melior melior discovery melior pharmaceuticals preclinical services pre-clinical services in vivo pharmacology in vivo efficacy efficacy models pharmacokinetics indications discovery specialized animal models bioanalytical services theratrace exton pennsylvania cro contract research drug discovery drug development metabolic disease alzheimer’s alzheimers diabetes reprofiling
Melior Discovery
home
Therapeutic Areas
Safety Assessment
 


theraTRACE

Melior Pharmaceuticals

melior melior melior discovery melior pharmaceuticals preclinical services pre-clinical services in vivo pharmacology in vivo efficacy efficacy models pharmacokinetics indications discovery specialized animal models bioanalytical services theratrace exton pennsylvania cro contract research drug discovery drug development metabolic disease alzheimer’s alzheimers diabetes reprofiling

Melior Discovery inflammation/arthritis

Acute Pancreatitis Model
Pancreatic injury can be modeled in mice with multiple peritoneal injections of Caerulein.  This acute pancreatitis is characterized by increased serum amylase and pancreatic myeloperoxidase (MPO), as well as histological evidence of alveolar thickening and inflammatory cell infiltration.  Pre-treatment with DL-Propargylglycine (PAG) has been suggested to reduce these markers of injury.  In this study, PAG was tested for effects on Caerulein-induced increases in serum amylase and pancreatinc MPO, along with histological examination of pancreas tissue after treatment.   

Figure 1: Myeloperoxidase levels in pancreatic tissue 

                           Myeloperoxidase levels in pancreatic tissue

Myeloperoxidase levels in pancreatic tissue.  CD-1 mice were treated with vehicle, Caerulein or Caerulein + PAG.  One hour after final Caerulein injection, pancreas samples were collected, homogenized and analyzed for MPO levels via ELISA.  Caerulein significantly increased MPO levels in the pancreas, while Cer+PAG treated mice had significantly attenuated MPO levels compared to vehicle (untreated) mice.  Data are mean ± SEM; *p<0.05 compared to vehicle (untreated control); #p<0.05 compared to Caerulein.

 

Figure 2: Serum Amylase

                                     Serum amylase in caerulein challenged mice

Serum Amylase.  Amylase levels in serum from Caerulein-challenged mice.  CD-1 mice were treated with vehicle, Caerulein or Caerulein+PAG.  One hour after final injection, blood samples were collected and serum was isolated and analyzed for amylase levels by enzymatic assay.  Amylase was significantly increased after Caeruein treatement compared to vehicle (nontreated). PAG pre-treatment did not significantly alter the increase in serum amylase compared to Caerulein alone.  Data are mean ± SEM; ***p<0.05 compared to vehicle (untreated control).

 

Multiple injections of Caerulein in mice caused significant acute pancreatitis, as measured by increases in serum amylase and pancreatic MPO.  The Caerulein dosing was well-tolerated, with no observable adverse effects.  Pre-treatment with PAG significantly reduced levels of MPO, but did not alter amylase levels in the challenge model.  These results demonstrated that Caerulein injections are sufficient to induce a measurable acute pancreatitis model that can be moderately altered by PAG pre-treatment.  This model has potential utility in screening therapeutic compounds for treatment of pancreatitis.

 

if you are interested in learning more about the Acute Pancreatitis Model, please contact models@meliordiscovery.com to start the conversation.