The newest article of Shanghai institute of materia medica analyses disease mechanism
Researchers from Shanghai institute of biological sciences, Chinese academy of sciences and Shanghai institute of materia medica have made new progress in the study of the mechanism of aristolochic acid nephropathy (AAN), which provides important data for the in-depth study of the pathogenesis of aristolochic acid nephropathy (AAN) and the prevention of aristolochic acid nephropathy. The report, published in the Toxicol Sci, an influential journal in the field of toxicology.
The corresponding authors are Ren Jin, a researcher at the Shanghai institute of materia medica, and gong likun, an associate researcher. His research group focuses on the use of advanced technology to screen new safe drugs and establish a standard drug safety assessment system.
Aristolochic acid (AA) is aristolochic acid nephropathy (aristolochic acid nephropathy, AAN) and Balkan endemic nephropathy (Balkan endemic nephropathy, BEN) causes, has caused the world attaches great importance to. Oxidation and reduction are essential metabolic processes for the rapid clearance of AAI (the main toxic component of AA) in different species. However, it is not clear which enzymes are involved in the oxidative and reductive metabolism of AAI in vivo and the role of this metabolic process in AAI nephrotoxicity.
Previous studies conducted by the drug safety evaluation center of Shanghai institute of materia medica showed that liver CYP1A was involved in the oxidative metabolism of AAI, which reduced the AAI content in the blood and kidney of mice and then reduced the renal toxicity caused by AAI. The study has been published in Kidney Int(2008,73:1231-1239).
The kidney is not only the organ with the strongest ability of reducing metabolism AAI, but also the target organ of AAI toxicity. Therefore, based on the previous research work, the researchers further explored which enzyme participates in the reductive metabolism of kidney AAI and the effect of this metabolic process on the renal toxicity of AAI. The results showed that NAD(P)H: quinone oxidoreductase (NQO1) had higher activity in kidney, and its distribution was the same as that of kidney caused by AAI.
The kidney's inhibitors, bicoumarin and benindone, inhibit the reductive metabolism of AAI in kidney, delaying the plasma clearance of AAI. Although the content of AAI in the blood and kidney of mice increased significantly after treatment with inhibitor, the kidney toxicity caused by it decreased significantly, indicating that NQO1 participated in the reductive metabolism of AAI in kidney, and this reductive metabolism process may be the main reason for the kidney toxicity induced by AAI. This result provides a new basis for the in-depth study of AAN mechanism, a new clue for the prevention of aristolochic acid nephropathy, and a new idea for the safety study of traditional Chinese medicine.
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