Analysis of proximal tubule injury upon lithium treatment.

12-week old female BTBR-WT and -ob/ob mice received standard chow or chow with lithium supplementation (10 or 40 LiCl/kg) for 12 weeks. Kidney lysates were used to immunoblot for megalin (A) and cubilin (B) abundance, as shown by representative images in the upper panels, and subsequent densitometric analysis in lower panels (n = 9/group). Arrows indicate the 600-kDa bands for megalin and 460-kDa band for cubilin. Spot urine, collected in the week before sacrifice, was used to determine NAG activity (C) and NGAL (D) levels. Kidney sections were stained with PAS to determine brush border damage in the different groups, as is shown in the representative pictures (E). The scale bar represents 50 μM. The presence of brush border damage was scored as follows: 0) none, 1) minimal, 2) mild, 3) moderate and 4) severe (F). *p<0.05; ***p<0.001. Cm, Coomassie.