Modulation of renal EGF in dichromate-induced acute renal failure treated with thyroid hormone

Abstract

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)

Protective effect of SnCl2 on K2Cr2O7-induced nephrotoxicity in rats: The indispensability of HO-1 preinduction and lack of association with some antioxidant enzymes

“…Occupational exposure to chromium has been associated with welders, chrome-plating workers, and chromium pigment factories workers (Verschoor et al, 1988). Chromium is known to cause allergic dermatitis (Ingber et al, 1988), carcinogenicity (Norseth, 1986), and ARF in humans (Picaud et al, 1991;Sharma et al, 1978;Verschoor et al, 1988) and in animals (Michael et al, 1991;Pedraza-Chaverri et al, 1995b;Seiken et al, 1994). ROS has been involved in the pathophysiology of ARF induced by K 2 Cr 2 O 7 and some antioxidants are able to ameliorate renal damage induced by this compound (Appenroth and Winnefeld, 1998;Barrera et al, 2003;Huang et al, 1999;Na et al, 1992;Sengupta et al, 1992).…”

“…ARF induced by potassium dichromate (K 2 Cr 2 O 7 ) has been used as a model to study the pathophysiology of this disease (Pedraza-Chaverri et al, 1995b;Seiken et al, 1994). Experimental data show that chromate affects selectively the convoluted section of the proximal tubules (Berry et al, 1978;Evan and Dail, 1974;Franchini et al, 1978;Pedraza-Chaverri et al, 1995b) and induces acute necrosis of renal tubules (Franchini et al, 1978).…”

Time course study of oxidative and nitrosative stress and antioxidant enzymes in K2Cr2O7-induced nephrotoxicity

“…Acute renal failure (ARF) induced by potassium dichromate (K 2 Cr 2 O 7 ) has been used as a model to study the pathophysiology of this disease [7,9]. Experimental data show that chromate affects selectively the convoluted section of the proximal tubules [7,12-15] and induces acute necrosis of renal tubules [14,15].…”

Glycated plasma proteins in experimentally induced acute toxic renal failure by dichromate injection: evidence for loss with urine and decreased plasma levels.

“…Indeed, hexavalent chromium [Cr(VI)] has been shown to be a proximal tubular nephrotoxic (Hayes 1982;Na et al 1992;Seiken et al 1994). Indeed, hexavalent chromium [Cr(VI)] has been shown to be a proximal tubular nephrotoxic (Hayes 1982;Na et al 1992;Seiken et al 1994).…”

“…Histology shows that sodium dichromate injection causes dramatic acute tubular injury in the proximal convolute tubule, compatible with diagnosis of toxic acute tubular necrosis. Indeed, hexavalent chromium [Cr(VI)] has been shown to be a proximal tubular nephrotoxic (Hayes 1982;Na et al 1992;Seiken et al 1994). Acute poisoning with dichromate causes renal failure with tubular necrosis in man (Brenner & Lazarus 1983).…”