Effect of levosimendan, a calcium sensitizer, on cisplatin-induced nephrotoxicity in rats

Aly Abdelrahman, Yousuf Al Suleimani, Asem Shalaby, Mohammed Ashique, Priyadarsini Manoj, Hasna Al-Saadi, Badreldin Ali

Research output: Contribution to journalArticle

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Abstract

We investigated the effect of levosimendan on cisplatin (Cis)-induced nephrotoxicity. Rats were divided into four groups (n = 6). The first and second groups received normal saline (control) and intraperitoneal (i.p.) cisplatin (6 mg/kg) on day 7, respectively. The third and fourth groups received a single intraperitoneal (i.p.) injection of Cis on day 7 and levosimendan (1 mg/kg/day, orally) or vehicle for 10 days, respectively. At day 11, animals were anaesthetized and blood collected and kidneys removed. Another four groups were treated the same as the previous four groups to measure renal blood flow. Cis induced nephrotoxicity as evidenced by biochemical, histopathological and hemodynamic changes. Levosimendan partially reduced Cis-induced increase in plasma urea, creatinine and neutrophil gelatinase-associated lipocalin (NGAL) levels and decrease in creatinine clearance. Levosimendan partially reduced Cis-induced increase in urinary albumin/creatinine ratio, N-Acetyl-β-D-Glucosaminidase (NAG) and kidney Injury Molecule-1 (KIM-1). Levosimendan significantly attenuated the effect of Cis on plasma concentration of plasma tumor necrosis factor–alpha (TNF-α), antioxidant indices [catalase and superoxide dismutase (SOD)] and lipid peroxidation. Cis induced acute tubular necrosis with tubular dilatation, interstitial edema and congestion. Levosimendan attenuated the remarkable renal damage and reduced renal blood flow induced by Cis. In conclusion this study shows that levosimendan has a partial protective effect on Cis-induced nephrotoxicity. The protective effect of levosimendan is shown to be related to its anti-inflammatory, antioxidant and vasodilator effects.

Original languageEnglish
Pages (from-to)232-238
Number of pages7
JournalToxicology Reports
Volume6
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Cisplatin
Rats
Calcium
Creatinine
Blood
Renal Circulation
Kidney
Plasmas
Necrosis
Antioxidants
simendan
Lipocalins
Hexosaminidases
Gelatinases
Hemodynamics
Intraperitoneal Injections
Vasodilator Agents
Catalase
Lipid Peroxidation
Superoxide Dismutase

Keywords

  • Anti-inflammatory
  • Cisplatin
  • Inodilator
  • Levosimendan
  • Nephrotoxicity

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Effect of levosimendan, a calcium sensitizer, on cisplatin-induced nephrotoxicity in rats. / Abdelrahman, Aly; Al Suleimani, Yousuf; Shalaby, Asem; Ashique, Mohammed; Manoj, Priyadarsini; Al-Saadi, Hasna; Ali, Badreldin.

In: Toxicology Reports, Vol. 6, 01.01.2019, p. 232-238.

Research output: Contribution to journalArticle

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AB - We investigated the effect of levosimendan on cisplatin (Cis)-induced nephrotoxicity. Rats were divided into four groups (n = 6). The first and second groups received normal saline (control) and intraperitoneal (i.p.) cisplatin (6 mg/kg) on day 7, respectively. The third and fourth groups received a single intraperitoneal (i.p.) injection of Cis on day 7 and levosimendan (1 mg/kg/day, orally) or vehicle for 10 days, respectively. At day 11, animals were anaesthetized and blood collected and kidneys removed. Another four groups were treated the same as the previous four groups to measure renal blood flow. Cis induced nephrotoxicity as evidenced by biochemical, histopathological and hemodynamic changes. Levosimendan partially reduced Cis-induced increase in plasma urea, creatinine and neutrophil gelatinase-associated lipocalin (NGAL) levels and decrease in creatinine clearance. Levosimendan partially reduced Cis-induced increase in urinary albumin/creatinine ratio, N-Acetyl-β-D-Glucosaminidase (NAG) and kidney Injury Molecule-1 (KIM-1). Levosimendan significantly attenuated the effect of Cis on plasma concentration of plasma tumor necrosis factor–alpha (TNF-α), antioxidant indices [catalase and superoxide dismutase (SOD)] and lipid peroxidation. Cis induced acute tubular necrosis with tubular dilatation, interstitial edema and congestion. Levosimendan attenuated the remarkable renal damage and reduced renal blood flow induced by Cis. In conclusion this study shows that levosimendan has a partial protective effect on Cis-induced nephrotoxicity. The protective effect of levosimendan is shown to be related to its anti-inflammatory, antioxidant and vasodilator effects.

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