Effect of levosimendan, an inodilator, on streptozotocin-induced diabetic nephropathy in rats

Aly M. Abdelrahman*, Suhail Al Salam, Yousuf Al Suleimani, Mohamed Ashique, Priyadarsini Manoj, Badreldin H. Ali

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


This study examined the effect of levosimendan on streptozotocin-induced early diabetic nephropathy. Rats were distributed into four groups and treated for six weeks. The first and third group received either vehicle or levosimendan (1 mg/kg/day) for the last three weeks, respectively. The second and fourth groups were rendered diabetic by a single intraperitoneal injection of streptozotocin (60 mg/kg) and were treated as the first and third groups, respectively. In the untreated diabetic group, there was a significant decrease in body weight, polyuria and hyperglycemia as well as, increased urinary albumin/creatinine ratio (UACR) and N-acetyl-β-D-glucosaminidase (NAG)/creatinine ratio (UNCR) with no change in creatinine clearance. In addition, diabetes was associated with increased oxidative stress as evidenced by reduced plasma total antioxidant capacity (TAC) and catalase activity and increased plasma malondialdhyde (MDA) and the inflammatory marker, tumor necrosis factor-alpha, (TNF-α). Kidneys from streptozotocin-treated rats showed focal clear renal tubular cells affecting proximal convoluted tubules and mild interstitial fibrosis at the cortico-medullary junction. Levosimendan significantly attenuated the streptozotocin-induced physiological and biochemical changes and there was less clear renal tubular cells. This study shows that levosimendan ameliorated some of the changes seen in streptozotocin-induced early diabetic nephropathy in rats. This could be partly due to its antioxidative and anti-inflammatory effects.

Original languageEnglish
Article number172960
Pages (from-to)172960
JournalEuropean Journal of Pharmacology
Publication statusPublished - Apr 15 2020


  • Animals
  • Antioxidants/metabolism
  • Blood Glucose/metabolism
  • Body Weight/drug effects
  • Cardiotonic Agents/therapeutic use
  • Cytokines/metabolism
  • Diabetes Mellitus, Experimental/complications
  • Diabetic Nephropathies/drug therapy
  • Fibrosis
  • Hyperglycemia/drug therapy
  • Kidney/pathology
  • Male
  • Oxidative Stress/drug effects
  • Polyuria/drug therapy
  • Rats
  • Rats, Sprague-Dawley
  • Simendan/therapeutic use


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