Ferroptosis inhibition attenuates inflammatory response in mice with acute hypertriglyceridemic pancreatitis

BACKGROUND Ferroptosis is involved in developing inflammatory diseases;yet,its role in acute hypertriglyceridemic pancreatitis(HTGP)remains unclear.AIM To explore whether ferroptosis is involved in the process of HTGP and elucidate its potential mechanisms.METHODS An HTGP mouse model was induced using intraperitoneal injection of P-407 and caerulein(CAE).Then,pancreatic tissues from the model animals were subjected to proteome sequencing analysis.The pathological changes and scores of the pancreas,lung,and kidney were determined using hematoxylin-eosin staining.The levels of serum amylase(AMY),triglyceride,and total cholesterol were measured with an automatic blood cell analyzer.Additionally,the serum levels of tumor necrosis factor(TNF)-α,interleukin(IL)-6,and IL-1βwere determined by enzyme linked immunosorbent assay.Malonaldehyde(MDA),glutathione(GSH),and Fe^(2+)were detected in the pancreas.Finally,immunohistochemistry was performed to assess the expression of ferroptosis-related proteins.RESULTS Proteome sequencing revealed that ferroptosis was involved in the process of HTGP and that NADPH oxidase(NOX)2 may participate in ferroptosis regulation.Moreover,the levels of serum AMY,TNF-α,IL-6,and IL-1βwere significantly increased,MDA and Fe^(2+)were upregulated,GSH and ferroptosis-related proteins were reduced,and the injury of the pancreas,lung,and kidney were aggravated in the P407+CAE group compared to CAE and wild type groups(all P<0.05).Notably,the inhibition of ferroptosis and NOX2 attenuated the pathological damage and the release of TNF-α,IL-6,and IL-1βin the serum of the mice.CONCLUSION Ferroptosis was found to have an important role in HTGP and may be considered a potential target for clinical treatment.

Chaiqin Chengqi Decoction as an adjuvant treatment for mild/moderately severe hypertriglyceridemic acute pancreatitis: A retrospective study

Hypertriglyceridemia is the third leading cause of acute pancreatitis(AP),and its incidence is increasing.Due to its relatively insidious etiology,it is easy to be ignored in the early stages.In China,Chaiqin Chengqi Decoction(CQCQD)has long been employed for treating AP.AIM To evaluate the effectiveness of CQCQD in patients diagnosed with mild/moderately severe hypertriglyceridemic AP(HTG-AP).METHODS In this study,the clinical data of 39 patients with HTG-AP admitted from January 2019 to November 2022 were collected.The changes of blood lipids,gastrointestinal symptoms,and abdominal pain before and after treatment were analyzed and compared between the two groups.RESULTS Twenty patients were treated with the conventional HTG-AP regimen,and 19 patients were additionally treated with CQCQD.After receiving treatment,the triglycerides(TG)level of the CQCQD group was lower than that of the CQCQD group(3.14±0.25 mmol/L vs 4.96±0.47 mmol/L,P<0.01).After 3 d of treatment,the patients in the CQCQD group had more bowel movements than the control group(2.51±0.25 times vs 1.00±0.17 times,P=0.01).The gastrointestinal function of most patients returned to normal,and the acute gastrointestinal injury score was significantly lower than that of the control group(0.11±0.07 vs 0.42±0.11,P<0.01).CONCLUSION In patients with HTG-AP,CQCQD can significantly reduce the TG level,shorten the recovery time of defecation,significantly improve the gastrointestinal function.

Incidence and clinical treatment of hypertriglyceridemic acute pancreatitis:A few issues

Hypertriglyceridemia is a well-recognized etiology of acute pancreatitis,and the incidence of hypertriglyceridemic acute pancreatitis(HTG-AP)has increased in frequency worldwide in response to lifestyle changes.It is crucial to identify hypertriglyceridemia as the cause of pancreatitis and initiate appropriate treatment.Insulin treatment produces effective lowering of triglycerides,but in our opinion,non-diabetic patients with HTG-AP require separate consideration to avoid hypoglycemia.

Incidence and clinical characteristics of hypertriglyceridemic acute pancreatitis:A retrospective single-center study

BACKGROUND The incidence of hypertriglyceridemic acute pancreatitis(HTG-AP)has increased yearly,but updated population-based estimates on the incidence of HTG-AP are lacking.Reducing serum triglyceride(TG)levels quickly is crucial in the early treatment of HTG-AP.Decreased serum TG levels are treated by non-invasive methods,which include anti-lipidemic agents,heparin,low-molecular weight heparin,and insulin,and invasive methods,such as blood purification including hemoperfusion(HP),plasmapheresis,and continuous renal replacement therapy.However,authoritative guidelines have not been established.Early selection of appropriate treatment is important and beneficial in controlling the development of HTG-AP.AIM To evaluate the effect between patients treated with intravenous insulin(INS)and HP to guide clinical treatment.METHODS We retrospectively reviewed 371 patients with HTG-AP enrolled in the Department of Fujian Provincial Hospital form April 2012 to March 2021.The inpatient medical and radiologic records were reviewed to determine clinical features,severity,complications,mortality,recurrence rate,and treatment.Multivariate logistic regression analyses were used to analyze risk factors for severe HTG-AP.Propensity score matching was used to compare the clinical outcomes of INS and HP.RESULTS A total of 371 patients met the HTG-AP criteria.The incidence of HTG-AP was increased by approximately 2.6 times during the 10 years(8.4%in April 2012-March 2013 and 22.3%in April 2020-March 2021).The highest incidence rate of acute pancreatitis was observed for men in the age group of 30-39 years.The amylase level was elevated in 80.1%of patients but was only three times the normal value in 46.9%of patients.The frequency of severe acute pancreatitis(26.9%),organ failure(31.5%),rate of recurrence(32.9%),and mortality(3.0%)of HTG-AP was high.Improved Marshall score,modified computed tomography severity index score,baseline TG,baseline amylase,C-reactive protein(CRP),albumin,aspartate aminotransferase,low-density lipoprotein cholesterol,urea nitrogen,creatinine,calcium,hemoglobin,free triiodothyronine,admission to intensive care unit,and mortality were significantly different between patients with different grades of severity(P<0.050).Multivariate logistic regression analysis confirmed that high CRP[P=0.005,odds ratio(OR)=1.011,95%CI:1.003-1.019],low calcium(P=0.003,OR=0.016,95%CI:0.001-0.239),and low albumin(P=0.023,OR=0.821,95%CI:0.693-0.973)were risk factors of severe HTG-AP.After propensity score matching adjusted by sex,age,severity of HTG-AP,and baseline TG,the serum TG significantly decreased in patients treated with INS(P<0.000)and HP(P<0.000)within 48 h.However,the clearance rate of TG(57.24±33.70%vs 56.38±33.61%,P=0.927)and length of stay(13.04±7.92 d vs 12.35±6.40 d,P=0.730)did not differ between the two groups.CONCLUSION The incidence of HTG-AP exhibited a significant increase,remarkable severity,and recurrent trend.Patients with mild and moderately severe acute pancreatitis can be treated effectively with INS safely and effectively without HP.