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We previously reported that a pathological protein interaction between TRPC3 channels and NADPH oxidase 2 (Nox2) contributed to doxorubicin\u2010induced cardiac atrophy in mice. Here we have investigated the effects of ibudilast, a drug already approved for clinical use and known to block doxorubicin\u2010induced cytotoxicity, on the TRPC3\u2010Nox2 complex. We specifically sought evidence that this drug attenuated doxorubicin\u2010induced systemic tissue wasting in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>We used the RAW264.7 macrophage cell line to screen 1,271 clinically approved chemical compounds, evaluating functional interactions between TRPC3 channels and Nox2, by measuring Nox2 protein stability and ROS production, with and without exposure to doxorubicin. In male C57BL\/6 mice, samples of cardiac and gastrocnemius muscle were taken and analysed with morphometric, immunohistochemical, RT\u2010PCR and western blot methods. In the passive smoking model, cells were exposed to DMEM containing cigarette sidestream smoke.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Ibudilast, an anti\u2010asthmatic drug, attenuated ROS\u2010mediated muscle toxicity induced by doxorubicin treatment or passive smoking, by inhibiting the functional interactions between TRPC3 channels and Nox2, without reducing TRPC3 channel activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>These results indicate a common mechanism underlying induction of systemic tissue wasting by doxorubicin. They also suggest that ibudilast could be repurposed to prevent muscle toxicity caused by anticancer drugs or passive smoking.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14777","type":"journal-article","created":{"date-parts":[[2019,6,26]],"date-time":"2019-06-26T11:39:45Z","timestamp":1561549185000},"page":"3723-3738","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Ibudilast attenuates doxorubicin\u2010induced cytotoxicity by suppressing formation of TRPC3 channel and NADPH oxidase 2 protein complexes"],"prefix":"10.1111","volume":"176","author":[{"given":"Kazuhiro","family":"Nishiyama","sequence":"first","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takuro","family":"Numaga\u2010Tomita","sequence":"additional","affiliation":[{"name":"National Institute for Physiological Sciences (NIPS), National 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