Mitochondrial DNA Damage Induced by Aristolochic Acid I: Recognizing the Heart as a Target Organ.

We revealed in this study that prolonged aristolochic acid I (AA-I) exposure leads to an increase in oxidative stress level, and decreases in mitochondrial DNA (mtDNA) copy numbers and ATP levels in the heart, kidneys, and liver of exposed mice. The most significant decreases in ATP levels were observed in the heart and kidneys, both of which are high-energy-consuming organs. Additionally, high levels of AA-DNA adducts were detected in the mtDNA isolated from the kidneys. These combined observations of AA-induced mitochondrial dysfunction in key energy-consuming organs may help explain previous observations of rapidly progressive renal failure and the later onset of milder hypertension in patients with aristolochic acid nephropathy.