H Y Yang1, X H Zheng, Y Du, Z Chen, D Y Zhu, Y J Lou. 1. Institute of Pharmacology, Toxicology and Biochemical Pharmaceutics, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Aristolochic acid I (AAI), a major component derived from Aristolochia species, which have been known for a long time and remain in use today, particularly in Asia and Central America. It has been confirmed to induce a type of so-called aristolochic acid nephropathy (AAN) and involved in the development of Balkan endemic nephropathy (BEN). AIM OF THE STUDY: To investigate the kinetic of AAI in beagle dogs after single-dose oral administration of Radix Aristolochiae or its preparation, Guanxinsuhe, as well as the effects of compound compatibility in traditional Chinese medicine on the pathologic processes of AAN. MATERIALS AND METHODS: Beagle dogs were orally administrated Radix Aristolochiae (0.3 g/kg/day), Guanxinsuhe preparation (0.9 g/kg/day) (with an identical dosage of AAI), and empty capsules respectively for 180 days. Canines (n=2) were euthanized on day 90, 180, 210, HPLC was established to determine the AAI level in plasma and the kinetic behaviors of AAI in dogs were elucidated after single dosing. Hematoxylin and eosin (H&E)-staining was applied for histopathologic examination to evaluate the pathological status of kidneys. RESULTS: Compared to canines with Radix Aristolochiae treatment, the Cmax, AUC, Tmax, and t(1/2β) of AAI in Guanxinsuhe preparation group were elevated, while t(1/2α) of AAI was decreased. The results indicated the co-existing components in Guanxinsuhe preparation could increase the absorption, accelerate the distribution, but delay the absorption and elimination of AAI. After long-term dosing, animals treated with Radix Aristolochiae were found with more severe renal impairment and higher AAI level in plasma. CONCLUSIONS: It was demonstrated that the compound compatibility in Guanxinsuhe preparation can affect the kinetic process of AAI and attenuate the toxic effect on kidney when the duration of treatment was prolonged.
ETHNOPHARMACOLOGICAL RELEVANCE: Aristolochic acid I (AAI), a major component derived from Aristolochia species, which have been known for a long time and remain in use today, particularly in Asia and Central America. It has been confirmed to induce a type of so-called aristolochic acidnephropathy (AAN) and involved in the development of Balkan endemic nephropathy (BEN). AIM OF THE STUDY: To investigate the kinetic of AAI in beagle dogs after single-dose oral administration of Radix Aristolochiae or its preparation, Guanxinsuhe, as well as the effects of compound compatibility in traditional Chinese medicine on the pathologic processes of AAN. MATERIALS AND METHODS:Beagle dogs were orally administrated Radix Aristolochiae (0.3 g/kg/day), Guanxinsuhe preparation (0.9 g/kg/day) (with an identical dosage of AAI), and empty capsules respectively for 180 days. Canines (n=2) were euthanized on day 90, 180, 210, HPLC was established to determine the AAI level in plasma and the kinetic behaviors of AAI in dogs were elucidated after single dosing. Hematoxylin and eosin (H&E)-staining was applied for histopathologic examination to evaluate the pathological status of kidneys. RESULTS: Compared to canines with Radix Aristolochiae treatment, the Cmax, AUC, Tmax, and t(1/2β) of AAI in Guanxinsuhe preparation group were elevated, while t(1/2α) of AAI was decreased. The results indicated the co-existing components in Guanxinsuhe preparation could increase the absorption, accelerate the distribution, but delay the absorption and elimination of AAI. After long-term dosing, animals treated with Radix Aristolochiae were found with more severe renal impairment and higher AAI level in plasma. CONCLUSIONS: It was demonstrated that the compound compatibility in Guanxinsuhe preparation can affect the kinetic process of AAI and attenuate the toxic effect on kidney when the duration of treatment was prolonged.