engleski

Proteomic Investigation into the toxicity of aristolochic acid

Ingestion of extracts from Aristolochia species is associated with the development of a progressive renal disease designated Aristolochic acid Nephropathy (AAN). AAN is characterized by chronic renal failure, tubulointerstitial fibrosis and aventually by urothelial cancer. Aristolochia extracts contain a mixture of structurally similar components, the most abundant being aristolochic acid I(AA I)and aristolochic acid II(AA II). In animal studies both AA I and AA II have been shown to form DNA adducts and are mutagenic ( genotoxic). However, nephrotoxicity is only associated with exposure to AA I. We followed specific alternations to the kidney proteome in sensitive mice after tratment with AA I and AA II. Quantitative differene in proteome of treated and non-treated animals was determined by MS/MS after iTRAQ labeling. Proteins identified in the urine of AA I, and AA II treated mice serve as candidate biomarkers for the diagnosis of AAN. It could be shown that the iTRAQ MS/MS and quatitation is reliable and reproducible method for determining relative protein levels in complex samples such as whole cell lysates.

Aristolochic acid; nephropathy; kidney proteome

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