Nephrotoxcicity adverse outcome pathway (Homo sapiens)

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Adverse outcome pathway depicting events of nephrotoxicity leading to tubular cell injury and death. The molecular initiating event is the activation of the OCT2 and CRT1 receptors which then leads to the key events. The damage can take place in various ways, including DNA damage, apoptosis and induction of inflammation. These processes are represented as key events. DNA damage induction leads to reactive oxygen species production by the activation of p53. Furthermore, the occurrence of mitochondrial and endoplasmic reticulum stress causes the activation of both caspase-dependent and independent apoptotic pathways. Another key event is the activation of toll-like receptor 4 which causes NF-kB pathway activation and production of proinflammatory cytokines and chemokines. This process causes inflammation which eventually leads to cell injury and death. Moreover, the production of reactive oxygen species can cause further production of pro-inflammatory mediators and can also induce apoptosis.