AJP - Renal Physiology, Vol 248, Issue 3 332-F339, Copyright © 1985 by American Physiological Society
Protective effect of thyroxine but not parathyroidectomy on gentamicin nephrotoxicity
R. E. Cronin and J. A. Newman
Gentamicin nephrotoxicity increases renal cortex calcium and sodium and
decreases renal cortex Na-K-ATPase activity. Human acute renal failure is
accompanied by an increase in parathyroid hormone (PTH), a hormone that
stimulates calcium uptake by tissues, and by a decrease in thyroid hormone,
a hormone that increases renal cortex Na-K-ATPase activity. This study
evaluated the role of extracellular calcium, PTH, and thyroxine in the
pathogenesis of gentamicin nephrotoxicity. Chronically parathyroidectomized
hypocalcemic rats (PTXG) given gentamicin (30 mg/kg s.c. twice daily for 8
days) were not protected from renal failure when compared with intact rats
given gentamicin (NG), serum creatinine being 4.4 +/- 1.0 and 3.7 +/- 0.7
mg/dl, respectively, compared with normals (N), 1.2 +/- 0.1 mg/dl. Rats
given thyroxine (10 micrograms/100 g body wt for 10 days) before and during
gentamicin (PTXT4G) had a serum creatinine not significantly different from
normals, 2.1 +/- 0.4 mg/dl. Plasma T4 was reduced in PTXG, NG, and PTXT4G
compared with N, but the value for PTXT4G was significantly higher than for
either PTXG or NG. Renal cortex Na-K-ATPase activity (mumol Pi X mg prot-1
X h-1) was lower in PTXG (2.3 +/- 0.2) and NG (2.4 +/- 0.5) compared with N
(3.7 +/- 0.1), but activity was not reduced in PTXT4G (3.2 +/- 0.2)
Thyroxine was protective also against gentamicin nephrotoxicity in intact
rats. Clearance and excretion studies indicated that this protection did
not result from an increase in glomerular filtration rate, filtered load of
calcium, or urinary calcium excretion.(ABSTRACT TRUNCATED AT 250 WORDS)
