Ghrelin protects mice against endotoxemia-induced acute kidney injury

Wei Wang, Shweta Bansal, Sandor Falk, Danica Ljubanovic, Robert Schrier

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

Acute kidney injury (AKI) in septic patients drastically increases the mortality to 50-80%. Sepsis is characterized by hemodynamic perturbations as well as overwhelming induction of proinflammatory cytokines. Since ghrelin has been shown to have anti-inflammatory properties, we hypothesized that ghrelin may afford renal protection during endotoxemia-induced AKI. Studies were conducted in a normotensive endotoxemia-induced AKI model in mice by intraperitoneal injection of 3.5 mg/kg LPS. Serum ghrelin levels were increased during endotoxemia accompanied by increased ghrelin receptor (GHSR-1a) protein expression in the kidney. Ghrelin administration (1.0 mg/kg sc 6 h and 30 min before and 14 h after LPS) significantly decreased serum cytokine levels (TNF-α, IL-1β, and IL-6) and serum endothelin-1 levels which had been induced by LPS. The elevated serum nitric oxide (NO) levels and renal inducible NO synthase expression were also decreased by ghrelin. Renal TNF-α levels were also increased significantly in response to LPS and ghrelin significantly attenuated this increase. When administrated before LPS, ghrelin protected against the fall in glomerular filtration rate at 16 h (172.9 ± 14.7 vs. 90.6 ± 15.2 μl/min, P < 0.001) and 24 h (147.2 ± 20.3 vs. 59.4 ± 20.7 μl/min, P < 0.05) as well as renal blood flow at 16 h (1.65 ± 0.07 vs. 1.47 ± 0.04 ml/min, P < 0.01) and 24 h (1.56 ± 0.08 vs. 1.22 ± 0.03 ml/min, P < 0.05) after LPS administration without affecting mean arterial pressure. Ghrelin remained renal protective even when it was given after LPS. In summary, ghrelin offered significant protection against endotoxemia-induced AKI. The renal protective effect of ghrelin was associated with an inhibition of the proinflammatory cytokines. Of particular importance was the suppression of TNF-α both in the circulation and kidney tissues. Thus, ghrelin may be a promising peptide in managing endotoxemia-induced AKI.

Original languageEnglish (US)
Pages (from-to)F1032-F1037
JournalAmerican Journal of Physiology - Renal Physiology
Volume297
Issue number4
DOIs
StatePublished - Oct 1 2009
Externally publishedYes

Keywords

  • Proinflammatory cytokines
  • Sepsis

ASJC Scopus subject areas

  • Physiology
  • Urology

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