Captopril and Spironolactone can Attenuate Diabetic Nephropathy in Wistar Rats by Targeting ABCA1 and microRNA-33.


Journal

Current pharmaceutical design
ISSN: 1873-4286
Titre abrégé: Curr Pharm Des
Pays: United Arab Emirates
ID NLM: 9602487

Informations de publication

Date de publication:
2022
Historique:
received: 16 11 2021
accepted: 24 02 2022
pubmed: 4 4 2022
medline: 19 8 2022
entrez: 3 4 2022
Statut: ppublish

Résumé

Nephropathy diabetes is one of the important causes of death and a more prevalent cause of end-stage renal disease. The present study investigated the effect of applying spironolactone and captopril and their combination on some renal performance indices and cholesterol-efflux-related gene expression in nephropathy diabetic rats. Intraperitoneal injection of streptozotocin was used to induce diabetes in rats. FBS, creatinine, and BUN were assayed using the calorimetry technique; also, urine microalbumin was assayed by ELISA. Hepatic gene expressions of ABCA1, ABCG1, and miR-33 were evaluated by the real-time PCR method. FBS levels in the captopril-treated group were significantly decreased compared with the untreated diabetic group. BUN levels of treated groups with captopril and a combination of captopril + spironolactone were significantly increased. GFR of both treated diabetic groups with captopril and spironolactone was significantly lower than an untreated diabetic group. ABCA1 gene expression in hepatic cells of the combination of spironolactone + captopril treated group was significantly increased compared to other treated and untreated diabetic groups. The hepatic expression of the ABCG1 gene in the treated and untreated diabetic groups was significantly lower than in the control group. Treatment of the diabetic group with only combination therapy decreased the hepatic gene expression of miR-33 significantly. Obtained results suggest that S+C combination therapy can improve nephropathy and diabetes disorders by targeting the ABCA1 and miR-33 gene expression. It is suggested that miR-33 and ABCA1 genes evaluation could be a new therapeutic strategy for nephropathy diabetes remediation.

Sections du résumé

BACKGROUND
Nephropathy diabetes is one of the important causes of death and a more prevalent cause of end-stage renal disease.
OBJECTIVE
The present study investigated the effect of applying spironolactone and captopril and their combination on some renal performance indices and cholesterol-efflux-related gene expression in nephropathy diabetic rats.
METHODS
Intraperitoneal injection of streptozotocin was used to induce diabetes in rats. FBS, creatinine, and BUN were assayed using the calorimetry technique; also, urine microalbumin was assayed by ELISA. Hepatic gene expressions of ABCA1, ABCG1, and miR-33 were evaluated by the real-time PCR method.
RESULTS
FBS levels in the captopril-treated group were significantly decreased compared with the untreated diabetic group. BUN levels of treated groups with captopril and a combination of captopril + spironolactone were significantly increased. GFR of both treated diabetic groups with captopril and spironolactone was significantly lower than an untreated diabetic group. ABCA1 gene expression in hepatic cells of the combination of spironolactone + captopril treated group was significantly increased compared to other treated and untreated diabetic groups. The hepatic expression of the ABCG1 gene in the treated and untreated diabetic groups was significantly lower than in the control group. Treatment of the diabetic group with only combination therapy decreased the hepatic gene expression of miR-33 significantly.
CONCLUSION
Obtained results suggest that S+C combination therapy can improve nephropathy and diabetes disorders by targeting the ABCA1 and miR-33 gene expression. It is suggested that miR-33 and ABCA1 genes evaluation could be a new therapeutic strategy for nephropathy diabetes remediation.

Identifiants

pubmed: 35366766
pii: CPD-EPUB-122165
doi: 10.2174/1381612828666220401143249
doi:

Substances chimiques

ABCA1 protein, rat 0
ATP Binding Cassette Transporter 1 0
MIRN33 microRNA, rat 0
MicroRNAs 0
Spironolactone 27O7W4T232
Captopril 9G64RSX1XD

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1367-1372

Informations de copyright

Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.

Auteurs

Tina Ghaffari (T)

Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Nariman Moradi (N)

Department of Clinical Biochemistry, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.

Elham Chamani (E)

Department of Clinical Biochemistry, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran.

Zahra Ebadi (Z)

Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Reza Fadaei (R)

Sleep Disorders Research Center, Research Institute for Health, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Shahin Alizadeh-Fanalou (S)

Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Nephrology and Kidney Transplant Research Center, Clinical Research Institute, Urmia University of Medical Sciences, Urmia, Iran.

Sahar Yarahmadi (S)

Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Soudabeh Fallah (S)

Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.

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Classifications MeSH