Aristolochic acid I determine the phenotype and activation of macrophages in acute and chronic kidney disease

Sci Rep. 2018 Aug 15;8(1):12169. doi: 10.1038/s41598-018-30628-x.

Abstract

Acute and chronic kidney injuries are multifactorial traits that involve various risk factors. Experimental animal models are crucial to unravel important aspects of injury and its pathophysiological mechanisms. Translating knowledge obtained from experimental approaches into clinically useful information is difficult; therefore, significant attention needs to be paid to experimental procedures that mimic human disease. Herein, we compared aristolochic acid I (AAI) acute and chronic kidney injury model with unilateral ischemic-reperfusion injury (uIRI), cisplatin (CP)- or folic acid (FA)-induced renal damage. The administration of AAI showed significant changes in serum creatinine and BUN upon CKD. The number of neutrophils and macrophages were highly increased as well as AAI-induced CKD characterized by loss of tubular epithelial cells and fibrosis. The in vitro and in vivo data indicated that macrophages play an important role in the pathogenesis of AA-induced nephropathy (AAN) associated with an excessive macrophage accumulation and an alternative activated macrophage phenotype. Taken together, we conclude that AA-induced injury represents a suitable and relatively easy model to induce acute and chronic kidney injury. Moreover, our data indicate that this model is appropriate and superior to study detailed questions associated with renal macrophage phenotypes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / pathology
  • Animals
  • Aristolochic Acids / metabolism*
  • Aristolochic Acids / physiology
  • Cisplatin / pharmacology
  • Disease Models, Animal
  • Female
  • Fibrosis
  • Folic Acid / pharmacology
  • Kidney / pathology
  • Kidney Diseases / metabolism*
  • Kidney Diseases / physiopathology
  • Macrophage Activation / physiology*
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Phenotype
  • Renal Insufficiency, Chronic / metabolism
  • Renal Insufficiency, Chronic / physiopathology

Substances

  • Aristolochic Acids
  • Folic Acid
  • aristolochic acid I
  • Cisplatin