Korean J Intern Med.  2018 Jul;33(4):763-773. 10.3904/kjim.2016.097.

Effects of aristolochic acid I and/or hypokalemia on tubular damage in C57BL/6 rat with aristolochic acid nephropathy

Affiliations
  • 1Department of Internal Medicine, Hanyang University Guri Hospital, Guri, Korea. cardion@hanyang.ac.kr
  • 2Department of Anatomy, College of Medicine, The Catholic University of Korea, Seoul, Korea.
  • 3Department of Pathology, Konyang University Hospital, Daejeon, Korea.

Abstract

BACKGROUND/AIMS
This study was designed to investigate the roles of aristolochic acid I (AA-I) and hypokalemia in acute aristolochic acid nephropathy (AAN).
METHODS
After an adaptation period (1 week), a total of 40 C57BL/6 mice (male, 8 weeks old) were divided into four groups: I (control group), II (low potassium [K] diet), III (normal K diet with administration of AA-I [10 mg/kg weight]), and IV (low K diet with AA-I). After collecting 24 hours of urine at 2 weeks, the mice were sacrificed, and their blood and kidneys were obtained to perform immunochemical staining and/or Western blot analysis.
RESULTS
Proteinuria, glycosuria, and increased fractional excretion of sodium and K were prominent in groups III and IV (p < 0.05). Diffuse swelling and poor staining of collecting duct epithelial cells were evident in the medullas of group II. Typical lesions of toxic acute tubular injury were prominent in the cortices of groups III and IV. Α-Smooth muscle actin (α-SMA) was higher in the cortices of the mice in groups III and IV versus group II (p < 0.05), and higher in the medullas of group IV than groups I and III (p < 0.05). E-cadherin was higher in the cortices of groups III and IV compared to group I (p < 0.05). The F4/80 value was higher in the cortices and medullas of groups II, III, and IV compared to group I (p < 0.05), particularly in the case of group II.
CONCLUSIONS
AA-I can induce acquired Fanconi syndrome in the acute stage of AAN. Macrophages appear to play a key role in the pathogenesis of AAN and hypokalemic nephropathy. It remains uncertain whether hypokalemia plays any role in AAN and hypokalemia.

Keyword

Aristolochic acid I; Balkan nephropathy; Hypokalemia; Macrophages

MeSH Terms

Actins
Animals
Balkan Nephropathy
Blotting, Western
Cadherins
Diet
Epithelial Cells
Fanconi Syndrome
Glycosuria
Hypokalemia*
Kidney
Macrophages
Mice
Potassium
Proteinuria
Rats*
Sodium
Actins
Cadherins
Potassium
Sodium
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