DHEA supplementation to dexamethasone-treated rabbits alleviates oxidative stress in kidney-cortex and attenuates albuminuria
| Autor: | Michal Usarek, Joanna Sitek, Katarzyna Winiarska, Anna Kiersztan, Aleksandra Tempes, Paweł Nalepa, Nina Trojan |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Endocrinology Diabetes and Metabolism Clinical Biochemistry Glutathione reductase Dehydroepiandrosterone Kidney medicine.disease_cause Biochemistry Antioxidants Dexamethasone Superoxide dismutase 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Endocrinology Malondialdehyde Internal medicine medicine Albuminuria Animals Glucocorticoids Molecular Biology Glutathione Transferase chemistry.chemical_classification biology Glutathione peroxidase Cell Biology Glutathione Oxidative Stress 030104 developmental biology chemistry 030220 oncology & carcinogenesis biology.protein Molecular Medicine Rabbits medicine.symptom Oxidoreductases hormones hormone substitutes and hormone antagonists Oxidative stress |
| Zdroj: | The Journal of Steroid Biochemistry and Molecular Biology. 174:17-26 |
| ISSN: | 0960-0760 |
| Popis: | Our recent study has shown that dehydroepiandrosterone (DHEA) administered to rabbits partially ameliorated several dexamethasone (dexP) effects on hepatic and renal gluconeogenesis, insulin resistance and plasma lipid disorders. In the current investigation, we present the data on DHEA protective action against dexP-induced oxidative stress and albuminuria in rabbits. Four groups of adult male rabbits were used in the in vivo experiment: (1) control, (2) dexP-treated, (3) DHEA-treated and (4) both dexP- and DHEA-treated. Administration of dexP resulted in accelerated generation of renal hydroxyl free radicals (HFR) and malondialdehyde (MDA), accompanied by diminished superoxide dismutase (SOD) and catalase activities and a dramatic rise in urinary albumin/creatinine ratio. Treatment with DHEA markedly reduced dexP-induced oxidative stress in kidney-cortex due to a decline in NADPH oxidase activity and enhancement of catalase activity. Moreover, DHEA effectively attenuated dexP-evoked albuminuria. Surprisingly, dexP-treated rabbits exhibited elevation of GSH/GSSG ratio, accompanied by a decrease in glutathione peroxidase (GPx) and glutathione-S-transferase (GST) activities as well as an increase in glucose-6-phosphate dehydrogenase (G6PDH) activity. Treatment with DHEA resulted in a decline in GSH/GSSG ratio and glutathione reductase (GR) activity, accompanied by an elevation of GPx activity. Interestingly, rabbits treated with both dexP and DHEA remained the control values of GSH/GSSG ratio. As the co-administration of DHEA with dexP resulted in (i) reduction of oxidative stress in kidney-cortex, (ii) attenuation of albuminuria and (iii) normalization of glutathione redox state, DHEA might limit several undesirable renal side effects during chronic GC treatment of patients suffering from allergies, asthma, rheumatoid arthritis and lupus. Moreover, its supplementation might be particularly beneficial for the therapy of patients with glucocorticoid-induced diabetes. |
| Databáze: | OpenAIRE |
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