Thyroxine (T4) protects against ischemic and nephrotoxic experimental acute renal failure (ARF). This study examined functional, biochemical, and morphological markers of uranyl nitrate (UN)-induced renal injury in the rat to determine the cellular site at which T4 exerts its protective effect. In experimental group UNT4, 1-thyroxin (10 μg/100 g body wt) was given for 10 days prior to and for 4 days following a single subcutaneous injection of UN (0.5 mg/kg body wt). Group UN received only UN, and group CT4 received only T4 for 14 days. Five days after UN administration, plasma creatinine rose from base line in group UNT4 (0.52 ± 0.30 to 0.84 ± 0.08 mg/dl, P < 0.025) and group UN (0.52 ± 0.03 to 1.64 ± 0.13 mg/dl, P < 0.001) but not in group CT4 (0.47 ± 0.02 to 0.48 ± 0.04 mg/dl, NS). However, plasma creatinine in group UNT4 was significantly lower than group UN (0.84 ± 0.08 vs. 1.64 ± 0.13 mg/dl, P < 0.001). T4 administration stimulated the basolateral membrane-bound enzyme Na-K-ATPase in the renal cortex homogenate in group UNT4 (13.9 ± 0.5 μm·mg protein-1·h-1, P < 0.005) and group CT4 (16.3 ± 0.6 μm·mg protein-1·h-1, P < 0.001) when compared with controls (11.7 ± 0.5 μm·mg protein-1·h-1). Na-K-ATPase activity fell in group UN to 10.0 ± 0.6 μm·mg protein-1·h-1 (p < 0.025). In groups UNT4 and CT4, the renal cortex homogenate activity of the brush-border enzyme alkaline phosphatase was significantly reduced compared with controls. Morphological studies of the affected renal cortex demonstrated that UN injured a similar number of renal tubular cells in groups UNT4 and UN, but the number of necrotic cells in group UNT4 was less (29.8 ± 2.3 vs. 47.0 ± 5.9%, P < 0.025) and regenerating cells were more plentiful (49.2 ± 3.0 vs. 34.6 ± 3.5%, P < 0.02). These results suggest that T4 mediates protection against ARF at the plasma membrane level. Factors possibly involved in protection are a stimulation of Na-K-ATPase, and alteration in brush-border structure, and an accelerated rate of cellular repair.
|Original language||English (US)|
|Title of host publication||American Journal of Physiology - Renal Fluid and Electrolyte Physiology|
|State||Published - 1986|
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