No abstract

Mitochondrial dysfunction plays an important role in brain aging and has emerged to be an early event in Alzheimer's disease (AD), contributing to neurodegeneration and the loss of physical abilities seen in patients suffering from this disease. We examined mitochondrial dysfunction in a cell culture model of AD (PC12APPsw cells) releasing very low amyloid-β (Aβ40) levels and thus mimicking early AD stages. Our data show that these cells have impaired energy metabolism, low ATP levels, and decreased endogenous mitochondrial respiration. Furthermore, protein levels of PGC1α as well as of Mitofusin 1 were decreased. PC12APPsw cells also showed increased mitochondrial content, probably due to an attempt to compensate the impaired mitochondrial function. Recent data showed that stabilized rice bran extract (RBE) protects from mitochondrial dysfunction in vivo Pharmacol Res. (2013) 76C, 17-27. To assess the effect of RBE on mitochondrial function, we treated PC12APPsw cells for 24 h with RBE. Key components of RBE are oryzanols, tocopherols, and tocotrienols, all substances that have been found to exert beneficial effects on mitochondrial function. RBE incubation elevated ATP production and respiratory rates as well as PGC1α protein levels in PC12APPsw cells, thus improving the impaired mitochondrial function assessed in our cell culture AD model. Therefore, RBE represents to be a promising nutraceutical for the prevention of AD.

Doxorubicin (DOX) is widely used in combination cocktails for treatment of childhood hematologic cancers and solid tumors. A major factor limiting DOX usage is DOX-induced cardiotoxicity. Dexrazoxane (DXR) is an iron-binding compound and the only approved cardioprotectant for use with DOX. Amifostine (AMF) is a free radical scavenger and approved as a broad-spectrum cytoprotectant. We have shown that when female rats are treated with AMF, AMF + DOX, or AMF + DXR + DOX there is a significant decrease in the right femoral and lumbar vertebral bone mineral density (BMD) (P < 0.05) but not in the left femoral BMD. Furthermore, the relative bone volume (BV/TV) was significantly smaller in the lumbar vertebral bodies of rats treated with AMF (21.1%), AMF + DOX (34.4%), and AMF + DXR + DOX (38.4%), as was the trabecular number (Tb.N) with AMF (15.5%), AMF + DOX (29.9%), and AMF + DXR + DOX (32.3%). AMF + DOX- and AMF + DXR + DOX-treated vertebrae also exhibited deterioration in the microarchitecture of the trabecular bone and spinous processes as ascertained by microcomputerized tomography (micro CT). This information will be useful in designing better cancer combination therapies that do not lead to bone deterioration.