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Effect of dimethyl fumarate on rats with chronic pancreatitis
Wen-Xian Zhang1, Jian-Hong Zhao1, Fu-Min Ping1
1Affiliated Hospital of Hebei University of Engineering, Han Dan, Hebei 056002, China.
Objective:
To discuss the effect of dimethyl fumarate (DMF) on rats with l-arginine induced chronic pancreatitis (CP).
Methods:
Male Wistar rats were given DMF treatment (25 mg/kg) by oral lavage method; then Wistar rats were given the intraperitoneal injection of l-arginine for 5 times (250 mg/100 kg, twice per time, each interval of 1 h) for building of CP model. Rats were divided into control group, CP group, DMF group and CP + DMF group. Rats in CP + DMF group were given the oral intragastric administration of DMF (25 mg/kg), while rats in control group and CP group were given the equal volume of normal saline. The weight of rats was evaluated and the intraperitoneal glucose tolerance test was performed (IPGTT, 2 g/kg). The islet of rats was isolated and then flow cytometry was employed to evaluate the quality and activity of islets. Meanwhile, the histology of non-endocrine tissues and levels of myeloperoxidase (MPO) and malondialdehyde (MDA) were detected.
Results:
Compared with control group, the weight of rats in CP group was significantly reduced at week 2, 4 and 6; the blood glucose significantly increased, AUC increased, the histopathological scores of pancreatic atrophy, acinar injury, edema and cellular infiltration increased, levels of MDA and MPO increased, the islet equivalent and islet activity decreased at 0, 30, 60, 120 and 180 min. Compared with CP group, the weight of rats in CP + DMF group significantly increased at week 2, 4 and 6; the blood glucose significantly decreased, AUC decreased, the histopathological scores of pancreatic atrophy, acinar injury, edema and cellular infiltration decreased, levels of MDA and MPO decreased, the islet equivalent and islet activity increased at 0, 30, 60, 120 and 180 min.
Conclusions:
DMF treatment can improve CP induced by l-arginine and islet function in rats.
Insights
Dimethyl fumarate (DMF) treatment improved chronic pancreatitis (CP) in rats. DMF administration mitigated pancreatic damage and enhanced islet function, offering potential therapeutic benefits for CP.
Area of Science:
- Gastroenterology
- Endocrinology
- Pharmacology
Background:
- Chronic pancreatitis (CP) is a progressive inflammatory disease with significant morbidity.
- L-arginine administration in rats is a common model for inducing CP.
- Islet dysfunction is a hallmark of chronic pancreatitis, leading to metabolic complications.
Purpose of the Study:
- To investigate the therapeutic effects of dimethyl fumarate (DMF) on a rat model of l-arginine induced chronic pancreatitis (CP).
- To evaluate the impact of DMF on pancreatic histology, islet function, and oxidative stress markers in CP rats.
Main Methods:
- Male Wistar rats were used to establish a CP model via intraperitoneal injection of l-arginine.
- Rats were divided into control, CP, DMF, and CP + DMF groups.
- DMF treatment (25 mg/kg) was administered orally. Parameters assessed included body weight, glucose tolerance (IPGTT), islet quality and activity (flow cytometry), pancreatic histology, and levels of myeloperoxidase (MPO) and malondialdehyde (MDA).
Main Results:
- CP induction led to reduced body weight, impaired glucose tolerance, increased pancreatic damage scores, elevated MDA and MPO levels, and decreased islet equivalent and activity.
- DMF treatment in CP rats significantly improved body weight, glucose tolerance, and pancreatic histology.
- DMF administration also reduced oxidative stress markers (MDA, MPO) and enhanced islet function (islet equivalent and activity) compared to the CP group.
Conclusions:
- Dimethyl fumarate (DMF) demonstrates significant therapeutic potential in ameliorating l-arginine induced chronic pancreatitis in rats.
- DMF treatment effectively improves pancreatic tissue integrity and restores islet function, suggesting a protective role against CP-associated damage.
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