Antioxidant Therapy in Pancreatitis

Swentek, Lourdes; Chung, Dean; Ichii, Hirohito

doi:10.3390/antiox10050657

Cited by 18 publications

(13 citation statements)

References 138 publications

(165 reference statements)

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“…CP is a long-term, irreversible, inflammatory disease of the pancreas that is accompanied by increased OS in pancreatic tissue. 35 Specifically, when pancreatic tissue is affected by pathogenic factors, acinar cells are damaged by OS, resulting in increased neutrophil infiltration, and hence pancreatic inflammation 36 as well as increased selective macrophage activation against the early pro-inflammatory effects of neutrophils. Further, under such conditions, macrophage activation initiates tissue repair, leading to the activation of PSCs.…”

Section: Discussionmentioning

confidence: 99%

Antioxidant Mitoquinone Alleviates Chronic Pancreatitis via Anti-Fibrotic and Antioxidant Effects

Li¹,

Yuan²,

Han³

et al. 2022

JIR

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Background Chronic pancreatitis (CP) is a long-term inflammatory disease of the pancreas that can be caused by various pathogenic factors. Oxidative stress (OS), which is associated with several pancreatic diseases, can induce pancreatic stellate cell (PSC) activation, leading to pancreatic fibrosis. Given the inefficacy of existing treatments for CP, in this study, our objective was to evaluate the therapeutic effect of the antioxidant, mitoquinone (MitoQ). Methods First, in vivo, we established a CP mouse model via the repeated injection of cerulein. Mice in the MitoQ group simultaneously received MitoQ daily. After 4 weeks of cerulein injection, pancreatic tissues from mice were evaluated by morphological changes and the expression of fibrosis markers. Further, OS in the collected pancreatic tissue samples was evaluated by determining the level of malondialdehyde (MDA) as well as the expression levels and activities of antioxidants. Furthermore, in vitro, the effect of MitoQ on human PSCs (hPSCs) was evaluated based on PSC activation markers and fibrotic phenotypes, and OS in these treated hPSCs was evaluated by measuring reactive oxygen species (ROS), MDA, and antioxidant levels. Results In vivo, MitoQ alleviated pancreatic fibrosis and inhibited OS in the cerulein-induced murine CP model. In vitro, it inhibited PSC activation as well as the subsequent development of the profibrogenic phenotypes by balancing out the levels of free radicals and the intracellular antioxidant system. Conclusion MitoQ is a potential candidate for CP treatment.

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Section: Discussionmentioning

confidence: 99%

Antioxidant Mitoquinone Alleviates Chronic Pancreatitis via Anti-Fibrotic and Antioxidant Effects

Li¹,

Yuan²,

Han³

et al. 2022

JIR

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“…ОС є каталізатором активації зірчастих клітин ПЗ, що призводить до відкладення колагенового позаклітинного матриксу, який викликає фіброз ПЗ [2]. Сучасні дослідження спрямовані на детальні вивчення патофізіології ПЗ з акцентом на ОС і те, як він сприяє ускладненням хвороби [3]. Пацієнти з ХП мають нижчий рівень антиоксидантів і підвищену активність вільних радикалів, порівняно зі здоровими дорослими, і посилення регуляції генів реакції на стрес при ХП [4,5,6,7].…”

Section: Discussionunclassified

Assessment of the state of the oxidant-antioxidant system and lipid peroxidation in patients with chronic pancreatitis combined with hypothyroidism

