Persistent renal injury following short-term oral administration of Aristolochia species in mice

Abstract

The use of medicinal plants is widespread, with approximately 20,000 species identified by the World Health Organization. In Brazil, the National Health Surveillance Agency officially recognizes 67 plant species for use in traditional therapies, such as infusions and decoctions. Among these, Aristolochia triangularis and Aristolochia brasiliensis are traditionally employed, mainly for the treatment of rheumatism, gout, and arthritis, due to their purported analgesic, anti-inflammatory, and diuretic properties. However, the nephrotoxic potential of these species is not well documented in the scientific literature. In this study, we evaluated renal toxic effects induced by decoctions prepared from the dried stems of these species administered orally to Swiss mice for seven days. Histomorphometric, immunohistochemical (caspase-3), and biochemical analyses were performed at three time points: 1, 21, and 35 days post-exposure. Our findings revealed persistent renal injury, including inflammatory infiltration, cellular vacuolization, pyknotic nuclei, glomerular degradation, and elevated apoptosis. The histopathological alteration index indicated severe lesions at all evaluated time points. Crucially, these structural damages were corroborated by a severe and delayed deterioration of renal function. Serum creatinine, blood urea nitrogen, and the urinary albumin-to-creatinine ratio showed significant progressive increases, reaching peak levels at 35 days. This study is among the first to demonstrate that short-term exposure can cause prolonged nephrotoxic damage. These findings raise concerns regarding the safety of the traditional use of these Aristolochia species and provide experimental evidence relevant to the assessment of their nephrotoxic potential.