Differential Organ Distribution of 7-(Deoxyadenosin-N6-yl)-aristolactam I in Mice Exposed to Aristolochic Acid I: Insights from Acute and Chronic Exposure Studies.

The distribution of 7-(deoxyadenosin-N6-yl)-aristolactam I (ALI-dA) in mice treated with the same amount of aristolochic acid I (AA-I) at different dosage rates was investigated. The results showed a distinct organ distribution pattern of ALI-dA, with the highest adduct levels observed in the bladders of mice that received chronic doses of AA-I. In contrast, in mice that received AA-I acutely, the highest levels were found in the kidneys and were over ten times higher than those observed with chronic exposure. These results indicate that, in addition to the cumulative dose, the rate at which humans are exposed to AA-I is an under-recognized risk factor in the development of aristolochic acid nephropathy.