[Observation of penetration, distribution and accumulation in human renal proximal tubular epithelial cells by aristololactam-I].
OBJECTIVE
To study whether aristololactam I (AL-I) can enter renal proximal tubular epithelial cells and the situation of intracellular distribution and accumulation.


METHODS
Cultured human renal proximal tubular epithelial cell line (HK-2) was used as the subject. Intracellular fluorescence from AL-I and its distribution are examined by fluorescence microscopy after a treatment with different concentration of AL-I, the intracellular accumulation of AL-I was also investigated by incubated cells in AL-I -free medium for 48 h after washing-out the media containing AL-I.


RESULTS
After treatment of AL-I (concentration from 5 microg x mL(-1) to 20 microg x mL(-1)), glaucous fluorescence could be observed inside renal proximal tubular epithelial cells at 0.5 h, and the fluorescence distributed only in cytoplasm while not be observed in nuclei. Moreover, the fluorescence of AL-I could be kept in cytoplasm for more than 48 h after washing out the media containing AL-I .


CONCLUSIONS
AL-I is able to enter renal proximal tubular epithelial cells in short time and accumulate in cytoplasm, but not enter nuclei. This property may contribute to the cytotoxic mechanism of renal injury induced by AL-I, which may partially explain the persistent renal toxicity of AAs and its metabolites in the development of aristolochic acid nephropathy.
Shang
Pu
P
School of Pharmaceutical Sciences, Peking University, Beijing 100083, China.
Wang
Xuan
X
Li
Xiao-Mei
XM
Tang
Jia-Wei
JW
Cai
Shao-Qing
SQ
D000818:Animals; D034341:Aristolochic Acids / Q000378:metabolism* / Q000633:toxicity; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000473:pathology; D008856:Microscopy, Fluorescence
D034341:Aristolochic Acids; C540320:aristololactam-I; C000228:aristolochic acid I