Acute and sub-chronic oral toxicity studies of hesperidin isolated from orange peel extract in Sprague Dawley rats

Abstract

Citrus sinensis contains glycoside hesperetin-7-rhamnoglucoside (hesperidin) which harbor an array of therapeutic potentials including antioxidant, anticancer, and anti-inflammatory. However, a systematic examination of safety is needed before its utilization. Hence, the present investigation is aimed to evaluate acute and sub-chronic toxicity of hesperidin isolated from the citrus fruit. Hesperidin (73%) was isolated from a methanolic extract of dried peel of the citrus fruit, characterized using FTIR, and standardized by HPLC. Its acute oral toxicity (AOT) and sub-chronic toxicity studies were carried out in Sprague-Dawley rats. Hesperidin (5000 mg/kg) showed 10% mortality in AOT. In sub-chronic toxicity study, hesperidin (250 and 500 mg/kg) did not induce any abnormalities in body weight, food consumption, clinical signs, ophthalmological and neurological observations, urine analysis, hematology, clinical chemistry, organ weights, and gross pathology. However, hesperidin (1000 mg/kg) showed significant (p < 0.05) alterations in body and organ weights, hematology, clinical chemistry, and tissue histopathology. To conclude, hesperidin has median lethal dose (LD₅₀) of 4837.5 mg/kg, and Low Observed Adverse Effect Level (LOAEL) at 1000 mg/kg for both male and female Sprague-Dawley rats. Thus, hesperidin isolated from citrus fruit showed a good safety profile in animal study.

Keywords: Acute toxicity test; Hesperidin; LD(50); OECD; Orange peel; Sub-chronic toxicity tests.