Sub-chronic oral toxicity screening of quercetin in mice

Abstract

Background Quercetin is an organic flavonoid present in several fruits and vegetables. The anti-inflammatory, antiviral, antioxidant, cardio-protective, anti-carcinogenic and neuroprotective properties demonstrated by this dietary supplement endorses it as a possible treatment for inflammatory diseases and cancer. Unfortunately, conflicting research has cast uncertainties on the toxicity of quercetin. The main purpose of this study was to determine if quercetin has any toxic properties in mice at doses that have shown efficacy in pre-clinical studies regarding cancer, cancer therapy, and their off-target effects. Methods A sub-chronic toxicity study of quercetin was examined in male and female CD2F1 mice. Three different doses of quercetin (62, 125, and 250 mg/kg of diet) were infused into the AIN-76A purified diet and administered to mice ad libitum for 98 days. Body weight (BW), food consumption, water intake, body composition, blood count, behavior, and metabolic phenotype were assessed at various timepoints during the course of the experiment. Tissue and organs were evaluated for gross pathological changes and plasma was used to measure alkaline phosphatase (AP), aspartate transaminase (AST), and alanine transaminase (ALT). Results We found that low (62 mg/kg of diet), medium (125 mg/kg of diet), and high (250 mg/kg of diet) quercetin feeding had no discernible effect on body composition, organ function, behavior or metabolism. Conclusions In summary, our study establishes that quercetin is safe for use in both female and male CD2F1 mice when given at ~ 12.5, 25, or 50 mg/kg of BW daily doses for 14 weeks (i.e. 98 days). Further studies will need to be conducted to determine any potential toxicity of quercetin following chronic ingestion.

Secondary Metabolites Isolated from Artemisia afra and Artemisia annua and Their Anti-Malarial, Anti-Inflammatory and Immunomodulating Properties—Pharmacokinetics and Pharmacodynamics: A Review

“…However, in a sub-chronic toxicity study carried out by Yao et al [ 124 ], following the daily oral administration of chrysin (1000 mg/kg), the compound significantly decrease body weight, liver weight was increased, there were significant alteration in the hematology, and an LD 50 value of 4350 mg/kg was reported. The results from a sub-chronic toxicity study of quercetin examined in male and female CD2F1 mice administered at 62, 125 and 250 mg/kg indicated that quercetin is safe to CD2F1 mice, as they showed no signs of toxicity, and no changes in hematological and histopathological parameters were observed [ 125 ]. Lucida et al [ 126 ] also confirmed the safety of quercetin in an acute test, with an LD50 value > 1600 mg/kg.…”

Quercetin Improved Muscle Mass and Mitochondrial Content in a Murine Model of Cancer and Chemotherapy-Induced Cachexia

“…In the current study we sought to investigate quercetin’s ability to protect against skeletal muscle mass loss in a novel model of cancer and chemotherapy-induced cachexia. We recently showed quercetin was safe at multiple doses [ 32 ] and now show that quercetin partially preserved muscle mass and protected muscle mitochondrial content and quality control in the context of cancer and chemotherapy.…”

“…We recently conducted a sub-chronic quercetin toxicity study in CD2F1 mice and found that quercetin had no deleterious effects or toxicities at various dosages [ 32 ]. The purpose of the current study was to examine quercetin’s efficacy in preventing cachexia in C26 tumor-bearing mice treated with 5FU.…”

Long Non-Coding RNA Malat1 Increases the Rescuing Effect of Quercetin on TNFα-Impaired Bone Marrow Stem Cell Osteogenesis and Ovariectomy-Induced Osteoporosis

“…Then, a Sham-operation was performed on the mice ( n = 6) or the animals were surgically ovariectomized ( n = 12) under anesthesia. After a week of recovery, the OVX animals were randomly divided into 2 groups: OVX control group and OVX orally administrated with quercetin (50 mg/kg) twice per week following the dosage suggestions from previous studies [ 33 ]. At 4 weeks post treatment, all animals were sacrificed by an overdose of anesthesia and both femurs of the mice were collected and fixed 24 h by 10% neutral formalin solution.…”