Stimulation of carnitine palmitoyltransferase 1 improves renal function and attenuates tissue damage after ischemia/reperfusion

Juan Pablo Idrovo, Weng Lang Yang, Jeffrey Nicastro, Gene F. Coppa, Ping Wang

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Background: Renal injury as a result of ischemia/reperfusion (I/R) is a major clinical problem with a high mortality rate and a lack of therapeutic treatment. During I/R, cellular homeostasis is disrupted owing to energy depletion, leading to cell death. Fatty acid β-oxidation is the major metabolic pathway for generating adenosine triphosphate (ATP) in the kidneys, which is governed by carnitine palmitoyltransferase 1 (CPT1). C75 is a synthetic compound that up-regulates CPT1 activity. Thus, we hypothesized that C75 treatment could increase energy production and alleviate renal I/R injury. Methods: We subjected male adult rats to renal I/R by bilateral renal pedicle clamping with microvascular clips for 60 min, followed by administration of 8% dimethyl sulfoxide (vehicle) or C75 (3 mg/kg body weight), with 5 animals/group. We collected blood and renal tissues 24 h after reperfusion and subjected them to various measurements and histological examination. Results: C75 treatment restored the loss of CPT1 activity and intracellular ATP levels in the kidneys after I/R. Administration of C75 significantly lowered serum creatinine, blood urea nitrogen, aspartate aminotransferase, and lactate dehydrogenase levels elevated by I/R. C75 treatment preserved morphological features of the kidneys with a significant improvement in the damage score. In addition, C75 treatment inhibited the increase of TNF-α levels in serum and kidneys, and lowered myeloperoxidase activity in the kidneys after I/R. Conclusions: Stimulation of CPT1 activity by C75 recovered ATP depletion, improved renal function, attenuated tissue injury, and inhibited proinflammatory cytokine production and neutrophil infiltration after renal I/R injury. Therefore, enhancing the metabolism pathways for energy production may provide a novel modality to treat renal I/R injury.

Original languageEnglish (US)
Pages (from-to)157-164
Number of pages8
JournalJournal of Surgical Research
Volume177
Issue number1
DOIs
StatePublished - Sep 2012
Externally publishedYes

Keywords

  • ATP
  • C75
  • Carnitine palmitoyltransferase 1
  • Inflammation
  • Renal ischemia and reperfusion injury

ASJC Scopus subject areas

  • Surgery

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