Abstract
The present study investigated the effects of quercetin on cisplatin (CDDP)-induced common side effect, myelosuppression, and the possible mechanisms in Balb/c mice. The mice were randomly treated with CDDP alone or in combination with quercetin for 14 days. Quercetin was given by intraperitoneal injection (10 mg/kg, 3 times a week; IQ) or by a diet containing 0.1% or 1% quercetin (LQ and HQ, respectively). We found that quercetin supplementation especially HQ and IQ, significantly restored the decrease in number of bone marrow cells, total white blood cells, red blood cells and platelets, and the body weight in mice exposed to CDDP (p ≤ 0.05). Similar trends were observed in the number of neutrophils, lymphocytes and monocytes in the plasma. HQ and IQ also increased the levels of hematopoietic growth factors (HGFs), especially in granulocyte-macrophage-colony stimulating factor and IL-9 (p < 0.05), but decreased the levels of hematopoietic inhibitory factors (HIFs) and oxidative stress in the plasma and the bone marrow in CDDP-exposed mice. Furthermore, both quercetin and quercetin-3-O-glucuronide (Q3G) significantly increase cell viability and inhibited apoptosis at 48 or 72 h (p ≤ 0.05), accompanied by increasing HGF levels and decreasing HIF levels in the cultured medium in 32D cells exposed to CDDP. IL-9 siRNA transfection suppressed the effects of quercetin and Q3G on cell viability (p ≤ 0.05) in32D cells. In conclusion, our results indicate that quercetin attenuates CDDP-induced myelosuppression through the mechanisms associated with regulation of HGFs and HIFs.
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