The cancer chemotherapeutic agent doxorubicin (DOX), Adriamycin, is part of the treatment regimen for breast, ovarian, small cell lung cancer and acute/chronic lymphoid leukemia. Adverse effects associated with DOX are cardiotoxicity and nephrotoxicity. Interventions are needed to reduce DOX nephrotoxicity. Resveratrol (RES) is a phytochemical contained in grapes, berries and nuts, which possesses antioxidant and anticancer properties. This study tested the hypothesis that RES will attenuate DOX renal cytotoxicity in human noncancerous renal proximal tubular epithelial (HK-2) cells and that RES will reduce DOX mediated changes in mitochondrial function. HK-2 cells were plated and grown for 48 hours (h). Cells were next pre- incubated for 1h with 0 (DMSO), 5 or 7.5 µM RES followed by a 24 h co-incubation with 0–5 µM DOX. RES did not alter cell growth or viability at the concentrations tested as indicated by comparable MTT values between DMSO and RES groups (p > 0.05). Cell viability was further assessed by cell count using Trypan blue exclusion. DOX produced a concentration dependent decline in viability within a 24 h exposure. Pretreatment for 1h with RES was sufficient to reduce DOX loss of cell viability. Studies were initiated to investigate the cellular mechanism of RES attenuation of DOX cytotoxicity. Western blot of cells following 24 h exposure examined increased protein carbonylation as an indicator of oxidative stress. Initial studies were begun to examine the DOX effects on mitochondrial oxygen consumption using a Seahorse platform. In summary, RES did not diminish cell viability at the concentrations tested in our HK-2 cells. DOX diminished cell viability within 24 h relative to vehicle control. A 1 h pretreatment with RES reduced DOX cytotoxicity in HK-2 cells. Prevention of mitochondrial impairment and oxidative stress by DOX are potential mechanisms for RES protection in HK-2 cells.
|Commitee:||Rankin, Gary, Salisbury, Travis|
|School Location:||United States -- West Virginia|
|Source:||MAI 57/04M(E), Masters Abstracts International|
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