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

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• 作者：George J. Dugbartey^a ; Fatemeh Talaei^a ; Martin C. Houwertjes^b ; Maaike Goris^a ; Anne H. Epema^b ; Hjalmar R. Bouma^a ; Robert H. Henning^a ; ^{r.h.henning@umcg.nl" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Dopamine (PubChem CID ; 65340) ; Aminooxyacetic acid (PubChem CID ; 286)
• 刊名：European Journal of Pharmacology
• 出版年：2015
• 出版时间：15 December 2015
• 年：2015
• 卷：769
• 期：Complete
• 页码：225-233
• 全文大小：5173 K

文摘

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 β-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 °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 H₂S levels. 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.