The mechanism of the nephrotoxicity of Aristolochia Manshriensis Kom and Long Dan Xie Gan decoction

We previously demonstrated that two kinds of water abstract of Aristolochia Manshriensis Kom (AMK) and the Long Dan Xie Gan decoction(LDXGD) which is a traditional Chinese medicinal formula containing AMK could induce significant renal injury in rats, and LDXGD caused less severe damage . The aim of this study was to determine the possible mechanism of the renal toxicity of AMK and LDXGD by measuring interleukin‐1β(IL‐1β), interleukin‐6(IL‐6), and angiotensin□ (Ang□) in renal homogenate, and immunohistochemistry for nuclear facter kappa B p56 (NF‐κB p56). SD rats were randomly divided into control, AMK and LDXGD groups (n = 10 per group) and administrated orally for 8 weeks with distilled water, AMK (6g/kg/d) and LDXGD (17.5g/kg/d, containing AMK 6g/kg/d), respectively. Our results demonstrated that (1) IL‐1β, IL‐6,and Ang□ levels in renal homogenate were significantly increased, the expressions of NF‐κB p56 in nephric tubule was significantly augmented in AMK or LDXGD groups, compared with controls. (2) Compared with AMK group, IL‐6, and Ang□ levels were not changed significantly in LDXGD group, however, IL‐1β level decreased, the expressions of NF‐κB p56 was weaked . These results suggest that one possible molecular mechanism underlying the nephrotoxicity of AMK and LDXGD may be related to the regulation of mediators of inflammation by Ang□ or NF‐κB p56, in the other hand, the lower degree of nephrotoxicity of LDXGD compared to AMK may be relevant to the decreased activation of NF‐κB p56 by some herbs in LDXGD excluding AMK, accordingly, the level of mediators of inflammation in downstream decreased .