Picroside II Improves Severe Acute Pancreatitis-Induced Hepatocellular Injury in Rats by Affecting JAK2/STAT3 Phosphorylation Signaling

Piao, Xuehua; Sui, Xiaodan; Liu, Baohai; Cui, Tingfang; Qi, Zinan

doi:10.1155/2021/9945149

Cited by 3 publications

(2 citation statements)

References 37 publications

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“…The metabolic and exocrine dysfunction caused by liver injury further aggravates the failure of other vital organs, forming a second hit for the patient. The invasion of peripancreatic necrosis products combined with hematogenous spread of intestinal bacteria results in destruction of the liver parenchyma[ 5 , 6 ]. Disorders of liver cell metabolism and exocrine function further aggravate the failure of the lung, kidney and other important organs, forming the second hit after the onset of SAP[ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Milk fat globule epidermal growth factor 8 alleviates liver injury in severe acute pancreatitis by restoring autophagy flux and inhibiting ferroptosis in hepatocytes

Cui,

Liu,

Liu

et al. 2024

World J Gastroenterol

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BACKGROUND Liver injury is common in severe acute pancreatitis (SAP). Excessive autophagy often leads to an imbalance of homeostasis in hepatocytes, which induces lipid peroxidation and mitochondrial iron deposition and ultimately leads to ferroptosis. Our previous study found that milk fat globule epidermal growth factor 8 (MFG-E8) alleviates acinar cell damage during SAP via binding to αvβ3/5 integrins. MFG-E8 also seems to mitigate pancreatic fibrosis via inhibiting chaperone-mediated autophagy. AIM To speculate whether MFG-E8 could also alleviate SAP induced liver injury by restoring the abnormal autophagy flux. METHODS SAP was induced in mice by 2 hly intraperitoneal injections of 4.0 g/kg L-arginine or 7 hly injections of 50 μg/kg cerulein plus lipopolysaccharide. mfge8 -knockout mice were used to study the effect of MFG-E8 deficiency on SAP-induced liver injury. Cilengitide, a specific αvβ3/5 integrin inhibitor, was used to investigate the possible mechanism of MFG-E8. RESULTS The results showed that MFG-E8 deficiency aggravated SAP-induced liver injury in mice, enhanced autophagy flux in hepatocyte, and worsened the degree of ferroptosis. Exogenous MFG-E8 reduced SAP-induced liver injury in a dose-dependent manner. Mechanistically, MFG-E8 mitigated excessive autophagy and inhibited ferroptosis in liver cells. Cilengitide abolished MFG-E8’s beneficial effects in SAP-induced liver injury. CONCLUSION MFG-E8 acts as an endogenous protective mediator in SAP-induced liver injury. MFG-E8 alleviates the excessive autophagy and inhibits ferroptosis in hepatocytes by binding to integrin αVβ3/5.

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Section: Introductionmentioning

confidence: 99%

Milk fat globule epidermal growth factor 8 alleviates liver injury in severe acute pancreatitis by restoring autophagy flux and inhibiting ferroptosis in hepatocytes

Cui,

Liu,

Liu

et al. 2024

World J Gastroenterol

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“…Today, acute pancreatitis (AP) is a common form of acute abdomen in the clinic, the incidence of which has been increasing in recent years [2,7,9,10]. AP is a serious systemic inflammatory disease and often leads to distant organ dysfunction with high morbidity and mortality [1,8,11]. Acute lung injury is one of the most serious and earliest injuries of AP.…”

Section: Introductionmentioning

confidence: 99%

Ultrastructural changes of hemocapillaries of the lungs in the late development of experimental acute pancreatitis

