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骨骼肌、心脏和肝脏是口服亚硝酸盐治疗后一氧化氮代谢产物积累的主要器官。

The Skeletal Muscle, the Heart, and the Liver Are the Major Organs of the Accumulation of Nitric Oxide Metabolites after Oral Nitrite Treatment.

作者信息

Lima-Silva Ana K, Rebelo Macario A, Barros Alessandra C, Conde-Tella Sandra O, Tanus-Santos Jose E

机构信息

Department of Pharmacology, Ribeirao Preto Medical School, University of São Paulo, Ribeirão Preto 14040-900, Brazil.

Department of Pharmacology, State University of Campinas, Campinas 13083-855, Brazil.

出版信息

Antioxidants (Basel). 2024 Feb 20;13(3):255. doi: 10.3390/antiox13030255.

Abstract

Nitrite is a nitric oxide (NO) metabolite, which may be bioactivated to generate NO in vivo and supplement endogenous NO formation, especially in cardiovascular and metabolic diseases. However, it is not known whether treatment with oral nitrite results in the accumulation of NO metabolites in different organs. Moreover, treatment with omeprazole, an inhibitor of gastric acid secretion, severely affects the gastric formation of S-nitrosothiols induced with oral nitrite treatment. However, no previous study has examined whether omeprazole affects the nitrite-induced accumulation of NO metabolites in different organs. This study examined in rats the effects of oral sodium nitrite treatment (15 mg/kg via gavage for 1 or 7 days) associated with omeprazole (10 mg/kg or vehicle) on nitrite and nitrate and nitrosylated species (RXNO) concentrations (measured using ozone-based chemiluminescence methods) assessed in the plasma, aorta, heart, liver, brain, and muscle. While our results showed that NO metabolite accumulation in different organs is not uniform, we found that the skeletal muscle, the heart, and the liver accumulate NO metabolites, particularly RXNO. This response was significantly attenuated by omeprazole in the heart and in the skeletal muscle. Together, these findings may indicate that the skeletal muscle, the heart, and the liver are major reservoir sites for NO metabolites after oral nitrite treatment, with major increases in nitrosylated species.

摘要

亚硝酸盐是一氧化氮(NO)的代谢产物,它可能在体内被生物激活以生成NO,并补充内源性NO的形成,尤其是在心血管疾病和代谢性疾病中。然而,口服亚硝酸盐治疗是否会导致不同器官中NO代谢产物的积累尚不清楚。此外,胃酸分泌抑制剂奥美拉唑的治疗会严重影响口服亚硝酸盐治疗诱导的胃中S-亚硝基硫醇的形成。然而,之前没有研究考察过奥美拉唑是否会影响亚硝酸盐诱导的不同器官中NO代谢产物的积累。本研究在大鼠中考察了口服亚硝酸钠治疗(15 mg/kg,灌胃1天或7天)联合奥美拉唑(10 mg/kg或赋形剂)对血浆、主动脉、心脏、肝脏、大脑和肌肉中亚硝酸盐、硝酸盐和亚硝基化物质(RXNO)浓度(使用基于臭氧的化学发光方法测量)的影响。虽然我们的结果表明不同器官中NO代谢产物的积累并不均匀,但我们发现骨骼肌、心脏和肝脏会积累NO代谢产物,尤其是RXNO。奥美拉唑在心脏和骨骼肌中显著减弱了这种反应。总之,这些发现可能表明,口服亚硝酸盐治疗后,骨骼肌、心脏和肝脏是NO代谢产物的主要储存部位,亚硝基化物质有显著增加。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3634/10967563/327b2c415e35/antioxidants-13-00255-g001.jpg

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