., Richardson, D., Robinson, I., Garle, M. J., Patel, A., Sun, Y., Sagar, D. R., Bennett, A. J., Alexander, S. P., Kendall, D. A., Barrett, D. A., and Chapman, V. (2008). Inhibition of fatty acid amide hydrolase and cyclooxygenase-2 increases levels of endocannabi-noid related molecules and produces analgesia via peroxisome proliferator-activated receptor-alpha in a model of inflammatory pain. Neuropharmacology 55, 85—93. 

Orengo, I.F., Gerguis, J., Phillips, R., Guevara, A., Lewis, A.T., and Black, H.S., Celecoxib, a cyclooxygenase 2 inhibitor as a potential chemopreventive to UV-induced skin cancer a study in the hairless mouse model, Arch. Dermatol., 138, 751, 2002. 

Yamamoto, K., Abe, M., Katashima, M., Yamada, Y., Sawada, Y., and Iga, T., Pharmacodynamic analysis of antiplatelet effect of aspirin in the literature. Modeling based on inhibition of cyclooxygenase in the platelet and the vessel wall endothelium, Japan Journal of Hospital Pharmacy, Vol. 22, 1996, pp. 133-141. 

Maloney and Teal (1988) used ear thickness to quantify inflammatory changes produced by n-alkanes applied to ears of mice. They dosed animals twice per day for 4 days in order to produce inflammation. More recently, dithranol-induced skin irritation and the modulating effects of different pharmacologic agents, like the corticosteroids and lipoxygenase and cyclooxygenase inhibitor studies, were studies using the mouse ear model (Viluksela 1991). 

Pfizer) are selective cyclooxygenase type 2 (COX-2) inhibitors and are useful in the treatment of arthritis. The compounds exert their pharmacological effect by selectively blocking the COX-2 enzyme to produce an antiinflammatory effect without adverse gastrointestinal side effects. In addition, they also display analgesic and antipyretic activities in animal models. 

In humans, chronic inflammation of the liver is associated with hepatitis B virus (HBV) infections, and this inflammation is considered an important contributing event in HBV-induced liver cancer. In animal models, there is evidence that inflammation contributes to tumor promotion. Treatment of mouse skin with TPA produces an inflammatory response and increases the expression of proinflammatory mediators such as TNF-a, IL-la GM-CSF, and cyclooxygenase-2 (COX-2). Genetically modified mice deficient in TNFa or COX-2 are resistant to TPA-induced tumor promotion. These results indicate that the inflammatory effects of TPA are important in tumor promotion. 

---