Effects of aristolochic acid I and/or hypokalemia on tubular damage in C57BL/6 rat with aristolochic acid nephropathy.
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 &lt; 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 &lt; 0.05), and higher in the medullas of group IV than groups I and III (p &lt; 0.05). E-cadherin was higher in the cortices of groups III and IV compared to group I (p &lt; 0.05). The F4/80 value was higher in the cortices and medullas of groups II, III, and IV compared to group I (p &lt; 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.
['Yi|Joo-Hark|JH|', 'Han|Sang-Woong|SW|', 'Kim|Wan-Young|WY|', 'Kim|Jin|J|', 'Park|Moon-Hyang|MH|']
D000818:Animals D034341:Aristolochic Acids D004195:Disease Models, Animal D007008:Hypokalemia D007674:Kidney Diseases D007684:Kidney Tubules D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D056910:Republic of Korea
Aristolochic acid I Hypokalemia Macrophages Balkan nephropathy