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Fig. 1 | The Journal of Physiological Sciences

Fig. 1

From: Integrative and theoretical research on the architecture of a biological system and its disorder

Fig. 1

Effect of sunitinib on metabolic pathways were simulated by sequential simulation of previously reported models. a–e The simulation result suggests that sunitinib treatment induces oxidative stress. Phosphorylase kinase (PHK) gamma-related pathways were integrated and simulated using three divided models (a) (for expanded version, see Electronic Supplementary Material figure). The pathways highlighted by black-boxed regions in a are enlarged in b–e, which also display the simulated change in the amount of different molecules as a function of free sunitinib concentration. f, g The prediction was confirmed in in vivo experiments using a mouse model. A decrease in the glutathione/oxidized glutathione (GSH/GSSG) ratio was observed in many organs of mice treated with sunitinib. In addition, elimination of oxidative stress by α-tocopherol nicotinate (α-T.N.) can prevent organ toxicities. ALT Alanine aminotransferase, GPx glutathione peroxidase, GR glutathione reductase. The results of liver toxicity analyses are shown as representative data

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