Madecassoside attenuated doxorubicin-induced renal injury and apoptosis by protecting renal function, recovering antioxidant enzyme activity, and suppressing ERK1/2, NF-κB p65, and NO production.
Does madecassoside prevent doxorubicin-induced nephrotoxicity in vitro and in vivo?
Madecassoside demonstrates protective effects against doxorubicin-induced nephrotoxicity in preclinical models, suggesting potential as a renoprotective agent in DOX-treated cancer patients.
p-value: p=<0.05
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.
Su et al. (Mon,) conducted a other in Doxorubicin-induced nephrotoxicity (n=36). Madecassoside vs. Doxorubicin alone was evaluated on Renal toxicity and apoptosis (p=<0.05). Madecassoside attenuated doxorubicin-induced renal injury and apoptosis by protecting renal function, recovering antioxidant enzyme activity, and suppressing ERK1/2, NF-κB p65, and NO production.