Zaiats,

Pasichnyk,

Zukow

2024

J Educ Health Sport

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Background. Today, acute pancreatitis is a common form of acute abdomen in the clinic, the incidence of which has been increasing in recent years. The aim of the work was to study the dynamics of ultrastructural changes of the hemocapillaries of the alveolar wall of the lungs in the late stages of experimental acute pancreatitis. Material and methods. The experiments were carried out on 54 white Wistar male rats weighing 180–220 g. The animals were divided into three groups: first — intact, second — control, third — experimental with a model of acute pancreatitis, which was reproduced by intraperitoneal administration of a 20% solution of L-arginine at a total dose of 5 g/kg at one-hour interval. The control group of animals was intraperitoneally injected with an equivalent dose of isotonic sodium chloride solution. All research were performed under sodium thiopental anesthesia at the rate of 60 mg/kg body weight. Lung tissue for electron microscopic examination was collected from the lower lobe of the left lung at 3–5 and 7 days. Pieces of lung tissue measuring 1×1×1 mm were fixed in a 2.5% glutaraldehyde solution, followed by additional fixation in a 1% osmium tetroxide solution. After dehydration, the material was poured into Epon-Araldite. Sections with a thickness of 20–50 nm obtained on “Tesla BS-490” ultramicrotome were studied in a PEM-125K electron microscope. Results. The ultrastructural analysis showed that already 3 days after the study, dystrophic-destructive changes, as well as adhesion and aggregation of leukocytes, were detected in the endothelial cells. As the study period increased (5–7 days), the intensity of changes in the hemocapillaries of the alveolar wall increased significantly. In the lumen erythrocyte sludge, thromboleukocyte adhesion and aggregation are determined in hemocapillaries. Conclusion. Acute experimental pancreatitis is accompanied by marked changes in the ultrastructural structure of hemocapillaries of the alveolar wall. The nature and severity of structural changes in the hemocapillaries of the alveolar wall depends on the duration of the course of arginine-induced acute pancreatitis.

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Zerumbone ameliorates the inflammatory response and organ damage in severe acute pancreatitis via the ROS/NF-κB pathway

Zhang,

2023

BMC Gastroenterol

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Objective The aim of the current study was to determine the mechanism by which Zerumbone (ZER) ameliorates inflammation and organ damage in a rat model of severe acute pancreatitis (SAP). Methods Different concentrations of ZER (10, 20 and 40 mg/kg) were administered by femoral vein puncture 30 min prior to establishment of the SAP model. Hematoxylin and eosin (H&E) staining was used to assess pathological changes in the pancreatic tissue of SAP-induced rats. The lung wet/dry (W/D) ratio was assessed and serum levels of amylase (AMY), alanine aminotransferase (ALT), creatinine (Cr), aspartate aminotransferase (AST) and phospholipase A2 (PLA2) were measured. Western blot analysis was used to examine changes in the expression of ROS/NF-κB pathway-associated proteins. Results SAP was confirmed by significant histopathological damage to the pancreas. ZER (10, 20 and 40 mg/kg) was found to alleviate pancreatitis and decrease ascites volume, lung W/D ratio, pancreatic pathology score, oxidative stress and inflammatory damage. High concentrations (20 and 40 mg/kg) of ZER were shown to increase levels of hepatorenal toxicity. In contrast, 10 mg/kg ZER was found to attenuate liver enzyme levels, reduce pathological damage to the liver, and protect against extrapancreatic organ damage to the liver in SAP-induced rats. Moreover, ZER showed no significant side effects in normal rats. Finally, we demonstrated that ZER mediated its anti-inflammatory effects on SAP through the ROS/NF-κB signaling pathway. Conclusion ZER alleviated SAP-induced oxidative stress and inflammatory injury via the ROS/NF-κB pathway, and had a protective effect on lung injury and liver damage.

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Picroside II Improves Severe Acute Pancreatitis-Induced Hepatocellular Injury in Rats by Affecting JAK2/STAT3 Phosphorylation Signaling

Cited by 3 publications

References 37 publications

Milk fat globule epidermal growth factor 8 alleviates liver injury in severe acute pancreatitis by restoring autophagy flux and inhibiting ferroptosis in hepatocytes

Milk fat globule epidermal growth factor 8 alleviates liver injury in severe acute pancreatitis by restoring autophagy flux and inhibiting ferroptosis in hepatocytes

Ultrastructural changes of hemocapillaries of the lungs in the late development of experimental acute pancreatitis

Zerumbone ameliorates the inflammatory response and organ damage in severe acute pancreatitis via the ROS/NF-κB pathway

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