Endothelin-1–Mediated Alteration of Metallothionein and Trace Metals in the Liver and Kidneys of Chronically Diabetic Rats
Autor: | Lu Cai, Terry Evans, Subrata Chakrabarti, M. George Cherian, Shali Chen |
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Jazyk: | angličtina |
Rok vydání: | 2002 |
Předmět: |
Endothelin Receptor Antagonists
Male medicine.medical_specialty Endocrinology Diabetes and Metabolism Iron Kidney Diabetes Mellitus Experimental Rats Sprague-Dawley chemistry.chemical_compound Endocrinology Internal medicine Diabetes mellitus medicine Metallothionein Animals Tissue Distribution RNA Messenger Creatinine Sulfonamides Endothelin-1 Kidney metabolism Bosentan Streptozotocin medicine.disease Endothelin 1 Rats Trace Elements Zinc medicine.anatomical_structure chemistry Liver Chronic Disease Copper medicine.drug Research Article |
Zdroj: | International journal of experimental diabetes research |
ISSN: | 1560-4284 |
Popis: | In the present study, the role of endothelin-1 (ET-1) on alterations of hepatic and renal metallothionein (MT) and trace metals (Zn, Cu, and Fe) were investigated in streptozotocin (STZ)- induced diabetic rats. Diabetic rats, age- and sex-matched controls, as well as control and diabetic animals on a dualETA/ETBreceptor blocker, bosentan, were investigated after 6 months of follow-up. MT was measured by cadmium-heme assay. Metals were measured by atomic absorption spectrometer. ET-1 mRNA was analyzed by reverse transcriptase–polymerase chain reaction (RT-PCR) technique. Hepatic and renal ET-1 mRNA was increased in diabetic rats as compared to control rats, along with an increase in both hepatic and renal MT proteins. The increased hepatic MT protein level was associated with decreases in hepatic Cu and Fe, whereas increased renal MT was associated with increases in renal Cu and Fe accumulation. Zn levels were unaltered in both organs in diabetic rats. Bosentan treatment partially prevented the increase in MT levels in both liver and kidney, along with reduced serum creatinine and increased urinary creatinine levels. Further bosentan treatment corrected the increased Cu and Fe levels in the kidney in diabetic rats, but reduced hepatic Cu and Fe levels. No significant effects of bosentan treatment on nondiabetic rats were observed. The data suggest that the possible effects of ET antagonism in diabetes may be mediated via changes in MT and trace metals. |
Databáze: | OpenAIRE |
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