N-acetylcysteine ameliorates liver injury in a rat model of intestinal ischemia reperfusion

Kalimeris, Konstantinos; Briassoulis, Panagiotis; Ntzouvani, Agathi; Nomikos, Tzortzis; Papaparaskeva, Kleio; Politi, Aikaterini; Batistaki, Chrysanthi; Kostopanagiotou, Georgia

doi:10.1016/j.jss.2016.08.049

Cited by 30 publications

(20 citation statements)

References 62 publications

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“…5,6 Moreover, the pathophysiology of remote liver injury after intestinal I/R remains only partially understood; putative mechanisms include sustained pro-inflammatory cytokine challenge and cytokines that are released or activated after enterocyte damage or death. 7,8 If liver repair and regenerative mechanisms are not activated promptly, especially in patients with chronic liver disease or after liver transplantation, acute liver functional impairment, or poor early graft function will occur. 9 Despite extensive studies, effective multiple organ protective interventions with clinically proven efficacy remain to be developed.…”

Section: Introductionmentioning

confidence: 99%

HMGB1‐associated necroptosis and Kupffer cells M1 polarization underlies remote liver injury induced by intestinal ischemia/reperfusion in rats

Wen

Ling

et al. 2020

FASEB j.

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Reperfusion of the ischemic intestine often leads to drive distant organ injury, especially injuries associated with hepatocellular dysfunction. The precise molecular mechanisms and effective multiple organ protection strategies remain to be developed. In the current study, significant remote liver dysfunction was found after 6 hours of reperfusion according to increased histopathological scores, serum lactate dehydrogenase (LDH), alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels, as well as enhanced bacterial translocation in a rat intestinal ischemia/reperfusion (I/R) injury model. Moreover, receptor‐interacting protein kinase 1/3 (RIP1/3) and phosphorylated‐MLKL expressions in tissue were greatly elevated, indicating that necroptosis occurred and resulted in acute remote liver function impairment. Inhibiting the necroptotic pathway attenuated HMGB1 cytoplasm translocation and tissue damage. Meanwhile, macrophage‐depletion study demonstrated that Kupffer cells (KCs) are responsible for liver damage. Blocking HMGB1 partially restored the liver function via suppressed hepatocyte necroptosis, tissue inflammation, hepatic KCs, and circulating macrophages M1 polarization. What’s more, HMGB1 neutralization further protects against intestinal I/R‐associated liver damage in microbiota‐depleted rats. Therefore, intestinal I/R is likely associated with acute liver damage due to hepatocyte necroptosis, and which could be ameliorated by Nec‐1 administration and HMGB1 inhibition with the neutralizing antibody and inhibitor. Necroptosis inhibition and HMGB1 neutralization/inhibition, may emerge as effective pharmacological therapies to minimize intestinal I/R‐induced acute remote organ dysfunction.

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Section: Introductionmentioning

confidence: 99%

HMGB1‐associated necroptosis and Kupffer cells M1 polarization underlies remote liver injury induced by intestinal ischemia/reperfusion in rats

Wen

Ling

et al. 2020

FASEB j.

View full text Add to dashboard Cite

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“…Hepatic ischemia/reperfusion (HIR) is commonly performed in clinical liver surgeries including liver transplantation [ 1 ]. The pathogenesis of HIR injury is a complex process involving not only necrosis and apoptosis but also oxidative stress, inflammation, and dysfunction of the liver cells [ 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

Vildagliptin Attenuates Hepatic Ischemia/Reperfusion Injury via the TLR4/NF-κB Signaling Pathway

Sherif

Al-Shaalan

2018

Oxidative Medicine and Cellular Longevity

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The Toll-like receptor-4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway is vital in the pathogenesis of hepatic ischemia/reperfusion (HIR) injury. Dipeptidyl peptidase-4 (DPP4) inhibitors exert protective effects on IR injury of the kidney, heart, and lung; however, their effect on the liver is still unknown. Thus, the purpose of this study was to examine whether pretreatment with vildagliptin (Vilda), a DPP4 inhibitor, produces hepatic protection against IR injury and to investigate its influence on TLR4/NF-κB signaling in a rat model. Thirty male Wistar rats were divided into 3 groups: the sham group: subjected to a sham operation and received normal saline; the HIR group: subjected to HIR and received normal saline; and the Vilda + HIR group: subjected to HIR with pretreatment of 10 mg/kg/day Vilda for 10 days intraperitoneally. Hepatic ischemia lasted for 45 minutes followed by 3-hour reperfusion; then blood and liver samples were collected for biochemical and histopathological examination. The HIR group produced a significant increase in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatic malondialdehyde (MDA), nitric oxide (NO), and tumor necrosis factor alpha (TNF-α) levels and a significant reduction in the hepatic catalase level in comparison to the sham group. Moreover, a significant upregulation of gene and protein expressions of TLR4, NF-κB, and high-mobility group box-1 (HMGB1) along with caspase-3 protein expression was observed in the HIR group when compared with the sham group. Histopathological examination of the liver from the HIR group showed necrosis, sinusoidal congestion, hemorrhage, and hepatocyte degeneration. Administration of Vilda ameliorated the biochemical and histopathological changes caused by HIR. Vildagliptin showed for the first time a hepatoprotective effect in HIR injury through downregulation of TLR4/NF-κB/HMGB1 and caspase-3 hepatic expressions.

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“…In humans or experimental animals, the antioxidant NAC inhibits tissue damage caused by oxidative stress due to its anti-inflammatory and antioxidant properties [93,94]. NAC is an antioxidant with direct and indirect antioxidant action used in clinical practice [95]. NAC significantly alleviates remote liver injury in terms of morphology and transaminases, in a dose-depended manner, and reduces lipid peroxidation in serum.…”

Section: N-acetylcysteine (Nac)mentioning

confidence: 99%

Nonalcoholic Fatty Liver Disease: Pathogenesis and Treatment in Traditional Chinese Medicine and Western Medicine

Shi

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Nonalcoholic Fatty Liver Disease (NAFLD) is one of the most important causes of liver disease worldwide and probably destined to become the leading cause of end-stage liver disease in the coming decades, affecting both adults and children. Faced with the severe challenges for the prevention and control of NAFLD, this article discusses the understanding and mechanism of NAFLD from Chinese and Western medicine. Moreover, the progress regarding its treatment in both Chinese and Western medicine is also summarized. Both Chinese medicine and Western medicine have their own characteristics and clinical efficacy advantages in treating diseases. e purpose of this article is to hope that Chinese and Western medicine have complementary advantages, complementing each other to improve clinical NAFLD therapy prevention and treatment methods to receive more and more attention throughout the global medical community.

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N-acetylcysteine ameliorates liver injury in a rat model of intestinal ischemia reperfusion

Cited by 30 publications

References 62 publications

HMGB1‐associated necroptosis and Kupffer cells M1 polarization underlies remote liver injury induced by intestinal ischemia/reperfusion in rats

HMGB1‐associated necroptosis and Kupffer cells M1 polarization underlies remote liver injury induced by intestinal ischemia/reperfusion in rats

Vildagliptin Attenuates Hepatic Ischemia/Reperfusion Injury via the TLR4/NF-κB Signaling Pathway

Nonalcoholic Fatty Liver Disease: Pathogenesis and Treatment in Traditional Chinese Medicine and Western Medicine

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