Acute renal failure (ARF) is a common and potentially life-threatening complication after ischemia/reperfusion and/or exposure to nephrotoxic agents, including cisplatin, gentamicin, NSAID, etc. It is a reversible condition in which there is a sudden decline in renal function, manifested by hourly/daily/weekly elevation in serum creatinine and blood urea nitrogen (BUN). As there is no effective pharmacotherapy for ARF, seeking alternative treatments becomes a necessity. For the discovery and development of novel therapeutics, Creative Biolabs offers various chemically-induced ARF models, including gentamicin-induced ARF rat model, cisplatin-induced mice and rat models, and glycerol-induced rat model.
Human Myoglobinuric ARF
Human myoglobinuric ARF is a uremic syndrome accompanied by skeletal muscle breakdown (rhabdomyolysis) and intracellular elements that are released into the bloodstream. Rhabdomyolysis-induced ARF develops after skeletal muscle trauma related to physical, thermal, ischemic, infective, metabolic, or toxic causes, releasing toxic doses of myoglobin and other intracellular proteins into the circulation. The model for studying this form of ARF is obtained in the rat by intramuscular injection of glycerol.
Fig.1 In Serum creatinine and BUN levels in different froups of glycerol-induced AFR rats
G1: saline; G2: glycerol; G3: glycerol and ATR extract 250 mg/kg; G4: glycerol and ATR extract 500 mg/kg; G5: ATR extract 500 mg/kg. (Rao et al. 2015)
Glycerol-Induced ARF
Glycerol-induced ARF is one of the most commonly used models of experimental ARF in rats and is considered as an experimental analogue of human myoglobinuric ARF that results from transfusion accidents or crush injury. The pathogenic mechanisms of glycerol-induced myoglobinuric ARF involve ischemic injury, tubular nephrotoxicity caused by myoglobin, and the renal actions of cytokines released after rhabdomyolysis.
A standard method of inducing renal failure is by intramuscular administration of 50% glycerol, v/v (8 mL/kg, i.m.), to both hind legs. Consequently, the striated muscle dissolves, the myoglobin, and other potentially toxic intracellular components are released into the systemic circulation. This is by far the most appropriate animal model that clinically mimics the rhabdomyolysis-induced renal failure in humans. Thus, it is widely used for the screening of novel therapeutic agents for nephroprotective activity in order to prevent the toxic effects of commonly used chemical therapeutic agents.
Creative Biolabs provides assessments for preclinical in vivo evaluation of nephroprotective agents including but not limited to:
Meanwhile, Creative Biolabs also offers other types of rodent urological disease models that you may be interested in:
The testing of potential drug candidates for their efficacy evaluation and mechanism of action requires the use of appropriate models. Creative Biolabs is aimed at offering the best-fit preclinical animal models to in various research areas. In addition to the validated models listed above, we also offer turn-key or ala carte services customized to our client's needs if you would like to propose a new model or customize an existing model.
Reference
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