Oral subacute nephrotoxicity of aristololactam I in rats

Aristolactams (ALs) have been recognized as one kind of metabolites of aristolochic acids (AAs), the nephrotoxic components of Aristolochiaceae plants, and are more widely distributed than AAs in herbal medicines. This study evaluated the oral subacute nephrotoxicity of aristolactam I (AL I), a representative compound of ALs. AL I was intragastrically administered to rats at 20 mg·kg^-1·d^-1 for 10 or 20 days, with aristolochic acid I (AA I) used as positive control at the same dose. After 10-day treatment, AL I led to a significant increase in early renal injury-related indices in urine and obvious histopathological lesions in kidneys, including degeneration of tubular epithelial cells, inflammatory cell infiltration and fibrosis. The lesions induced by AL I were significantly aggravated after 20-day exposure. However, AL I induced less histopathological damage in kidneys than AA I in both 10- and 20-day groups. Our results indicated that oral AL I caused nephrotoxicity by inducing oxidative stress, inflammation, and overactivation of the complement system as AA I did. Three detected apoptosis-associated indicators were not affected by AL I but remarkably increased by AA I. In summary, oral AL I induced evident renal damage in rats after only 10 days of treatment, and the damage was aggravated after 20 days. However, AL I was obviously less nephrotoxic than AA I via oral gavage.