Activation of central muscarinic receptor type 1 prevents development of endotoxin tolerance in rat liver

Eftekhari, Golnar; Hajiasgharzadeh, Khalil; Ahmadi-Soleimani, S. Mohammad; Dehpour, Ahmad Reza; Semnanian, Saeed; Mani, AR

doi:10.1016/j.ejphar.2014.06.050

Cited by 17 publications

(15 citation statements)

References 31 publications

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“…Reduced HRV might mean lower activity in the neural anti-inflammatory pathway and hence higher chance of organ damage/failure after minor infection (38,39) . Although evidence for the contribution of this neural anti-inflammatory pathway in cirrhosis is emerging (40)(41)(42), the exact mechanistic link awaits further investigation. One limitation of our study is that the cause of death was not registered in our study.…”

Section: Discussionmentioning

confidence: 99%

Which heart rate variability index is an independent predictor of mortality in cirrhosis?

Bhogal

Rui

Pavanello

et al. 2019

Digestive and Liver Disease

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Background: Liver cirrhosis is associated with reduced heart rate variability (HRV), which indicates impaired integrity of cardiovascular control in this patient population. There are several different indices for HRV quantification. The present study was designed to: 1) determine which of the HRV indices is best at predicting mortality in patients with cirrhosis; 2) verify if such ability to predict mortality is independent of the severity of hepatic failure. Methods: Ten minutes electrocardiogram was recorded in 74 patients with cirrhosis. Heart rate fluctuations were quantified using statistical, geometrical and non-linear analysis. The patients were followed-up for 18 months and information was collected on the occurrence of death/liver transplantation. Results: During the follow-up period, 24 patients (32%) died or were transplanted for hepatic decompensation. Cox's regression analysis showed that SDNN (total HRV), cSDNN (corrected SDNN), SD1 (short-term HRV), SD2 (long-terms HRV) and spectral indices could predict survival in these patients. However, only SD2 and cSDNN were shown to be independent of MELD in predicting survival. The prognostic value of HRV indices was independent of age, gender, use of beta blockers, and the aetiology of liver disease. Conclusion: Two HRV indices were identified that could predict mortality in patients with cirrhosis, independently of MELD. These indices are potentially useful tools for survival prediction.

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Section: Discussionmentioning

confidence: 99%

Which heart rate variability index is an independent predictor of mortality in cirrhosis?

Bhogal

Rui

Pavanello

et al. 2019

Digestive and Liver Disease

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“… 48 Recently, we showed that centrally cholinergic system activation prevents development of endotoxin tolerance in rat liver. 49 These studies suggest that neural impairment may occur during liver disease due to peripheral and central causes; however greater understanding of the underlying mechanisms of AD of cirrhosis is required. Regardless of the etiology of disease, AD has been suggested to predict poor prognosis in patients with cirrhosis.…”

Section: Introductionmentioning

confidence: 99%

Cholinergic Anti-Inflammatory Pathway and the Liver

Hajiasgharzadeh¹,

Baradaran²

2017

Adv Pharm Bull

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The hepatic vagus branches innervate the liver and serve an important role in liver-brain connection. It appears that brain modulates inflammatory responses by activation of vagal efferent fibers. This activation and subsequent acetylcholine releases from vagus nerve terminals leads to inhibition of inflammatory cytokines through α7 nicotinic acetylcholine receptors (α7nAChRs) which located on the surface of different cell types such as liver Kupffer cells. This protective role of vagus-α7nAChR axis in liver diseases has been shown in several experimental studies. On the other hand, accumulated evidence clearly demonstrate that, autonomic dysfunction which is reduced functioning of both vagal and sympathetic nervous system, occurs during chronic liver disease and is well-known complication of patients suffering from cirrhosis. This review describes the impact and significance of cholinergic anti-inflammatory pathway in the liver and discusses about its disease-related dysfunction on the progression of cirrhosis. Considering the fact that sepsis is major cause of death in cirrhotic patients, convergence of these findings, may lead to designing novel therapeutic strategies in the field of chronic liver diseases management involving selective drug targeting and electrical nerve stimulation.

