Aristolochic acid nephropathy: A model of nephrotoxic lesion

Abstract

Aristolochia clematitis, or birthwort, is a very toxic cancerogenic plant, and is a representative of the genus Aristolochia, whose main toxins are aristolochic acids. The nephrotoxicity of this plant is especially potent. Two important human diseases likely caused by aristolochic acids are Chinese herbal nephropathy and Balkan endemic nephropathy (BEN). In the present study, we used laboratory NMRI mice as an experimental model of nephrotoxic lesions, in order to examine the relation between aristolochic acids and these diseases and to investigate the effect of chronic toxicity caused by A. clematitis infusion. The presence of aristolochic acids in A. clematitis infusions was confirmed by gas chromatography with mass spectrometric detection. Experimental animals were divided into three groups that received different concentration of infusion (10 g/1000 ml, 20 g/1000 ml and 40 g/1000 ml) per os. After 17 weeks of experiment, histological sections of kidneys for all experimental animals displayed characteristic infiltrates around glomeruli with clusters of lymphocytes and plasma cells. Also, changes in tubule parenchyma with visible damage of nephrocytes was observed. These pathological changes represent diffuse interstitial nephritis in the chronic phase of inflammation. The toxic effects of A. clematitis cause changes in kidneys that could manifest as initial stages of chronic diseases such as BEN and Chinese herb nephropathy.