Ethnopharmacological relevance: Xian-ling-gu-bao (XLGB) is a traditional Chinese prescription commonly used to treat osteoporosis, osteoarthritis, aseptic bone necrosis, climacteric syndrome, and bone fracture. However, there is limited toxicological information available on XLGB in preclinical animal model studies. It has also been recently reported that XLGB may be related to liver injury in humans.
Aim of study: This study was designed to determine the potential toxic effects of XLGB, particularly hepatotoxicity, in Sprague-Dawley rats following oral administration for up to 26 weeks.
Materials and methods: Male and female rats were administered XLGB by oral gavage at doses of 0, 100, 300, and 1000 mg/kg for 26 weeks followed by a recovery period of 4 weeks. Clinical signs, body weight, food consumption, ophthalmology, hematology, coagulation, serum chemistry, urinalysis, bone mineral density, hormone concentration, organ weights and histopathology were examined at the end of 13- and 26-week dosing period as well as after the recovery period.
Results: Neither hepatotoxicity nor any other toxic effects were observed in the XLGB treated rats at doses up to 1000 mg/kg for 26 weeks except for a slight increase in the organ weight of the uterus in female rats at doses higher than 300 mg/kg on week 26.
Conclusions: In this study, we found the no-observed-adverse-effect level (NOAEL) for XLGB in Sprague-Dawley rats was 1000 mg/kg, a dose that was equivalent to 3.3 times human dose based on body surface area.
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