Protection by thyroxine in nephrotoxic acute renal failure

Abstract

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-thyroxine (10 micrograms/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 less than 0.025) and group UN (0.52 +/- 0.03 to 1.64 +/- 0.13 mg/dl, P less than 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 less than 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 micron X mg protein-1 X h-1, P less than 0.005) and group CT4 (16.3 +/- 0.6 micron X mg protein-1 X h-1, P less than 0.001) when compared with controls (11.7 +/- 0.5 micron X mg protein-1 X h-1). Na-K-ATPase activity fell in group UN to 10.0 +/- 0.6 micron X mg protein-1 X h-1 (P less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Thyroxine on Hyperkalemia and Renal Cortical Na(+), K(+) - ATPase Activity Induced by Cyclosporin A

“…The demonstration by Suzuki et al (6) of the relief of histologic damage and hyperkalemia by glucocorticoid treatment suggests that the mechanism involves stimulation of renal tubular Na + , K + -ATPase and gives support to the hypothesis that the adverse effects of CsA are indeed the result of a decrease in the activity of this enzyme. In our study of CsA-induced nephrotoxicity and its prevention, we used thyroxine, which is more effective than glucocorticoids in preventing many kinds of renal toxicity (10)(11)(12)(13)(14). Accurate measurement of Na + , K + -ATPase activity in the mi-crosomal fraction is time-consuming and demanding, so we also used a histochemical approach for the measurement of the enzyme activity.…”

“…But recently, Suzuki et al (6) reported that prolonged use of CsA suppresses DNA and RNA synthesis, as well as Na Thyroxine administration has shown protective effects in several experimental models of acute renal failure induced by various and numerous nephrotoxic agents. These effects have been associated with a rise of Na + , K + -ATPase activity in the basolateral membranes of renal tubules (10)(11)(12)(13)(14).…”

Pathogenesis of Acute Renal Failure: New Aspects

“…Bock: Most of these patients probably belong to the cat egory called 'euthyroid sick' syndrome [86], i.e., they are not truly hypothyroid. There are two or three papers describing the prophylactic value of L-thyroxine in ARF [87][88][89], Like several other maneuvers experimentally shown to be of some prophylactic use. thyroxine adminis tration has not been generally adopted for clinical use, probably because the reported benefits were relatively small.…”

The Behavior and Chemical Toxicity of U in the Kidney

“…Gentamicin may cause selective loss of alkaline phosphatase from the brush-border membrane due to its interference with PhI, which is required for attachment of alkaline phosphatase to membranes (Knauss et al 1983). The potential roles of alkaline phosphatase and PhI in U nephrotoxicity are not understood, but Cronin et al (1986) suggested that protection against U-induced acute renal failure afforded by thyroxine in rats was due to a thyroxine-induced reduction of alkaline phosphatase or PhI activity and a significantly elevated activity of renal cortex Na-K-ATPase, which might be inhibited by U (Nechay et al 1980;Kramer et al 1986). Such protection by thyroxine was observed at moderate dosage (0.5 mg U nitrate kg-') but not at high dosage (10 mg U nitrate kg-').…”