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“…Chronic endotoxemia was induced by intraperitoneal injection of 1 mg/kg lipopolysaccharide (LPS, from Salmonella typhimurium) for 5 days. Control groups were considered by intraperitoneal injection of saline (1 ml/kg) for 5 days [6]. Animals were weighed before entering into study and also at the time of sacrifice.…”

Section: Animalsmentioning

confidence: 99%

“…Real time-PCR 5 and histopathological study examined receptors gene expression and protein localization. Cumulative 8-OH-DPAT caused relaxation in control aorta (EC50 6 7.79 ± 21.35 and 8.53 ± 10.74 with and without antagonist), which was enhanced in endotoxemia (EC50 6.35 ± 8.48 and very wide ± 17.38 with and without antagonist). Cumulative zolmitriptan caused relaxation in control aorta (EC50 very wide ± 8.65 and 8.38 ± 8.44 with and without antagonist), which was enhanced in endotoxemia (EC50 very wide ± 9.53 and 8.37 ± 13.49 with and without antagonist).…”

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confidence: 97%

Evaluation of Isolated Vascular Response to 5HT1A, 5HT1B1D & 5HT2A Receptors Agonist & Antagonist in Chronic Endotoxemic Rats

et al. 2018

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The main vascular feature in endotoxemia is impaired contractile responses to vasoactive agents. We study the aortic response to 5HT11 A, 5HT1B1D and 5HT2A receptors agonist and antagonist in chronic endotoxemic rats. Intraperitoneal injection of 1 mg/kg lipopolysaccharide for 5 days induced chronic endotoxemia. Control rats received intraperitoneal injection of 1 ml/kg saline for 5 days. Rats divided into 3 groups. In first, DOI2 hydrochloride used as an agonist and sarpogrelate hydrochloride as an antagonist of 5HT2A receptor. In second, (R)-(+)-8-OH-DPAT3 and WAY1001354 used as an agonist and antagonist of 5HT1A receptor respectively. In third, Zolmitriptan used as an agonist and GR127935 hydrochloride as an antagonist of 5HT1B1D receptor. Aorta Isolated for organ bath study. Real time-PCR5 and histopathological study examined receptors gene expression and protein localization. Cumulative 8-OH-DPAT caused relaxation in control aorta (EC506 7.79±21.35 and 8.53±10.74 with and without antagonist), which was enhanced in endotoxemia (EC50 6.35±8.48 and very wide±17.38 with and without antagonist). Cumulative zolmitriptan caused relaxation in control aorta (EC50 very wide±8.65 and 8.38±8.44 with and without antagonist), which was enhanced in endotoxemia (EC50 very wide±9.53 and 8.37±13.49 with and without antagonist). DOI hydrochloride contracted the control aorta (EC50 6.51±7.14 and 5.98±1.65 with and without antagonist), which was converted to relaxation in endotoxemic group (EC50 infinity±80.43 and 7.37±20.28 with and without antagonist). PCR studies revealed enhanced 5HT1A receptor and diminished 5HT1B1D and 5HT2A receptor genes expression, while histopathological studies showed inflamed, damaged endothelium in endotoxemic aorta. Our data supports enhanced vasodilation and impaired vasoconstriction during endotoxemia.

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Activation of central muscarinic receptor type 1 prevents development of endotoxin tolerance in rat liver

Cited by 17 publications

References 31 publications

Which heart rate variability index is an independent predictor of mortality in cirrhosis?

Which heart rate variability index is an independent predictor of mortality in cirrhosis?

Cholinergic Anti-Inflammatory Pathway and the Liver

Evaluation of Isolated Vascular Response to 5HT1A, 5HT1B1D & 5HT2A Receptors Agonist & Antagonist in Chronic Endotoxemic Rats

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