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Nontoxic heat shock protein coinducer BRX-220 protects against acute pancreatitis in rats
Zoltán Rakonczay1, Béla Iványi, Ilona Varga
1First Department of Medicine, University of Szeged, Hungary. raz@in1st.szote.u-szeged.hu
Background:
Nontoxic heat shock protein (HSP) inducer compounds open up promising therapeutic possibilities by activating one of the natural and highly conserved defense mechanisms of the organism.
Aims:
In the present experiments, we examined the effects of a HSP coinducer drug-candidate, BRX-220, on the cholecystokinin-octapeptide (CCK)-induced acute pancreatitis in rats.
Methods:
Male Wistar rats weighing 240 to 270 g were divided into two groups. In group B, 20 mg/kg BRX-220 was administered orally, followed by 75 microg/kg CCK subcutaneously three times, after 1, 3, and 5 h. This whole procedure was repeated for 5 d. The animals in group slashed circleB received physiological saline orally instead of BRX-220, but otherwise the protocol was the same as in group B. The rats were exsanguinated through the abdominal aorta 12 h after the last administration of CCK. We determined the serum amylase activity, the plasma trypsinogen activation peptide concentration, the pancreatic weight/body weight ratio, the DNA and total protein contents of the pancreas, the levels of pancreatic HSP60 and HSP72, the activities of pancreatic amylase, lipase, trypsinogen, and free radical scavenger enzymes (superoxide dismutase, catalase, and glutathione peroxidase), the degree of lipid peroxidation, protein oxidation, and the reduced glutathione level. Histopathological investigation of the pancreas was also performed in all cases.
Results:
Repeated CCK treatment resulted in the typical laboratory and morphological changes of experimentally induced pancreatitis. The pancreatic levels of HSP60 and HSP72 were significantly increased in the animals treated with BRX-220. In group B, the pancreatic total protein content and the amylase and trypsinogen activities were significantly higher vs. group slashed circleB. The plasma trypsinogen activation peptide concentration, and the pancreatic lipid peroxidation, protein oxidation, and the activity of Cu/Zn-superoxide dismutase were significantly decreased in group B vs. group slashed circleB, whereas the glutathione peroxidase activity was increased. The morphological damage in group B was significantly lower than that in group slashed circleB.
Conclusion:
The HSP coinducer BRX-220, administered for 5 d, has a protective effect against CCK-induced acute pancreatitis.
Insights
The heat shock protein (HSP) coinducer BRX-220 demonstrated a protective effect against cholecystokinin-octapeptide (CCK)-induced acute pancreatitis in rats. This therapeutic approach enhances the body's natural defense mechanisms against this condition.
Area of Science:
- Biochemistry
- Pharmacology
- Cellular Biology
Background:
- Heat shock protein (HSP) inducers offer therapeutic potential by activating intrinsic cellular defense mechanisms.
- Nontoxic HSP inducers are being explored for their ability to mitigate various disease states.
Purpose of the Study:
- To investigate the efficacy of the HSP coinducer BRX-220 in a rat model of acute pancreatitis.
- To evaluate the protective effects of BRX-220 against cholecystokinin-octapeptide (CCK)-induced pancreatic injury.
Main Methods:
- Male Wistar rats were administered BRX-220 or saline orally for 5 days, followed by subcutaneous CCK injections.
- Pancreatic tissue and serum were analyzed for biochemical markers, including amylase, trypsinogen, HSP60/72 levels, oxidative stress markers, and enzyme activities.
- Histopathological examination assessed the morphological damage of the pancreas.
Main Results:
- BRX-220 treatment significantly increased pancreatic HSP60 and HSP72 levels.
- Animals treated with BRX-220 showed reduced markers of pancreatitis, including lower plasma trypsinogen activation peptide concentration and decreased lipid peroxidation and protein oxidation.
- BRX-220 administration resulted in significantly lower morphological damage in the pancreas compared to controls.
Conclusions:
- The HSP coinducer BRX-220 exhibits a significant protective effect against CCK-induced acute pancreatitis in rats.
- BRX-220 treatment modulated key biochemical and histopathological indicators of pancreatic injury, suggesting therapeutic promise.
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