A variety of exogenous (mainly drugs) or endogenous toxins cause acute kidney injury (AKI) in humans and in experimental animals. Thus, this property of drugs/toxin is utilized by investigators to induce disease models for clinical research of potential drugs as well as to study the pathogenesis of toxicity. Particularly, Creative Biolabs provides an acute renal failure (ARF) model induced by gentamicin, which is among the most common causes of AKI, to evaluate in vivo nephroprotective activity of potential compounds.

AKI Caused by Gentamicin

AKI is a major kidney disease characterized by rapid loss of renal function, resulting in accumulation of metabolic waste and imbalanced electrolytes and bodily fluid. Aminoglycoside antibiotics are used for the treatment of many severe infections. Gentamicin is a commonly used aminoglycoside antibiotic which is effective for the treatment of most gram-negative microorganism infections in humans. However, the prescription of aminoglycoside is limited because of its nephrotoxicity, even at therapeutic doses. It has been reported that 30% of patients treated with gentamicin for more than 7 d show signs of nephrotoxicity. At present, GM-induced nephrotoxicity is among the most common causes of acute renal failure and promotes both increased morbidity and greater health care costs.

Fig. 1 Images of TUNEL staining in the kidney tubules, kidney glomeruli, and collecting tubulesFig. 1 Evaluation of cell apoptosis in each group using TUNEL staining.1

The Pathogenesis of Gentamicin Nephrotoxicity

The pathogenesis of gentamicin-induced kidney failure has not fully been clarified yet. Studies show that the specificity of gentamicin-induced renal toxicity is related to its preferential accumulation in the renal convoluted tubules and lysosomes. Other factors that contribute to the pathogenesis of gentamicin nephrotoxicity include alteration of mitochondrial respiration, generation of superoxide anion and hydroxyl radicals, reduction of antioxidant defense mechanisms, depletion of reduced glutathione, Na+-K+-ATPase inhibition, opening of mitochondrial permeability transition pore and activation of the renin-angiotensin system.

Gentamicin-induced AKI Model

Experimental models are important tools used to get a better understanding of the mechanisms involved in renal injury and also for developing optimal management of this pathological condition. Specifically, gentamicin-induced nephrotoxicity model is mostly used to evaluate in vivo nephroprotective activity of natural compounds. Nephrotoxicity induced by gentamicin is a complex situation characterized by an increase in blood urea nitrogen (BUN) and serum creatinine concentration, and tubular necrosis. Therefore, Creative Biolabs provides assessments for in vivo drug efficacy evaluation including but not limited to:

  • Body Weight
  • Kidney Weight
  • Serum Biochemical Parameters
  • Urinary Protein Analysis
  • Histopathological Examinations
  • Immunohistochemistry

Meanwhile, Creative Biolabs also offers other types of rodent urological disease models that you might be interested in:

Creative Biolabs is specialized in the urological area and we are willing to use this expertise to assist you in assessing your test agent's therapeutic potential against AKI, chronic kidney disease, glomerulonephritis, and cystitis. Furthermore, we also offer customized solutions to our clients. Please feel free to contact us for information on the models described above or if you would like to propose a new model or customize an existing model to meet your particular research needs.

Reference

  1. Liu, Pengfei, et al. "Administration of BMSCs with muscone in rats with gentamicin-induced AKI improves their therapeutic efficacy." PloS One 9.5 (2014): e97123. doi: 10.1371/journal.pone.0097123. Distributed under Open Access license CC BY 4.0. The image was modified by extracting and using part of the original image.

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