title: Protective effects of madecassoside against Doxorubicin induced nephrotoxicity in vivo and in vitro.
abstract: Madecassoside (MA), a triterpenoid saponin isolated from C. asitica, exerts various pharmacological activity including antioxidative and antinflammatory. Doxorubicin (DOX), a common chemotherapeutic drug, has been reported to induce numerous toxic side effects including renal-toxicity. We hypothesized that MA administration may decrease renal-toxicity caused by DOX. In this study, we investigated this hypothesis by introducing MA and DOX into the culture of Human Proximal Tubule Cells HK-2 and mice model. Our in vivo study demonstrated that MA (12 mg/kg), treatment for two weeks attenuated DOX-induced renal injury via protecting renal function, recovering antioxidant enzyme activity, inhibiting Bax, p-ERK1/2, NF-κB p65, iNOS expression and increasing Bcl-2 expression. Similar findings were obtained in our in vitro studies with treatment of DOX and/or MA. Further studies with application of iNOS inhibitor and ERK1/2 kinase inhibitor indicated that the inhibitory effects of MA on DOX-induced apoptosis and inflammation might be mediated by the suppression of the activation of cleaved caspase-3, ERK1/2 pathways, NF-κB p65 and NO production. These results suggest that MA is a promising protective agent for DOX-induced renal toxicity and can be a potential candidate to protect against renal toxicity in DOX-treated cancer patients.
authors.affiliation: School of Biomedical Engineering, Institute for Personalized Medicine, Shanghai Jiao Tong University, Shanghai 200030, China.|School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Zhonghao
authors.initials: Z
authors.lastname: Su
authors.affiliation: School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Ye
authors.affiliation: School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Zhenxia
authors.initials: Z
authors.lastname: Qin
authors.affiliation: School of Biomedical Engineering, Institute for Personalized Medicine, Shanghai Jiao Tong University, Shanghai 200030, China.
authors.forename: Xianting
authors.initials: X
authors.lastname: Ding
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007677:Kidney Function Tests; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009393:Nephritis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D020011:Protective Agents / Q000737:chemistry / Q000494:pharmacology*; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D016328:NF-kappa B; D020011:Protective Agents; D014315:Triterpenes; D009569:Nitric Oxide; D004317:Doxorubicin; C093443:madecassoside