Figure 4.

In vivo experimental validation shows that sunitinib induces oxidative stress in various tissues. (a–f) Mice were fed a diet containing sunitinib or sorafenib for 14 days, after which serum and blood biomarkers and metabolite levels in the heart, platelets, and thyroid glands were analyzed. Serum troponin T levels (a) are higher, peripheral blood platelet counts (b) are lower and serum thyroid-stimulating hormone (TSH) levels (c) are higher in the sunitinib-treated group than those in the sorafenib-treated mice, indicating the development of various adverse reactions associated with sunitinib administration. Sunitinib administration also increases glycogen content (d), decreases the nicotinamide adenine dinucleotide phosphate (NADPH)/NADP⁺ ratio (e) and decreases the ratio of glutathione (GSH) to the oxidized form, GSSG, (f) in the heart, platelets and thyroid gland. Data are expressed as the mean±s.d. (n=6). *P<0.05, **P<0.01, ***P<0.001 versus control group. ^# P<0.05, ^## P<0.01, ^### P<0.001 versus the sunitinib-treated group.