Paper Details
- Ikuo Nakamura (Department of Gastroenterological Surgery, Hyogo Medical University, Hyogo / ikuon@hyo-med.ac.jp)
1) Department of Gastroenterological Surgery, Hyogo Medical University, Hyogo , 2) Department of Pharmacy, Shiga University of Medical Science Hospital, Shiga , 3) Tsumura Kampo Research Laboratories, Tsumura & Co., Ibaraki , 4) Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Kyoto , 5) Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto
Lenvatinib has been approved for treating various cancers; however, it exerts numerous adverse effects. Hochuekkito, a Japanese Kampo medicine, can alleviate these adverse effects. Here, we aimed to evaluate the effect of Hochuekkito on lenvatinib-induced chronic fatigue in a murine model. BALB/C mice were fed a control diet or a diet supplemented with 1.5% Hochuekkito for six weeks. On days 15–42, the mice were intraperitoneally injected with dimethyl sulfoxide or lenvatinib. Accordingly, the mice were divided into control/dimethyl sulfoxide, control/lenvatinib, 1.5% Hochuekkito/dimethyl sulfoxide, and 1.5% Hochuekkito/lenvatinib groups. Body weight and food intake were recorded daily. Nesting tests were performed once a week, and the serum interleukin-6 (IL-6) concentration was measured. Liver drug-metabolizing enzyme, CYP3A4, breast cancer resistance protein (BCRP), and P-glycoprotein (P-gp) levels were determined. The serum lenvatinib concentration and CYP3A4, BCRP, and P-gp levels did not differ significantly between the control/lenvatinib and 1.5% Hochuekkito/lenvatinib groups. The usage rate of nesting material on day 42 was higher in the 1.5% Hochuekkito/lenvatinib group than in the control/lenvatinib group (p < 0.05). The serum IL-6 level was lower in the control/dimethyl sulfoxide and 1.5% Hochuekkito/lenvatinib groups than in the control/lenvatinib group (p < 0.05). Overall, Hochuekkito may alleviate lenvatinib-induced fatigue through IL-6 inhibition.
