Ulinastatin attenuates diabetes-induced cardiac dysfunction by the inhibition of inflammation and apoptosis

Wang, Wenke; Lu, Qinghua; Wang, Xin; Wang, Ben; Wang, Juan; Gong, Hai‐Bin; Wang, Lin; Li, Hao; Du, Yong

doi:10.3892/etm.2017.4824

Cited by 16 publications

(19 citation statements)

References 43 publications

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“…It also inhibits the generation of myocardial inhibitory factor, reducing the production of oxygen free radicals and inhibiting the excessive release of various inflammatory mediators. It is widely used in the treatment of SIRS and other diseases (29,30). The protective mechanism of ulinastatin can be attributed to the inhibited production of pro-inflammatory cytokines (31), The effect of ulinastatin on respiratory function after CPB under DHCA could improve oxygenation (32).…”

Section: Discussionmentioning

confidence: 99%

Inflammation is related to preoperative hypoxemia in patients with acute Stanford type A aortic dissection

Duan¹,

Zhao²,

Lu³

et al. 2018

J. Thorac. Dis.

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Section: Discussionmentioning

confidence: 99%

Inflammation is related to preoperative hypoxemia in patients with acute Stanford type A aortic dissection

Duan¹,

Zhao²,

Lu³

et al. 2018

J. Thorac. Dis.

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“…20 As an acidic protein, ulinastatin can inhibit the activity of various enzymes and the production of many inflammatory factors and mediators. [21][22][23] In addition, it can directly bind with toxins and protect the body. Consequently, ulinastatin has been used to treat acute pancreatitis, acute circulatory failure, acute lung injury and many other severe infectionrelated diseases.…”

Section: Introductionmentioning

confidence: 99%

<p>Combination of Glutamine and Ulinastatin Treatments Greatly Improves Sepsis Outcomes</p>

Wang¹,

Zhou²,

Bai³

2020

JIR

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Background: Sepsis is one of the most dangerous syndromes, has extremely high mortality, and is caused by the body's extreme responses to an infection. The pathogenesis of sepsis is very complex and remains largely unknown and thus the treatments for sepsis are limited. Here, we evaluated the treatment results of two potential drugs, glutamine and ulinastatin, on sepsis. Methods: CLP rat model was used to study sepsis. Gastrostomy was performed to deliver the drugs. Flow cytometry was employed to measure CD4 and CD8 levels. May-Grünwald-Giemsa staining was used to count the numbers of monocytes and neutrophils in the blood. ELISA assay was performed to assess the levels of PCT, IL-6, TNFα, and IL-1β. Results: Sepsis was successfully induced with the standard CLP rat model. Both glutamine and ulinastatin treatments greatly improved the outcomes of sepsis, but the combination of both treatments had the maximum therapeutic effect. Mechanistically, PCT, IL-6, TNFα, and IL-1β levels were significantly diminished following glutamine and ulinastatin treatments, suggesting an inhibition of inflammatory responses. Further, CD4 and CD4/CD8 ratio, and the numbers of monocytes and neutrophils were greatly up-regulated by glutamine and ulinastatin, indicating an enhanced immunity. Conclusion: Glutamine and ulinastatin treatments largely mitigate sepsis shock by suppressing the inflammatory responses of the body and strengthening the immune system. Combination of these two drugs could serve as a potential treatment for sepsis.

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“…A number of studies have been performed to explore potential critical signaling pathways in DM (3)(4)(5). For example, in the pathogenesis of diabetic cardiomyopathy, the state of chronic hyperglycemia increases the formation of diacylglycerol (DAG), activates protein kinase C (PKC) and accelerates non-enzymatic formation of advanced glycated end products (6).…”

Section: Introductionmentioning

confidence: 99%

Metoprolol and bisoprolol ameliorate hypertrophy of neonatal rat cardiomyocytes induced by high glucose via the PKC/NF‑κB/c‑fos signaling pathway

Wei

Zhao

et al. 2019

Exp Ther Med

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Hyperglycemia caused by diabetes mellitus could increase the risk of diabetic cardiomyopathy. However, to the best of our knowledge, the underlying mechanism of this process is still not fully explored. Thus, developing ways to prevent hyperglycemia can be beneficial for diabetic patients. The present study was designed to investigate the influence of metoprolol and bisoprolol on the cardiomyocytic hypertrophy of neonatal rat cardiomyocytes. Cardiomyocytes were cultured in two types of media: One with low glucose levels and one with high glucose levels. Cardiomyocytes cultured in high glucose were further treated with the following: A protein kinase C (PKC) inhibitor, an NF-κB inhibitor, metoprolol or bisoprolol. The pulsatile frequency, cellular diameter and surface area of cardiomyocytes were measured. Protein content and [ 3 H]-leucine incorporation were determined, atrial natriuretic peptide (ANP), α-myosin heavy chain (α-MHC) and β-myosin heavy chain (β-MHC) mRNA levels were calculated by reverse transcription-quantitative PCR, while the expression and activation of PKC-α, PKC-β 2 , NF-κB, tumor necrosis factor-α (TNF-α), and c-fos were detected by western blotting. Metoprolol or bisoprolol were also used in combination with PKC inhibitor or NF-κB inhibitor to determine whether the hypertrophic response would be attenuated to a lower extent compared with metroprolol or bisoprolol alone. Cardiomyocytes cultured in high glucose presented increased pulsatile frequency, cellular diameter, surface area, and protein content and synthesis, higher expression of ANP and β-MHC, and lower α-MHC expression. High glucose levels also upregulated the expression and activation of PKC-α, PKC-β 2 , NF-κB, TNF-α and c-fos. Metoprolol and bisoprolol partly reversed the above changes, while combined use of metoprolol or bisoprolol with PKC inhibitor or NF-κB inhibitor further ameliorated the hypertrophic response mentioned above to lower levels compared with using metroprolol or bisoprolol alone. In conclusion, metoprolol and bisoprolol could prevent hypertrophy of cardiomyocytes cultured in high glucose by the inhibition of the total and phospho-PKC-α, which could further influence the PKC-α/NF-κB/c-fos signaling pathway.

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Ulinastatin attenuates diabetes-induced cardiac dysfunction by the inhibition of inflammation and apoptosis

Cited by 16 publications

References 43 publications

Inflammation is related to preoperative hypoxemia in patients with acute Stanford type A aortic dissection

Inflammation is related to preoperative hypoxemia in patients with acute Stanford type A aortic dissection

<p>Combination of Glutamine and Ulinastatin Treatments Greatly Improves Sepsis Outcomes</p>

Metoprolol and bisoprolol ameliorate hypertrophy of neonatal rat cardiomyocytes induced by high glucose via the PKC/NF‑κB/c‑fos signaling pathway

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