Thesis (Ph.D.)--Chulalongkorn University, 2012

In searching for the safe and effective compounds to be used as chemoprotective agents to cease toxicity of doxorubicin on renal cells, plaunotol which is a major constituent in Croton stellatopilosus Ohba extract was studied for its possible effect. The results showed that plaunotol exhibited the protection against doxorubicin-induced cell death in human proximal tubule cells. Treatment of the renal cells with doxorubicin resulted in the significant decrease of cell viability, mainly due to the cause of apoptosis. Pretreatment of the cells with plaunotol for at least 9 h prior doxorubicin exposure rendered cell survival against the toxicity of doxorubicin. In terms of mechanism, plaunotol was shown to up-regulate the level of anti-apoptotic Mcl-1. It was clearly showed that the decrease of Mcl-1 level after doxorubicin treatment was closely associated with the toxic action of the drug, and the pretreatment of plaunotol caused the increase of Mcl-1 was able to prevent the doxorubicin-induced cell death. Furthermore, it was found that the lowering of Mcl-1 was closely related to the presence of reactive oxygen species (ROS). Pretreatment of an antioxidant and plaunotol appeared to retrieve the Mcl-1 level from ROS-induced diminution. Antioxidant activity of plaunotol in human renal cells was clearly observed after the incubation with plaunotol for 3 h. The reduction of ROS in the cells appeared to come from the increase of cellular glutathione which was induced by plaunotol treatment. These results suggest that the nephroprotective effect of plaunotol is a result from its antioxidant activity which in turn preserves the level of anti-apoptotic Mcl-1 protein.