Fig. 5.

Co-treatment with vitamin E abrogates the therapeutic effect of 11beta-dichloro in the early onset mouse model of ADPKD. (A) Representative whole kidney H&E scans of vehicle-treated (Left), 11beta-dichloro-treated (Middle), and 11beta-dichloro+vitamin E co-treated (Right) kidneys. (Scale bar, 1 mm.) Vehicle-only or 11beta-dichloro (10 mg/kg) was given i.p. daily from P10-P23 and mice were analyzed at P24. In addition to the 11beta-dichloro (10 mg/kg) injection, the third group received vitamin E (DL α-tocopherol acetate, 20 IU/mL) in drinking water. Morphological parameters—(B) two kidney/body weight ratio and (C) cystic index—and the functional parameter—(D) BUN—show that the addition of vitamin E abolishes the PKD amelioration afforded by the 11beta-dichloro treatment alone (n = 4 for all groups). (E) Apoptosis was evaluated by TUNEL staining in cyst lining epithelia from DBA-positive, Cre-expressing segments. The addition of vitamin E dissipates the increased apoptotic effect of 11beta-dichloro alone. (F) Quantitation of the apoptotic index from (E), three kidneys from three different mice per experimental condition, >1,000 DBA-positive cells were counted. (G) 4-HNE staining of tissues from (A), at P24. The oxidative stress induced by 11beta-dichloro alone (Middle row) is absent in the 11beta-dichloro+vitamin E co-treated kidneys. (Scale bar, 20 µm.) Statistics: N.S., not significant (P > 0.05); *P < 0.05; **P < 0.01; ***P < 0.001 determined by ANOVA. Data are plotted as mean ± SEM.