TABLE 2.

Histopathological analysis of kidneys from wild-type and Nrf2-null mice after CDDO-IM pretreatment and cisplatin challenge

Wild-type and Nrf2-null mice were pretreated with CDDO-Im (oral gavage, 3, 10 mg/kg per day for 2 days) and challenged with cisplatin (20 mg/kg i.p.). Kidneys were removed 4 days after cisplatin and fixed in formalin prior to paraffin embedding and staining with hematoxylin and eosin. Kidney slices were evaluated for the severity of degeneration and necrosis in proximal tubule segments. Histopathology scoring of renal proximal tubule degeneration and necrosis by a veterinary pathologist: no injury = grade 0; minimal injury (less than 10% of cells with degeneration or necrosis) = grade 1; mild injury involving 10–25% of cells = grade 2; moderate injury involving 25–40% of cells = grade 3; marked injury involving 40–50% of cells = grade 4; severe injury involving greater than 50% of cells = grade 5. The number of mice with a particular histopathological grade is shown in each column. Mice with grades ≥2 are considered to have significant kidney injury. The ratio of mice with grades ≥2 compared to the total number of mice is presented as percentages in the right column. Histopathology grades were rank-ordered prior to statistical analysis. * represents statistically significant differences (p < 0.05) compared with genotype control mice. † represents a statistically significant difference (p < 0.05) from treatment-matched wild-type mice.

	Histopathology Grade						Percent of Mice with Grades of 2 or Greater
	0	1	2	3	4	5
Wild-type
Control	3	0	0	0	0	0	0
Cisplatin	0	3	2	0	0	1	50*
Cisplatin/CDDO-Im (3 mg/kg)	0	7	0	0	0	0	0
Cisplatin/CDDO-Im (10 mg/kg)	1	5	0	0	0	1	14
Nrf2-null
Control	3	0	0	0	0	0	0
Cisplatin	0	2	0	1	2	1	67*
Cisplatin/CDDO-Im (3 mg/kg)	0	1	1	1	0	4	86*†
Cisplatin/CDDO-Im (10 mg/kg)	0	1	3	0	0	3	86*†