Oral exposure to aristolochic acid I induces gastric histological lesions with non-specific renal injury in rat

Many Aristolochia species herbal drugs, used for diseases treatment since antiquity, contain active component aristolochic acid mixture, which consists of aristolochic acid I and II. However, it remains unclear whether aristolochic acid I is gastrotoxic, though evidence has shown that aristolochic acid mixture is nephrotoxic, carcinogenic, and genotoxic. The present study aimed to investigate the gastrotoxicity in rats treated with aristolochic acid I alone. Four groups of rats were orally administrated with vehicle (1% NaHCO3), or 30 mg, 60 mg, and 90 mg/kg/day of aristolochic acid I for twelve days. The results showed that aristolochic acid I can induce obvious body weight loss, forestomach injury characterized by necrosis, ulcer, hyperkeratosis, and hyperplasia of epithelial cells. The severity of these forestomach lesions was presented in a dose-dependent mode. Meanwhile, only non-specific, slight renal tubule degeneration, and occasionally single necrotic epithelial cell were found in aristolochic acid I-treated rats’ kidney. These resulst indicated aristolochic acid I had obvious gastrotoxicity, and such aristolochic acid I-induced forestomach toxicity probably presented much prior to kidney injury. Such irritation lesions may play a partial role in gastric cancer development of rats induced by aristolochic acid. Therefore, these results expanded our understanding on the digestive system toxicity of aristolochic acid I.