Volume 60, Issue 3, Pages 1047-1057 (September 2001) Acute cholestatic liver disease protects against glycerol-induced acute renal failure in the rat  Nelson Leung, Anthony J. Croatt, Jill J. Haggard, Joseph P. Grande, Karl A. Nath  Kidney International  Volume 60, Issue 3, Pages 1047-1057 (September 2001) DOI: 10.1046/j.1523-1755.2001.0600031047.x Copyright © 2001 International Society of Nephrology Terms and Conditions

Figure 1 Effect of ligation of the common bile duct or sham operation on renal function, as measured by the concentration of plasma creatinine prior to and one day following the intramuscular administration of hypertonic glycerol (7.5 mL/kg body weight). Day 0 represents plasma creatinine concentrations just prior to the administration of glycerol (7.5 mL/kg body weight) to rats that, six days previously, were subjected to ligation of the common bile duct (▪) or sham operation (□). Day 1 refers to measurements of plasma creatinine concentration undertaken one day after the injection of intramuscular glycerol (7.5 mL/kg body weight) in these two groups. *P < 0.05 vs. plasma creatinine concentration in rats subjected to sham operation. Kidney International 2001 60, 1047-1057DOI: (10.1046/j.1523-1755.2001.0600031047.x) Copyright © 2001 International Society of Nephrology Terms and Conditions

Figure 2 Representative histologic sections of the kidney stained with hematoxylin and eosin in rats two days after the administration of glycerol (7.5 mL/kg body weight) and that, six days previously, were subjected to either sham operation (A, low power, ×100; B, high power, ×400) or ligation of the common bile duct (C, low power, ×100; and D, high power, ×400). The kidney in sham-operated rats subjected to glycerol-induced acute renal failure demonstrates extensive necrosis of proximal tubules and intratubular cast formation; the distal tubules and glomeruli are relatively well preserved (A and B). In contrast, the kidney in the common bile duct ligated rat subjected to glycerol-induced acute renal failure demonstrates remarkable preservation of histologic integrity with a relative lack of proximal tubular epithelial cell necrosis and intratubular cast formation (C and D). Kidney International 2001 60, 1047-1057DOI: (10.1046/j.1523-1755.2001.0600031047.x) Copyright © 2001 International Society of Nephrology Terms and Conditions

Figure 3 Plasma creatine phosphokinase activity (CK, A), plasma hemoglobin concentrations (B), and plasma lactate dehydrogenase activity (LDH, C) six hours after the intramuscular administration of hypertonic glycerol (7.5 mL/kg body weight) in rats subjected to sham operation (□) or ligation of the common bile duct (▪). *P < 0.05 vs. mean values for this index in rats subjected to sham operation. Kidney International 2001 60, 1047-1057DOI: (10.1046/j.1523-1755.2001.0600031047.x) Copyright © 2001 International Society of Nephrology Terms and Conditions

Figure 4 (A) Heme oxygenase-1 mRNA expression in the kidney in rats subjected to sham operation (SO) or ligation of the common bile duct (BDL). Each lane represents RNA extracted from a single kidney of an individual rat. Provided below the Northern analysis are the standardized, individual, densitometric readings and the mean standardized, densitometric readings. (B) Measurements of kidney heme oxygenase activity in rats subjected to SO or BDL. *P < 0.05 vs. heme oxygenase activity in rats subjected to sham operation (SO). Kidney International 2001 60, 1047-1057DOI: (10.1046/j.1523-1755.2001.0600031047.x) Copyright © 2001 International Society of Nephrology Terms and Conditions

Figure 5 Heme oxygenase-1 mRNA expression in the liver in rats subjected to sham operation (SO) or ligation of the common bile duct (BDL). Each lane represents RNA extracted from a single liver of an individual rat. Provided below the Northern analysis are the standardized, individual, densitometric readings, and the mean standardized, densitometric readings for each group. Kidney International 2001 60, 1047-1057DOI: (10.1046/j.1523-1755.2001.0600031047.x) Copyright © 2001 International Society of Nephrology Terms and Conditions

Figure 6 Plasma creatinine concentrations in rats subjected to sham operation (SO) or ligation of the common bile duct (BDL) 24 hours after the administration of hypertonic glycerol (G, 7.5 mL/kg body weight) and pretreated with either tin protoporphyrin (TP) or vehicle (V), the latter administered 15 hours and 3 hours prior to hypertonic glycerol. *P < 0.05 for these comparisons by analysis of variance. Kidney International 2001 60, 1047-1057DOI: (10.1046/j.1523-1755.2001.0600031047.x) Copyright © 2001 International Society of Nephrology Terms and Conditions

Figure 7 Effect of ligation of the common bile duct or sham operation on renal function as measured by the concentration of plasma creatinine prior to and one day following the intramuscular administration of hypertonic glycerol (10 mL/kg body weight). Day 0 represents plasma creatinine concentrations just prior to the administration of glycerol (10 mL/kg body weight) to rats that, six days previously, were subjected to ligation of the common bile duct (▪) or sham operation (□). Day 1 refers to measurements of plasma creatinine concentration undertaken one day after the injection of intramuscular glycerol (10 mL/kg body weight) in these two groups. *P < 0.05 vs. plasma creatinine concentration in rats subjected to sham operation. Kidney International 2001 60, 1047-1057DOI: (10.1046/j.1523-1755.2001.0600031047.x) Copyright © 2001 International Society of Nephrology Terms and Conditions

Figure 8 Effect of increasing concentrations of bilirubin on cytotoxicity in LLC-PK1 cells induced by exposure to chlorodinitrobenzene (CDNB) and hemoglobin and assessed by the LDH release assay. *P < 0.05 vs. % LDH release in the absence of bilirubin. Kidney International 2001 60, 1047-1057DOI: (10.1046/j.1523-1755.2001.0600031047.x) Copyright © 2001 International Society of Nephrology Terms and Conditions