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Combination therapy with spironolactone and candesartan protects against streptozotocin-induced diabetic nephropathy in rats.
Eur J Pharmacol. 2014 Dec 05; 744:173-82.EJ

Abstract

Diabetic nephropathy is one of the most common causes of end-stage kidney disease. Aldosterone and angiotensin II appear to play a crucial role in the pathogenesis of this disease. The present study aimed to investigate effects of the combination therapy with spironolactone and candesartan on diabetic nephropathy and elucidate the underlying mechanism(s) involved. Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin (STZ) (55 mg/kg). The diabetic rats were orally treated with spironolactone (50 mg/kg/day) and/or candesartan (1 mg/kg/day) for 8 weeks. Administration of STZ caused a marked elevation in the serum level of creatinine, urea and urinary albumin-creatinine ratio (ACR). This was associated with upregulated renal protein levels of nuclear factor-kappa B (NF-κB), transforming growth factor (TGF)-β, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) alongside increasing the renal superoxide anion (O2(-)) production, malondialdehyde (MDA) level and the systolic blood pressure. There was a marked decrease in nitric oxide (NO) bioavailability and antioxidant enzyme capacity. The combined therapy of spironolactone and candesartan significantly normalized the oxidative stress and fibrotic/inflammatory alterations. Additionally, the elevated blood pressure was attenuated by administration of candesartan alone or in combination. This was associated with improving the renal function parameters. The combined therapy exhibited more profound response compared to the monotherapy. In conclusion, our results demonstrate that the combined therapy of spironolactone and candesartan can confer an additive benefit over the use of either drug alone against STZ-induced diabetic nephropathy, presumably via attenuating the inflammatory responses and oxidative status markers.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, 61511 Minia, Egypt. Electronic address: amal_arwa1@yahoo.com.Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, 61511 Minia, Egypt; Department of Pharmacology and Toxicology, Ibn Sina National College for Medical Studies, Jeddah, Saudi Arabia.Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, 61511 Minia, Egypt.Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, 61511 Minia, Egypt.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25446917

Citation

Hofni, Amal, et al. "Combination Therapy With Spironolactone and Candesartan Protects Against Streptozotocin-induced Diabetic Nephropathy in Rats." European Journal of Pharmacology, vol. 744, 2014, pp. 173-82.
Hofni A, El-Moselhy MA, Taye A, et al. Combination therapy with spironolactone and candesartan protects against streptozotocin-induced diabetic nephropathy in rats. Eur J Pharmacol. 2014;744:173-82.
Hofni, A., El-Moselhy, M. A., Taye, A., & Khalifa, M. M. (2014). Combination therapy with spironolactone and candesartan protects against streptozotocin-induced diabetic nephropathy in rats. European Journal of Pharmacology, 744, 173-82. https://doi.org/10.1016/j.ejphar.2014.10.021
Hofni A, et al. Combination Therapy With Spironolactone and Candesartan Protects Against Streptozotocin-induced Diabetic Nephropathy in Rats. Eur J Pharmacol. 2014 Dec 5;744:173-82. PubMed PMID: 25446917.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Combination therapy with spironolactone and candesartan protects against streptozotocin-induced diabetic nephropathy in rats. AU - Hofni,Amal, AU - El-Moselhy,Mohamed A, AU - Taye,Ashraf, AU - Khalifa,Mohamed M, Y1 - 2014/10/27/ PY - 2014/07/05/received PY - 2014/10/05/revised PY - 2014/10/08/accepted PY - 2014/12/3/entrez PY - 2014/12/3/pubmed PY - 2015/8/8/medline KW - Candesartan KW - Diabetic nephropathy KW - Oxidative stress KW - Spironolactone SP - 173 EP - 82 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 744 N2 - Diabetic nephropathy is one of the most common causes of end-stage kidney disease. Aldosterone and angiotensin II appear to play a crucial role in the pathogenesis of this disease. The present study aimed to investigate effects of the combination therapy with spironolactone and candesartan on diabetic nephropathy and elucidate the underlying mechanism(s) involved. Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin (STZ) (55 mg/kg). The diabetic rats were orally treated with spironolactone (50 mg/kg/day) and/or candesartan (1 mg/kg/day) for 8 weeks. Administration of STZ caused a marked elevation in the serum level of creatinine, urea and urinary albumin-creatinine ratio (ACR). This was associated with upregulated renal protein levels of nuclear factor-kappa B (NF-κB), transforming growth factor (TGF)-β, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) alongside increasing the renal superoxide anion (O2(-)) production, malondialdehyde (MDA) level and the systolic blood pressure. There was a marked decrease in nitric oxide (NO) bioavailability and antioxidant enzyme capacity. The combined therapy of spironolactone and candesartan significantly normalized the oxidative stress and fibrotic/inflammatory alterations. Additionally, the elevated blood pressure was attenuated by administration of candesartan alone or in combination. This was associated with improving the renal function parameters. The combined therapy exhibited more profound response compared to the monotherapy. In conclusion, our results demonstrate that the combined therapy of spironolactone and candesartan can confer an additive benefit over the use of either drug alone against STZ-induced diabetic nephropathy, presumably via attenuating the inflammatory responses and oxidative status markers. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/25446917/Combination_therapy_with_spironolactone_and_candesartan_protects_against_streptozotocin_induced_diabetic_nephropathy_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(14)00728-6 DB - PRIME DP - Unbound Medicine ER -