Chronic aristolochic acid toxicity in rabbits: a model of Chinese herbs nephropathy?
BACKGROUND
Chinese herbs nephropathy (CHN) is a new type of subacute interstitial nephritis that is attributed to aristolochic acid (AA), which inadvertently has been included in slimming pills. The contribution of other simultaneously prescribed drugs remains disputed. In the present study, the effects of a chronic intake of AA given as a single drug was evaluated through renal histology and function in rabbits.


METHODS
Female New Zealand White rabbits were injected intraperitoneally with either 0.1 mg AA/kg or with saline 5 days a week for 17 to 21 months. Body weight, renal function, and urinary excretion of glucose and low molecular weight proteins were monitored prior to sacrifice at the end of the study period.


RESULTS
All animals given AA developed renal hypocellular interstitial fibrosis, which was classified into three patterns. Fibrosis was confined to medullary rays (MRs) in pattern I (N = 3), extended to the outer cortical labyrinth (OCL) in pattern II (N = 2), and eventually to the inner cortical labyrinth (ICL) in pattern III (N = 6). Fibrosis in MR and OCL was associated with mainly proximal tubular epithelial cell flattening. All treated animals displayed urothelial atypia. Three of them also developed tumors of the urinary tract. No significant pathologic changes were found in control rabbits. AA-treated animals differed from controls by an impaired growth, increased serum creatinine, glucosuria, tubular proteinuria, and anemia.


CONCLUSIONS
The observed pattern of renal histopathological lesions and disorders of the renal function, as well as urothelial atypia and malignancy, are very reminiscent of CHN. Our observations therefore support a causal role of AA alone in the genesis of this new nephropathy.
Cosyns
J P
JP
Department of Pathology, Public Health School, Université Catholique de Louvain, Medical School, Brussels, Belgium. cosyns@anps.ucl.ac.be
Dehoux
J P
JP
Guiot
Y
Y
Goebbels
R M
RM
Robert
A
A
Bernard
A M
AM
van Ypersele de Strihou
C
C
D000818:Animals; D034341:Aristolochic Acids; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000633:toxicity*; D004791:Enzyme Inhibitors / Q000633:toxicity*; D005260:Female; D005355:Fibrosis; D007668:Kidney / Q000473:pathology; D009395:Nephritis, Interstitial / Q000139:chemically induced* / Q000473:pathology; D009929:Organ Size; D010616:Phenanthrenes / Q000633:toxicity*; D011817:Rabbits; D013270:Stomach / Q000473:pathology
D034341:Aristolochic Acids; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D010616:Phenanthrenes; C000228:aristolochic acid I