Acute and Subacute Oral Toxicity Assessment of European Cranberrybush (Viburnum opulus L). Fruit Extract

Abstract

Abstract Objectives The intake of the high dose of polyphenols might cause adverse health effects on humans, in such cases, toxicological testing may be required to ensure safe levels of intake. In the present study, acute and subacute oral toxicity studies of polyphenol-rich European cranberrybush (Viburnum opulus L.) (ECB) fruit extract were evaluated to ensure the safe use of this extract. Methods In acute toxicity, freshly prepared ECB extract dissolved in distilled water was administrated to Sprague-Dawley rats by oral gavage at a single dose of 2000 mg/kg and signs of toxicity and mortality was observed. In subacute toxicity, Balb-c mice were administrated orally at 500 (low dose) and 2000 mg/kg (high dose) of ECB extract for 28 days and their mortality, clinical signs and, body weight were recorded on a daily and weekly basis, respectively. At the end of 28 days, while blood samples from each animal were taken for hematological and biochemical analysis, vital organs were taken for histopathological examination. Results In acute toxicity study, ECB extract showed no toxicological signs observed on behavioral change and body weight of rats after 14 days indicating that the lethal dose (LD50) of the ECB fruit extract might be higher than 2000 mg/kg. No death and no abnormal clinical signs were also recorded in subacute toxicity study. However, the increment in body weight of administrated high dose of ECB extract animals were significantly lower than control (P > 0.05). High dose of ECB fruit extract induced the level of in some hematological parameters. Even amylase and lipase values were lower than normal ranges at high dose animals, other biochemical parameters results were not significantly different from the controls. In histopathological examination, the total histopathological scores ECB extract administrated mice at both doses were showed normal histological features in many tissues compared to control. However, administrated with a high dose of ECB extract showed significant changes in kidney, liver, and adipose tissue that were alterations (edema, infiltration, and bleeding) compared to control. Conclusions These findings indicated that polyphenol-rich ECB extract might show a toxic effect at a high dose (2000 mg/kg) and no observed adverse effect level (NOAEL) of ECB extract was 500 mg/kg ECB fruit juice. Funding Sources This study was supported by Yeditepe University.