engleski

ENDOGENOUS DIGITALIS-LIKE FACTORS AND ENDOTHELIN-1 DURING EXPERIMENTAL TOXIC NEPHOPATHY

Introduction: The purpose of this study was to determine the concentrations of endogenous digitalis-like factors (EDLFs) and endothelins (ETs) in nephropaty induced by Ochratoxin A (OTA). OTA is a nephrotoxic, hepatotoxic and genotoxic micotoxin. The presence of a highly conserved Na,K-ATPase binding domain for cardiac glycoside drugs implies the existence of natural ligands that act as endogenous modulators of enzyme activity. ETs affect several aspects of renal function, including vasoconstriction, regulation of tubule function, cellular proliferation, matrix production and inhibition of Na,K-ATPase. Endothelin-1 (ET-1) is a most potent vasoconstrictor. Alteration of Na,K-ATP-ase activity by inhibitors may play a key role in many fundamental physiological processes. Pathological conditions in animals and humans involving salt and water homeostasis have been associated with alteration of Na,K-ATPase activity and/or the presence of endogenous inhibitors. Results: OTA treatment caused the increase of concentrations of EDLFs: 4.4 ng EDLFs/g kidney tissue, 6.9ng/g and 6.4ng/g in 10, 30 and 60 days treated rats, respectively. In control animals EDLFs were not detectable. Urine ET-1 concentrations (fmol ET-1/mmol creatinine) were not changed significantly. The catalytic activity of Na, K-ATPase increased significantly (26% and 29%) after 30 and 60 days, recpectively. Biochemical parameters of renal functional status were not changed significantly. Conclusion: We conclude that OTA in the doses of 120 mg/kg body weight/day during 30 and 60 days, produced changes in kidney cortex, characterised by increase of concentrations of EDLFs and the higher activity of Na,K-ATPase. However, the standard biochemical parameters for renal tubular function were not changes. The observed increase of the Na,K-ATPase activity might be considered by the presence of EDLFs in kidney tissue, suggesting the activation of the compensatory mechanisms, such as increased synthesis of this enzyme in kidney cortex.

endogenous digitalis-like factors; endothelin-1; nephropathy

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