Protective effect of thyroxine but not parathyroidectomy on gentamicin nephrotoxicity.
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)
Cronin
R E
RE
Newman
J A
JA
D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000517:prevention & control; D000818:Animals; D001835:Body Weight; D002118:Calcium / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D005839:Gentamicins / Q000633:toxicity*; D005919:Glomerular Filtration Rate; D007473:Ion Channels / Q000378:metabolism; D007672:Kidney Cortex / Q000378:metabolism; D008297:Male; D010280:Parathyroid Glands / Q000502:physiology / Q000601:surgery*; D010281:Parathyroid Hormone / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013974:Thyroxine / Q000627:therapeutic use*
D005839:Gentamicins; D007473:Ion Channels; D010281:Parathyroid Hormone; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D013974:Thyroxine; D002118:Calcium