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. 2021 Jul 14;29(1):139–151. doi: 10.1245/s10434-021-10376-5

Fig. 2.

Fig. 2

Influence of cisplatin, hyperthermia, and amifostine on HIPEC-induced AKI in a preclinical mouse model. a Plasma levels of creatinine, urea, and cystatin C, 48 h and 72 h after single i.p. injection of cisplatin (20 mg/kg). Data are expressed as mean ± SD; n = 6, *p < 0.05. b–d Percentage changes in creatinine (b), urea (c) and cystatin C levels (d), 72 h after i.p. perfusion (90 min) with saline (0.9%; circles) or cisplatin (75 mg/m2 in 2 L/m2 perfusate; triangles), or after single i.p. injection with cisplatin as a positive control (20 mg/kg; black circles, POSctrl). Perfusion was performed under either normothermia (38 °C, open circles, 38C; and open triangles, CPL38C) or under hyperthermic conditions (41–42 °C; gray circles, 42C; and gray triangles, CPL42C). Amifostine (200 mg/kg; diamonds, AF) was injected s.c. 15 min prior to perfusion with cisplatin at 38 °C. Individual animals are expressed as one datapoint each. n = 6 (38C, 42C, CPL42), n = 10 (CPL38, AF); *p < 0.05; nsp ≥ 0.05. e Representative PAS staining revealing histopathological changes in murine kidneys, 72 h after i.p. perfusion with saline at 38 °C (left panels, 38C), saline at 42 °C (middle left panels, 42C), cisplatin (75 mg/m2) at 38 °C (center panels, CPL38C), cisplatin at 42 °C (middle right panels, CPL42C), or cisplatin at 38 °C after amifostine treatment (200 mg/kg s.c.; right panels, AF). Note hyaline casts (#), apoptosis (*), and necrosis (x) of tubular epithelial cells in kidneys of animals perfused with cisplatin (in center and right panels), and regular proximal (>) and distal (<) tubules in kidneys of those treated with saline (left panels). Images in upper panels are taken at 100× magnification and in lower panels at 400× magnification. f, g Histomorphometric scoring of tubular injury quantity (f) and severity (g), 72 h after i.p. perfusion with saline at 38 °C (38C), saline at 42 °C (42C), cisplatin at 38 °C (CPL38C), cisplatin at 42 °C (CPL42C), or cisplatin at 38 °C after amifostine treatment (AF). Data are expressed as mean ± SD, *p < 0.05