TY - JOUR
T1 - Effect of levosimendan, an inodilator, on streptozotocin-induced diabetic nephropathy in rats
AU - Abdelrahman, Aly M.
AU - Al Salam, Suhail
AU - Al Suleimani, Yousuf
AU - Ashique, Mohamed
AU - Manoj, Priyadarsini
AU - Ali, Badreldin H.
N1 - Funding Information:
Supported by a grant from Sultan Qaboos University IG/MED/PHAR/18/01 .
Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/4/15
Y1 - 2020/4/15
N2 - 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.
AB - 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.
KW - Antioxidants
KW - Diabetes
KW - Inodilator
KW - Levosimendan
KW - Nephropathy
KW - Streptozotocin
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U2 - 10.1016/j.ejphar.2020.172960
DO - 10.1016/j.ejphar.2020.172960
M3 - Article
C2 - 32001219
AN - SCOPUS:85078991814
SN - 0014-2999
VL - 873
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
M1 - 172960
ER -