Polyphenol Contents in Grape-Seed Extracts Correlate with Antipica Effects in Cisplatin-Treated Rats

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Abstract
Background: Grape-seed (Vitis spp.) extract (GSE) is a widely used antioxidant dietary supplement. Chemotherapeutic agents such as cisplatin induce oxidative damage in the gastrointestinal tract and cause nausea and vomiting. Materials and methods: A rat model of simulated emesis was used to observe that cisplatin significantly increased kaolin consumption (or pica). Three GSEs from different sources were used in this study. Results: High-performance liquid chromatographic analysis of five major constituents (gallic acid, catechin, epicatechi, procyanidin B2, and epicatechin gallate) revealed that each constituent had different levels in the three GSEs. Extract #1, prepared in the laboratory of the investigators, had the lowest total polyphenol content (27.27 mg/g); Extract #2, obtained from a dietary supplement company in the United States, had a somewhat higher level (35.84 mg/g); and Extract #3, obtained from China, had the highest level (194.21 mg/g). Subsequently these GSEs were intraperitoneally administered in rats to evaluate their ability to decreasing cisplatininduced pica. At 10 mg/kg all three GSEs, with varying degrees of effect, decreased cisplatin-induced pica. The areas under the curves of kaolin intake from time 0 to 72 hours, compared to those in the cisplantin-only group, were reduced 45% for Extract #1 (p < 0.01), 54% for Extract #2 (p < 0.01), and 66% Extract #3 (p < 0.001). Conclusions: The study data showed variable polyphenol contents and proportions in the three GSEs correlated to variable pharmacologic effects, indicating the importance of standardization of herbal product preparations. However further increasing of the GSE doses reversed the antipica effects of GSEs, probably because of their pro-oxidant effects. Results from this study suggest that an appropriate dose of GSE has therapeutic value in treating cisplatin-induced emesis.