The HSP coinducer Arimoclomol (BRX-220), administered for 5 d, has a protective effect against CCK-induced acute pancreatitis. Repeated CCK treatment results in the typical laboratory and morphological changes of experimentally induced pancreatitis. The pancreatic levels of HSP60 and HSP72 are significantly increased in the animals treated with Arimoclomol [1]. Arimoclomol is a coinducer of heat shock proteins for the potential treatment of amyotrophic lateral sclerosis (ALS), the most common form of motor neuron disease[2].
In Vitro
Kinase Assay
Cell Assay
Animal Administration
Rats[1] Male Wistar rats weighing 240-270 g are used. The animals are kept at a constant room temperature of 25°C with a 12 h light-dark cycle, and are allowed free access to water and standard laboratory chow. The rats are fasted 18 h before the end of the experiment. In group B (n=6), 20 mg/kg Arimoclomol (BRX-220) is administered intragastrically, followed by 75 μg/kg CCK subcutaneously three times, after 1, 3, and 5 h. This whole procedure is repeated for 5 d. The animals in group AB (n=6) receive physiological saline intragastrically instead of Arimoclomol, but otherwise the protocol is the same as in group B. The animals are sacrificed by exsanguination through the abdominal aorta 12 h after the last CCK injection. Three untreated rats (A) are killed for HSP60 and 72 determinations. The pancreas is quickly removed, cleaned from fat and lymph nodes, weighed, and frozen at -70°C until use[1].
References
[1]. Rakonczay Z Jr, et al. Nontoxic heat shock protein coinducer BRX-220 protects against acute pancreatitis in rats. Free Radic Biol Med. 2002 Jun 15;32(12):1283-92.
[2]. Phukan J. Arimoclomol, a coinducer of heat shock proteins for the potential treatment of amyotrophic lateral sclerosis. IDrugs. 2010 Jul;13(7):482-96.
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