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Gosha-jinki-gan reduced oxaliplatin-induced hypersensitivity to cold sensation and its effect would be related to suppression of the expression of TRPM8 and TRPA1 in rats.
Anticancer Drugs. 2014 Jan; 25(1):39-43.AD

Abstract

Peripheral neuropathy is a common side effect of the chemotherapeutic agent oxaliplatin (Oxp), and is associated with hypersensitivity to cold sensation in the acute stage. Recently, gosha-jinki-gan (GJG), a Japanese herbal medicine, was reported to improve Oxp-induced cold hypersensitivity. However, the mechanism for this effect was not elucidated. We hypothesized that the effect of GJG on Oxp-induced cold hypersensitivity may be associated with the expression of the transient receptor potential melastatin 8 (TRPM8) and transient receptor potential ankyrin 1 (TRPA1) channels, which are cold-gated ion channels. To assess this hypothesis, we examined alteration of the withdrawal response to cold stimulation following coadministration of GJG and Oxp in rats, and the relationship between this altered withdrawal response and the expression of TRPM8 and TRPA1 mRNA in the dorsal root ganglia (DRG). Assessment of cold hypersensitivity was performed at 4 and 10°C using a cold plate. Compared with Oxp administration alone, coadministration of GJG (oral dose: 1 g/kg/day for 12 days) and Oxp (intraperitoneal dose: 4 mg/kg twice a week) significantly reduced the withdrawal response to cold stimulation. On the 12th day of drug administration, the L4-L6 DRG were removed and the expression of TRPM8 and TRPA1 mRNA was determined using RT-PCR. The expression of TRPM8 and TRPA1 in the DRG of rats that were coadministered GJG and Oxp decreased significantly compared with that in the rats administered Oxp alone. These results suggest that coadministration of GJG may improve Oxp-induced cold hypersensitivity by suppressing the overexpression of TRPM8 and TRPA1 mRNA.

Authors+Show Affiliations

Divisions of aClinical Pharmacokinetics bClinical Pharmacy, Department of Pharmaceutical Sciences, International University of Health and Welfare, Ohtawara, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24052105

Citation

Kato, Yoshinori, et al. "Gosha-jinki-gan Reduced Oxaliplatin-induced Hypersensitivity to Cold Sensation and Its Effect Would Be Related to Suppression of the Expression of TRPM8 and TRPA1 in Rats." Anti-cancer Drugs, vol. 25, no. 1, 2014, pp. 39-43.
Kato Y, Tateai Y, Ohkubo M, et al. Gosha-jinki-gan reduced oxaliplatin-induced hypersensitivity to cold sensation and its effect would be related to suppression of the expression of TRPM8 and TRPA1 in rats. Anticancer Drugs. 2014;25(1):39-43.
Kato, Y., Tateai, Y., Ohkubo, M., Saito, Y., Amagai, S. Y., Kimura, Y. S., Iimura, N., Okada, M., Matsumoto, A., Mano, Y., Hirosawa, I., Ohuchi, K., Tajima, M., Asahi, M., Kotaki, H., & Yamada, H. (2014). Gosha-jinki-gan reduced oxaliplatin-induced hypersensitivity to cold sensation and its effect would be related to suppression of the expression of TRPM8 and TRPA1 in rats. Anti-cancer Drugs, 25(1), 39-43. https://doi.org/10.1097/CAD.0000000000000022
Kato Y, et al. Gosha-jinki-gan Reduced Oxaliplatin-induced Hypersensitivity to Cold Sensation and Its Effect Would Be Related to Suppression of the Expression of TRPM8 and TRPA1 in Rats. Anticancer Drugs. 2014;25(1):39-43. PubMed PMID: 24052105.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gosha-jinki-gan reduced oxaliplatin-induced hypersensitivity to cold sensation and its effect would be related to suppression of the expression of TRPM8 and TRPA1 in rats. AU - Kato,Yoshinori, AU - Tateai,Yoshikazu, AU - Ohkubo,Misao, AU - Saito,Yuka, AU - Amagai,Syun-ya, AU - Kimura,Yu-Suke, AU - Iimura,Naohumi, AU - Okada,Megumi, AU - Matsumoto,Akiko, AU - Mano,Yasunari, AU - Hirosawa,Iori, AU - Ohuchi,Kaori, AU - Tajima,Masataka, AU - Asahi,Mariko, AU - Kotaki,Hajime, AU - Yamada,Harumi, PY - 2013/9/21/entrez PY - 2013/9/21/pubmed PY - 2014/7/16/medline SP - 39 EP - 43 JF - Anti-cancer drugs JO - Anticancer Drugs VL - 25 IS - 1 N2 - Peripheral neuropathy is a common side effect of the chemotherapeutic agent oxaliplatin (Oxp), and is associated with hypersensitivity to cold sensation in the acute stage. Recently, gosha-jinki-gan (GJG), a Japanese herbal medicine, was reported to improve Oxp-induced cold hypersensitivity. However, the mechanism for this effect was not elucidated. We hypothesized that the effect of GJG on Oxp-induced cold hypersensitivity may be associated with the expression of the transient receptor potential melastatin 8 (TRPM8) and transient receptor potential ankyrin 1 (TRPA1) channels, which are cold-gated ion channels. To assess this hypothesis, we examined alteration of the withdrawal response to cold stimulation following coadministration of GJG and Oxp in rats, and the relationship between this altered withdrawal response and the expression of TRPM8 and TRPA1 mRNA in the dorsal root ganglia (DRG). Assessment of cold hypersensitivity was performed at 4 and 10°C using a cold plate. Compared with Oxp administration alone, coadministration of GJG (oral dose: 1 g/kg/day for 12 days) and Oxp (intraperitoneal dose: 4 mg/kg twice a week) significantly reduced the withdrawal response to cold stimulation. On the 12th day of drug administration, the L4-L6 DRG were removed and the expression of TRPM8 and TRPA1 mRNA was determined using RT-PCR. The expression of TRPM8 and TRPA1 in the DRG of rats that were coadministered GJG and Oxp decreased significantly compared with that in the rats administered Oxp alone. These results suggest that coadministration of GJG may improve Oxp-induced cold hypersensitivity by suppressing the overexpression of TRPM8 and TRPA1 mRNA. SN - 1473-5741 UR - https://www.unboundmedicine.com/medline/citation/24052105/Gosha_jinki_gan_reduced_oxaliplatin_induced_hypersensitivity_to_cold_sensation_and_its_effect_would_be_related_to_suppression_of_the_expression_of_TRPM8_and_TRPA1_in_rats_ L2 - https://doi.org/10.1097/CAD.0000000000000022 DB - PRIME DP - Unbound Medicine ER -