[Injury in renal proximal tubular epithelial cells induced by aristololactam I].
OBJECTIVE
To study whether aristololactam I (AL-I) induces injury in human renal proximal tubular epithelial cells.


METHODS
Cultured human renal proximal tubular epithelial cell line HK-2 was used as the subject. Aristolochic Acid I (AA-I) was used as a positive control. Cell toxicity of AL-I was detected by LDH releasing rate. Cell apoptosis was evaluated by cellular morphology, DNA content and expression of cell membrane phosphatidylserine (PS). The secretion level of fibronectin (FN) and TGF-beta1 in HK-2 cells were assayed by ELISA.


RESULTS
AL-I had a direct toxicity on HK-2 in a dose dependent manner from 2.5 mg x mL(-1) to 20 mg x mL(-1); In these range of concentration, AL-I could induce cell apoptosis which was detectable by measurements of morphology, DNA content and expression of PS. AL-I could stimulate the secretion of FN and TGF-beta1. The potency of AL-I cell toxicity was higher than AA-I at the same concentration. The effects of AL-I on apoptosis, secretion of FN and TGF-beta1 were all weaker than AA-I.


CONCLUSIONS
AL-I as one metabolite of AA-I in vivo induces direct injury in renal proximal tubular cells. Its effects are similar to those of AA-I. AL-I may be one of toxic metabolites in Chinese herbs containing AA which participate in renal damage and fibrosis.
Li
Biao
B
Renal Division, Department of Medicine, First Hospital, Peking University, Beijing 100034, China.
Li
Xiao-mei
XM
Zhang
Cui-ying
CY
Wang
Xuan
X
Cai
Shao-qing
SQ
D017209:Apoptosis / Q000187:drug effects*; D030022:Aristolochia / Q000737:chemistry; D034341:Aristolochic Acids / Q000008:administration & dosage / Q000302:isolation & purification / Q000633:toxicity*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004247:DNA / Q000235:genetics; D004171:Diploidy; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000378:metabolism; D010946:Plants, Medicinal / Q000737:chemistry
D034341:Aristolochic Acids; C121135:aristolactam I; D004247:DNA; C000228:aristolochic acid I