Modulation of renal EGF in dichromate-induced acute renal failure treated with thyroid hormone.
Administration of either thyroid hormone or epidermal growth factor (EGF) ameliorates injury in a variety of experimental acute renal failure (ARF) models. Since thyroid hormone augments EGF release and EGF receptor expression, a hypothesis suggesting that the mechanism of thyroid action is via EGF appears attractive. The present study is an attempt to evaluate the role of EGF in thyroid mediated protection from ARF induced in rats by dichromate. Renal parenchymal levels of acid extractable endogenous EGF were measured by RIA in dichromate exposed, otherwise untreated animals and in those receiving dichromate followed by thyroid. In the untreated case serum creatinine peaked at 2.5 mg % on the third day following dichromate exposure. Endogenous levels of EGF closely paralleled serum creatinine with a six-fold increase observed at peak injury. The source of EGF increase appeared to be a membrane bound precursor as soluble levels of EGF rose in injured kidneys at the expense of Triton-X-100 extractable, immunoreactive material that upon treatment with trypsin yielded additional EGF. T3 administered one hour following dichromate resulted in significant functional protection (peak injury serum creatinines 2.63 +/- 0.76 control vs. 0.98 +/- 0.14 with T3) as well as an approximate doubling in renal EGF levels at 24, 48 and 72 hours (4.7 +/- 0.3 vs. 9.7 +/- 0.8 at 24 hr, 33.5 +/- 6.5 vs. 63.2 +/- 20.0 at 48 hr, and 23.1 +/- 10.0 vs. 44.1 +/- 8.7 ng/g wet weight at 72 hr). There was no beneficial effect of exogenous EGF on renal function either when given in conjunction with T3 or when used alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Seiken
G
G
Department of Nephrology, Walter Reed Army Institute of Research, Washington, D.C.
Grillo
F G
FG
Schaudies
R P
RP
Johnson
J P
JP
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D000818:Animals; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D008297:Male; D011192:Potassium Dichromate; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D013961:Thyroid Gland / Q000502:physiology*; D014284:Triiodothyronine / Q000494:pharmacology*
D011994:Recombinant Proteins; D014284:Triiodothyronine; D004815:Epidermal Growth Factor; D003404:Creatinine; D011192:Potassium Dichromate