Crucial role of group IIA phospholipase A2 in pancreatitis-associated adrenal injury in acute necrotizing pancreatitis

Xu, Shang‐Zhong; Chen, Chen; Wang, Weixing; Huang, Shun-Rong; Yu, Jie-Ping; Chen, Xiaoyan

doi:10.1016/j.prp.2009.03.002

Cited by 11 publications

(10 citation statements)

References 35 publications

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“…Our findings demonstrated that apoptotic nucleus with chromatin condensation, chromatin margination, and loss of the nuclear membrane integrity was proved under electron microscope. Both the elevated activity of sPLA 2 and the protein expression of sPLA 2 -IIA were followed by endocrine function and tissue structure damage in the adrenal cortex after pancreatitis, and our previous study confirmed that the sPLA 2 inhibitor ameliorated the histopathologic score and apoptosis index of adrenal cortex (part of data not shown) [31]. A review focusing on inflammatory mediators such as TNF-α, IL-1β, IL-6, endotoxin, PGF 2 , and TXA 2 revealed that these mediators can influence the synthesis of glucocorticoid by interfering the corticotropin-releasing hormone and adrenocorticotropic hormone activity [40].…”

Section: Discussionsupporting

confidence: 54%

“…Besides vacuolar and granular degenerations, we have also observed that steatosis as well as vacuolar and granular degenerations of different extents exist in adrenocortical cells during pancreatitis, and degeneration, necrosis, and hemorrhage are common findings of acute adrenocortical injury [31,47]. Hemorrhagic necrosis, degeneration, and neutrophil infiltration in adrenal cortex on H&E staining were also observed in ANP animals.…”

Section: Discussionmentioning

confidence: 83%

“…However, RAI was coined to describe a syndrome where the adrenal gland partially respond to stress, but the magnitude of response is not commensurate with the degree of stress [39]. AI may be part of APassociated multi-organ dysfunctions [31] and may have some association with the rapid progression and destruction of necrotizing pancreas [15], high incidence of complications, and high mortality in pancreatitis [4]. Exhaustion of adrenal cortex has been considered as responsible for AI in the early last century and proposed possible mechanisms for adrenal suppression during inflammation include direct inhibition of ACTH stimulation on adrenal cells, decreased pituitary response to CRH, interference with cortisol binding, release of adrenal contents of cAMP, and diminished adrenal blood flow [40][41][42][43][44].…”

Section: Discussionmentioning

confidence: 99%

“…All the rats were randomly assigned into sham operation (control, n=40) or acute necrotizing pancreatitis groups (ANP, n= 40). Two groups were divided into five subgroups for the time points 0, 3, 6, 12, and 24 h (n=8) after the injection of sodium taurocholate, respectively, based on previous reports [30][31][32].…”

Section: Animals and Groupingmentioning

confidence: 99%

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Changes of Inflammation and Apoptosis in Adrenal Gland After Experimental Injury in Rats with Acute Necrotizing Pancreatitis

Wang

et al. 2010

Inflammation

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We hypothesize that adrenal insufficiency in acute necrotizing pancreatitis (ANP) is attributable to hemorrhagic inflammation, necrosis, and apoptosis of the adrenal cortex. Arguments to support this view are presented in the study that investigated morphological and functional changes of adrenal and the distinct roles of inflammatory mediator secretory phospholipase A(2) (sPLA(2)) and apoptosis-related genes Bax and Bcl-2 played in acute adrenal injury in ANP. After ANP model was induced, pancreatic histology, serum amylase, sPLA(2), and corticosterone were analyzed. The adrenal morphology, apoptotic cells by TUNEL assay, and ultrastructures were observed. sPLA(2)-IIA and Bcl-2 and Bax expressions were detected by immunohistochemistry. Histopathologic grading of adrenal was higher in ANP group than in controls. Serum corticosterone was stimulated to maximal level at 3 h, then dropped to the bottom at 24 h (P<0.05). Apoptotic index, sPLA2-IIA, and Bax expression were increased steeply after pancreatitis, and the Bax/Bcl-2 ratio was elevated gradually (P<0.05). Sustained decrease in serum corticosterone level following adrenal injury during ANP appears to be, in part, due to the crucial roles of inflammation and apoptosis in adrenal cortex. These findings could suggest that sPLA2, Bax, and Bcl-2 may be involved in the course of adrenal injury after ANP.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Animals and Groupingmentioning

confidence: 99%

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Changes of Inflammation and Apoptosis in Adrenal Gland After Experimental Injury in Rats with Acute Necrotizing Pancreatitis

Wang

et al. 2010

Inflammation

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“…Another key factor is organic damage to the adrenal gland. In animal models of acute necrotizing pancreatitis (ANP), adrenal insufficiency could be largely attributed to pathologically verifiable damage to the adrenal gland [ 6 , 7 ], caused by a variety of pathological processes, including ischemia, hemorrhage, inflammation, and apoptosis [ 1 , 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Poly(ADP-ribose) polymerase inhibition suppresses inflammation and promotes recovery from adrenal injury in a rat model of acute necrotizing pancreatitis

Zuo

Deng

et al. 2016

BMC Gastroenterol

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BackgroundPoly(ADP-ribose) polymerase (PARP) participates in multi-organ failure in various inflammatory diseases including acute necrotizing pancreatitis (ANP). Since pancreatitis-associated adrenal insufficiency is partly caused by inflammatory damage to the adrenal cortex, we examined whether PARP antagonism could alleviate adrenal insufficiency in a rat model of ANP.MethodsANP was induced by retrograde infusion of sodium taurocholate into the bile-pancreatic duct. At 30 min prior to taurocholate infusion, rats were pretreated with the PARP inhibitor 3-Aminobenzamide (3-AB, 20 mg/kg) or vehicle. Pancreatic pathological injury, adrenal histology, neutrophil infiltration, cell apoptosis, and serum corticosterone level were assessed at various times points. Activities of poly(ADP-ribosyl)ated protein (PAR), nuclear factor-kappaB (NF-kB), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and inducible nitric oxide synthase (iNOS) in the adrenal were also examined.ResultsPARP overactivation in ANP rats is associated with reduced serum corticosterone level and marked cellular alterations in adrenocortical tissue. Inflammatory stress caused by ANP reduced adrenal corticosterone release. 3-AB reduced the activation of PARP and inflammatory markers, decreased myeloperoxidase activity, attenuated adrenal morphologic lesions and cells apoptosis, simultaneously improved the impaired adrenal function.ConclusionsOur data demonstrate the involvement of PARP overactivation in the pathogenesis of adrenal dysfunction after ANP. PARP inhibition may suppress inflammation and promote functional recovery from adrenal injury.

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Impaired HPA axis function in diabetes involves adrenal apoptosis and phagocytosis

Repetto¹,

Wiszniewski²,

Bonelli³

et al. 2018

Endocrine

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Crucial role of group IIA phospholipase A2 in pancreatitis-associated adrenal injury in acute necrotizing pancreatitis

Cited by 11 publications

References 35 publications

Changes of Inflammation and Apoptosis in Adrenal Gland After Experimental Injury in Rats with Acute Necrotizing Pancreatitis

Changes of Inflammation and Apoptosis in Adrenal Gland After Experimental Injury in Rats with Acute Necrotizing Pancreatitis

Poly(ADP-ribose) polymerase inhibition suppresses inflammation and promotes recovery from adrenal injury in a rat model of acute necrotizing pancreatitis

Impaired HPA axis function in diabetes involves adrenal apoptosis and phagocytosis

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