Ratsa¹,

Федів²

2021

Buk. Med. Herald

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Changes in oxidative-antioxidant homeostasis is one of the pathogenetic links in the onset and progression of many nosologies, including chronic pancreatitis (CP) and hypothyroidism (HТ), however, data on the development of oxidative stress (OS) with a combination of CP and HP are insufficient, therefore, determining the role of these systems with a comorbid course of these pathologies is an urgent issue of our time.The aim of the work is to study the state of the oxidative and antioxidant system in patients with CP and CP combined with HT.Material and methods. 96 people were examined, including 26 patients with chronic pancreatitis (group 1), 24 patients with hypothyroidism (group 2), 26 patients with chronic pancreatitis on the background of hypothyroidism (group 3), 20 almost healthy individuals (group 4). Evaluation of the oxidative-antioxidant system and lipid peroxidation was assessed by determining the content of malonic aldehyde in blood plasma (MA pl.) And erythrocytes (MA er.), The level of reduced glutathione, glutathione peroxidase (GP) and glutathione-S-trans-ion (GT). Enzyme activity was calculated per 1 g of hemoglobin (HB).Research results. The analysis of the obtained results revealed clear patterns of changes in the state of the oxidative-antioxidant system and lipid peroxidation in patients with chronic pancreatitis on the background of hypothyroidism. Namely, violation of lipid peroxidation in patients with comorbid pathology, accompanied by an increase in the content of MA er. by 44.87% and the content of MA in blood plasma by 46.42%; oxidative-antioxidant system: decrease in HF in the blood by 51,61%, combined of a compensatory increase in BP - by 48.03% and HT - by 34.76%.Conclusion. Under the conditions of comorbidity of CP and HT, there is a violation of the oxidative-antioxidant system and the state of lipid peroxidation, which is characterized by a significant increase in MA in erythrocytes and MA in plasma against a decrease in glutathione and which complicates the course of the underlying disease, its diagnosis and treatment.

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“…Thioredoxin-interacting protein (TXNIP) [6][7][8][9][10] is an endogenous thioredoxin negative modulator that plays an important role in retaining the redox balance in cells, which is involved in cell proliferation, differentiation and apoptosis [7]. Thioredoxin is usually a small 12 kDa reductase, which is a common antioxidant [11].…”

Section: Introductionmentioning

confidence: 99%

Drug D, a Diosgenin Derive, Inhibits L-Arginine-Induced Acute Pancreatitis through Meditating GSDMD in the Endoplasmic Reticulum via the TXNIP/HIF-1α Pathway

et al. 2022

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Acute pancreatitis (AP) is one of the most common causes of hospitalization for gastrointestinal diseases, with high morbidity and mortality. Endoplasmic reticulum stress (ERS) and Gasdermin D (GSDMD) mediate AP, but little is known about their mutual influence on AP. Diosgenin has excellent anti-inflammatory and antioxidant effects. This study investigated whether Diosgenin derivative D (Drug D) inhibits L-arginine-induced acute pancreatitis through meditating GSDMD in the endoplasmic reticulum (ER). Our studies were conducted in a mouse model of L-arginine-induced AP as well as in an in vitro model on mouse pancreatic acinar cells. The GSDMD accumulation in ER was found in this study, which caused ERS of acinar cells. GSDMD inhibitor Disulfiram (DSF) notably decreased the expression of GSDMD in ER and TXNIP/HIF-1α signaling. The molecular docking study indicated that there was a potential interaction between Drug D and GSDMD. Our results showed that Drug D significantly inhibited necrosis of acinar cells dose-dependently, and we also found that Drug D alleviated pancreatic necrosis and systemic inflammation by inhibiting the GSDMD accumulation in the ER of acinar cells via the TXNIP/HIF-1α pathway. Furthermore, the level of p-IRE1α (a marker of ERS) was also down-regulated by Drug D in a dose-dependent manner in AP. We also found that Drug D alleviated TXNIP up-regulation and oxidative stress in AP. Moreover, our results revealed that GSDMD-/- mitigated AP by inhibiting TXNIP/HIF-1α. Therefore, Drug D, which is extracted from Dioscorea zingiberensis, may inhibit L-arginine-induced AP by meditating GSDMD in the ER by the TXNIP /HIF-1α pathway.

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Antioxidant Therapy in Pancreatitis

Cited by 18 publications

References 138 publications

Antioxidant Mitoquinone Alleviates Chronic Pancreatitis via Anti-Fibrotic and Antioxidant Effects

Antioxidant Mitoquinone Alleviates Chronic Pancreatitis via Anti-Fibrotic and Antioxidant Effects

Assessment of the state of the oxidant-antioxidant system and lipid peroxidation in patients with chronic pancreatitis combined with hypothyroidism

Drug D, a Diosgenin Derive, Inhibits L-Arginine-Induced Acute Pancreatitis through Meditating GSDMD in the Endoplasmic Reticulum via the TXNIP/HIF-1α Pathway

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