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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 Nephritis Model
Nephritis can be modeled in rats with an intraperitoneal injection of the chemotherapeutic agent Cisplatin.  Acute nephritis is chacterized by altered blood and urine chemistries, as well as histological evidence of kidney tubule damage and inflammatory cell infiltration.  Pre-treatment with DL-propargylclycine (PAG) has been suggested to reduce these markers of injury.  In this study, PAG was tested for effects on Cisplatin-induced changes in blood and urine chemistries, along with histological examination of kideny tissue after treatment.     

Figure 1: Blood Chemistry

                           Blood chemistry in cisplatin challenged rats

Blood chemistry.  Blood chemistry levels in plasma samples from Cisplatin (CP) challenged rats.  On day five of the study, blood plasma samples were collected and analyzed for various markers of kidney function.  Blood nitrogen urea (BUN), Creatine (CRE) and Sodium (Na) were significantly increased after Cisplatin challenged compared to untreated controls.  PAG attenuated the increase in these kidney markers.  Data are mean ± SEM; ***p<0.001 compared to untreated control, #p<0.05 compared to Cisplatin.

 

Figure 2: Urine Chemistry

Urine chemistry levels in cisplatin challenged rats

Urine chemistry.  Urine chemistry levels in plasma samples from Cisplatin (CP) challenged rats.  On day five of the study, twenty-four hour urine samples were collected and analyzed for various markers of kidney function.  Creatine (CRE) was significantly decreased after Cisplatin challenge compared to untreated controls (A).  PAG treatment did not significnatly alter levels of these markers compared to CP-only treated animals. There were no significant changes in total urine protein (B).  Data are mean ± SEM; ***p<0.001 compared to untreated control.

 

Figure 3: Kidney Histology

 

                                                             Kiney histology cisplatin challenged rat

Kiney histology cisplatin challenged rat

Kidney histology. Morphological assessment of kidney tissue from Cisplatin challenged rats.  On day five of the study, kidney samples were collected, fixed and analyzed histologically with H&E staining.  Cisplatin caused a marked pathological response including extensive cell injury in the cortex and outer medulla (B) compared to non-treated controls (A).  Rats treated with PAG (C) displayed significantly less severe pathology compared to cisplatin (CP) alone.  Data are mean ± SEM; ***p<0.001 compared to untreated control, #p<0.05 compared to Cisplatin.

 

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