Assessment of nephrotoxicity of herbal medicine containing aristolochic acid in mice

Background/Aims: It is undetermined if herbal medicines (HM) containing aristolochic acid (AA)-containing have similar nephrotoxicity to AA itself. Methods: We administered HM containing a high concentration of AA for 5 days (short-term study) or a low concentration of AA for 30 days (long-term study) to C57BL/6 mice; for comparison, same dose of AA compound was used as controls. Results: The nephrotoxicity in the HM-and AA-treated mice was compared in terms of renal function, histopathology, oxidative stress, apoptotic cell death, and mitochondrial damage. Short-term HM treatment resulted in acute kidney injury (marked renal dysfunction, acute tubular necrosis, and neutrophil gelatinase-as-sociated lipocalin [NGAL] expression) in which the severity of renal dysfunction and histopathology was comparable with that induced by the administration of AA alone. Long-term HM treatment resulted in features of chronic kidney disease (CKD, mild renal dysfunction and tubular atrophy and dilatation). No significant differences in these parameters were observed between the HM-and AA-treated mice. HM-induced oxidative stress (8-hydroxy-2’-deoxyguanosine and manga-nese-dependent superoxide dismutase expression) and apoptotic cell death (ter-minal deoxynucleotidyl transferase dUTP nick end labelling [TUNEL]-positive cells and active caspase-3 expression) were similar in HM-and AA-treated mice in the short-term and long-term studies. Mitochondrial injury, evaluated by electron microscopy, was also similar in HM-and AA-treated mice in the short-term and long-term studies. Conclusions: The nephrotoxic potential of HM containing AA was similar to that of AA itself.