Fig. 1.

Chemotheraputic drugs when enter in living cell, it can up-regulate the levels of reactive oxygen species (ROS), which in turn phosphorylate different stress related MAPKs. These MAP kinases up-regulate the levels of pro-inflammatory cytokines such as TNF-α, IL-1, IL-6 and IL-10. Similarly, TNF-α when bind to its receptor TNFR1 it may up regulate both mRNA of MMP9 and inflammatory iNOS through phosphorylating different MAPKs, JNK, ERK1/2 and P38MAPK through activating nuclear transcription factors that are NF-Kβ, AP-1 and ATF-2. Inducible nitric oxide synthase increases concentration of nitric oxide to chronic level under pathological condition. Nitric oxide will react with super oxide anion and form peroxynitrite ONOO, which in turn increase the oxidative stress associated toxicity in multiple organs. Abbreviation: MMP9: matrix metalloproteinase 9, TNF-α: tumor necrosis factor-alpha, ROS: reactive oxygen species, iNOS: inducible nitric oxide synthase, O⁻2: superoxide anion, P³⁸MAPK: P38 mitogen activated protein kinase, JNK: c-Jun N- terminal kinases, ERK1/2: extracellular signal-regulated kinases, AP-1: activator protein 1. ATF-2: activating transcription factor-2.