Cathelicidin attenuates hyperoxia-induced kidney injury in newborn rats

Research output: Contribution to journalArticle

Abstract

Aim: Supplemental oxygen is often used to treat neonates with respiratory disorders. Human and animal studies have demonstrated that neonatal hyperoxia increases oxidative stress and induces damage and collagen deposition in kidney during the perinatal period. Cathelicidin LL-37 is one important group of human antimicrobial peptides which exhibits antioxidant activity and its overexpression resists hyperoxia-induced oxidative stress. This study was designed to evaluate the protective effects of cathelicidin in hyperoxia-induced kidney injury in newborn rats. Methods: Sprague-Dawley rat pups were reared in either room air (RA) or hyperoxia (85% O2) and were randomly treated with low-dose (4 mg/kg) and high-dose (8 mg/kg) cathelicidin in normal saline (NS) administered intraperitoneally on postnatal days 1–6. The following six groups were obtained: RA + NS, RA + low-dose cathelicidin, RA + high-dose cathelicidin, O2 + NS, O2 + low-dose cathelicidin, and O2 + high-dose cathelicidin. Kidneys were taken for Western blot and histological analyses on postnatal day 7. Results: The hyperoxia-reared rats exhibited significantly lower body weights and anti-inflammatory M2 macrophages, but the kidney injury scores, oxidative stress marker 8-hydroxy-2'-deoxyguanosine (8-OHdG)-positive cells, pro-inflammatory M1 macrophages, collagen deposition, and NF-κB expression were higher than did the RA-reared rats. Conclusions: Cathelicidin treatment attenuated kidney injury as evidenced by lower kidney injury scores, 8-OHdG-positive cells, collagen deposition, and reversion of hyperoxia-induced M1/M2 macrophage polarization. The role of Cathelicidin in ameliorates kidney injury of the hyperoxia newborn rats was accompanied by decreased NF-κB expression, which probably through the modulating NF-κB activity in the kidney.

Original languageEnglish
Pages (from-to)733-741
Number of pages9
JournalRenal Failure
Volume41
Issue number1
DOIs
Publication statusPublished - Jan 1 2019

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Hyperoxia
Kidney
Wounds and Injuries
Air
Oxidative Stress
Collagen
Macrophages
CAP18 lipopolysaccharide-binding protein
Sprague Dawley Rats
Anti-Inflammatory Agents
Antioxidants
Western Blotting
Body Weight
Oxygen
Peptides

Keywords

  • Antimicrobial peptide
  • collagen
  • inducible nitric oxide synthase
  • nuclear factor-κB
  • oxidative stress
  • Ym-1

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Nephrology

Cite this

Cathelicidin attenuates hyperoxia-induced kidney injury in newborn rats. / Chou, Hsiu Chu; Chen, Chung Ming.

In: Renal Failure, Vol. 41, No. 1, 01.01.2019, p. 733-741.

Research output: Contribution to journalArticle

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abstract = "Aim: Supplemental oxygen is often used to treat neonates with respiratory disorders. Human and animal studies have demonstrated that neonatal hyperoxia increases oxidative stress and induces damage and collagen deposition in kidney during the perinatal period. Cathelicidin LL-37 is one important group of human antimicrobial peptides which exhibits antioxidant activity and its overexpression resists hyperoxia-induced oxidative stress. This study was designed to evaluate the protective effects of cathelicidin in hyperoxia-induced kidney injury in newborn rats. Methods: Sprague-Dawley rat pups were reared in either room air (RA) or hyperoxia (85{\%} O2) and were randomly treated with low-dose (4 mg/kg) and high-dose (8 mg/kg) cathelicidin in normal saline (NS) administered intraperitoneally on postnatal days 1–6. The following six groups were obtained: RA + NS, RA + low-dose cathelicidin, RA + high-dose cathelicidin, O2 + NS, O2 + low-dose cathelicidin, and O2 + high-dose cathelicidin. Kidneys were taken for Western blot and histological analyses on postnatal day 7. Results: The hyperoxia-reared rats exhibited significantly lower body weights and anti-inflammatory M2 macrophages, but the kidney injury scores, oxidative stress marker 8-hydroxy-2'-deoxyguanosine (8-OHdG)-positive cells, pro-inflammatory M1 macrophages, collagen deposition, and NF-κB expression were higher than did the RA-reared rats. Conclusions: Cathelicidin treatment attenuated kidney injury as evidenced by lower kidney injury scores, 8-OHdG-positive cells, collagen deposition, and reversion of hyperoxia-induced M1/M2 macrophage polarization. The role of Cathelicidin in ameliorates kidney injury of the hyperoxia newborn rats was accompanied by decreased NF-κB expression, which probably through the modulating NF-κB activity in the kidney.",
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