Pharmacologically mediated toxicities

VI. THE EYE AS A TARGET FOR SYSTEMICALLY MEDIATED TOXIC AND PHARMACOLOGICAL EFFECTS... 

Thus trastuzumab will serve in our discussion, both as a relatively rare example of a combination toxicity associated with a bio therapeutic, as well as an example of what appears to be a pharmacologically mediated mechanism of toxicity (a more common category with biotherapeutics). 

Kelce, W.R., Monosson, E., and Gamcsik, M.P. et al. (1994). Environmental hormone disrupters—evidence that Vinclozolin developmental toxicity is mediated by antiandrogenic metabolites. Toxicology and Applied Pharmacology 126, 276-285. 

The effect of MAPK activation on cellular processes that affect cell function and the resulting pharmacology has been delineated using modem techniques such as knock-out cells and animals [1,3,6]. Activation of MAPK in inflammatory cells such as T-cells, B-cells, macrophages and eosinophils leads to expression and/or activation of pro-inflammatory genes and mediators such as interleukin-1(3 (IL-1(3), TNFa, IL-6, chemokines [e.g., IL-8, macrophage inflammatory factor-1 a, (3 (MIP-la,[3)J, MMPs and toxic molecules such as free radicals and nitric oxide [1,3]. These pro-inflammatory mediators induce cellular proliferation, differentiation, survival, apoptosis and tissue degradation/destruction and help induce chronic inflammation. Inhibition of any one or more of the MAPK family... 

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