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Doxorubicin Renal Cytotoxicity and Protection by Resveratrol (RES)
Author(s) -
Valentovic Monica,
Getty Morghan,
Brown Katie C.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.562.3
Subject(s) - cytotoxicity , viability assay , doxorubicin , resveratrol , pharmacology , oxidative stress , chemistry , mtt assay , apoptosis , cancer research , biochemistry , medicine , in vitro , chemotherapy
The cancer chemotherapeutic agents Doxorubicin (DOX, Adriamycin), is part of the treatment regimen for breast, Hodgkin and Non‐Hodgkin lymphomas, small cell lung cancer and acute lymphoid leukemia. Doxorubicin clinical usage is associated with cardiomyopathy and renal impairment. The mechanism for doxorubicin mediated renal toxicity has remained elusive. Resveratrol (RES) is a phytoalexin found in many fruits including grapes, blueberries, chocolate and peanuts. Antioxidant and anticancer properties have been reported for RES in cell culture and in vivo. This study tested the hypothesis that RES will reduce DOX renal cytotoxicity in human noncancerous renal proximal tubular epithelial cells (HK‐2) and that RES will attenuate DOX cytotoxicity by preserving mitochondrial function and reducing oxidative stress. HK‐2 cells were grown for 48 h. Cells were next pre‐incubated for 1 h with 0 (DMSO) or 5 or 7.5 uM RES followed by a 24 h co‐incubation with 0–5 uM DOX. All results were obtained from 3 independent experiments. Western analysis probed for protein carbonylation was used as an indicator of oxidative stress. Mitochondrial function was assessed using a Seahorse XFp system. Prior to examining mitochondrial function, cell number and substrate concentrations were optimized based on the manufacturer's recommendations. Mitochondrial Stress Test was conducted following the treatments described above and each well was normalized to protein. Western blot was conducted on whole cell lysate for SIRT1 and PGC1alpha. Viability was assessed using MTT leakage. RES did not alter cell viability as indicated by comparable MTT values between DMSO and RES groups (p>0.05). DOX was cytotoxic to HK‐2 cells within 24 h. Pretreatment with RES provided protection from DOX to HK‐2 cells. Mitochondrial respiration assessed as oxygen consumption rate (OCR) was diminished by DOX. DOX impaired mitochondria function within 24 h and RES provided protection. Further studies are needed to better characterize DOX mediated changes in mitochondria and reversal by RES. Support or Funding Information (Supported by NIH Grant P20GM103434 to the West Virginia IDeA Network for Biomedical Research Excellence). This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .