Dopamine treatment attenuates acute kidney injury in a rat model of deep hypothermia and rewarming: The role of renal H2S-producing enzymes

George J. Dugbartey, Fatemeh Talaei, Martin C. Houwertjes, Maaike Goris, Anne H. Epema, Hjalmar R. Bouma, Robert H. Henning*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

16 Citations (Scopus)

Abstract

Hypothermia and rewarming produces organ injury through the production of reactive oxygen species. We previously found that dopamine prevents hypothermia and rewarming-induced apoptosis in cultured cells through increased expression of the H2S-producing enzyme cystathionine beta-Synthase (CBS). Here, we investigate whether dopamine protects the kidney in deep body cooling and explore the role of H2S-producing enzymes in an in vivo rat model of deep hypothermia and rewarming. In anesthetized Wistar rats, body temperature was decreased to 15 degrees C for 3 h, followed by rewarming for 1 h. Rats (n > 5 per group) were treated throughout the procedure with vehicle or dopamine infusion, and in the presence or absence of a non-specific inhibitor of H2S-producing enzymes, amino-oxyacetic acid (AOAA). Kidney damage and renal expression of three H2S-producing enzymes (CBS, CSE and 3-MST) was quantified and serum H2S level measured. Hypothermia and rewarming induced renal damage, evidenced by increased serum creatinine, renal reactive oxygen species production, KIM-1 expression and influx of immune cells, which was accompanied by substantially lowered renal expression of CBS, CSE, and 3-MST and lowered serum H(2)Slevels. Infusion of dopamine fully attenuated renal damage and maintained expression of H2S-producing enzymes, while normalizing serum H2S. AOAA further decreased the expression of H2S-producing enzymes and serum H2S level, and aggravated renal damage. Hence, dopamine preserves renal integrity during deep hypothermia and rewarming likely by maintaining the expression of renal H2S-producing enzymes and serum H2S. (C) 2015 Elsevier B.V. All rights reserved.

Original languageEnglish
Pages (from-to)225-233
Number of pages9
JournalEuropean Journal of Pharmacology
Volume769
Early online date21-Nov-2015
DOIs
Publication statusPublished - 15-Dec-2015

Keywords

  • Cystathionine beta synthase
  • Dopamine
  • Hypothermia
  • Hydrogen sulfide
  • Acute kidney injury
  • Reactive oxygen species
  • ISCHEMIA-REPERFUSION INJURY
  • HYDROGEN-SULFIDE PROTECTS
  • ISCHEMIA/REPERFUSION-INJURY
  • OXIDATIVE STRESS
  • GRAFT FUNCTION
  • ACCIDENTAL HYPOTHERMIA
  • COLD-PRESERVATION
  • RECEPTOR AGONIST
  • TRANSPLANTATION
  • FAILURE

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