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A. Pandit
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P1.02 - Biology/Pathology (ID 614)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.02-003 - Prevention of Adriamycin-induced Cardiac Damage by NAD-ModulationPrevention of Adriamycin-induced Cardiac Damage by NAD-Modulation (ID 9137)
09:30 - 09:30 | Author(s): A. Pandit
- Abstract
Background:
Adriamycin (ADR), a potent anticancer chemotherapeutic agent, is used to treat a variety of human neoplasms. However, its clinical use is hampered by severe side effects including cardiotoxicity. It has been reported that ADR-induced cardiotoxicity is related to myocardial oxidative stress, disruption of cellular and mitochondrial Ca[2+] homeostasis and DNA damage. Nevertheless, the remedy for ADR cardiotoxicity is still not developed. Here we describe the effect of NAD[+]/NADH modulation by NQO1 enzymatic action on ADR-induced cardiotoxicity in mice.
Method:
C57BL/6 male mice were intraperitoneally injected with ADR. Before and after exposure to ADR, the mice were orally administrated with WK0202, a substrate of NQO1, (20 mg/kg body weight of mice). Cardiac biomarkers (CPK, Trop I, LDH and SGOT) in plasma levels, oxidative biomarkers and mRNA levels of pro-inflammatory cytokines were determined to compare cardiac toxicity of each experimental group.C57BL/6 male mice were intraperitoneally injected with ADR. Before and after exposure to ADR, the mice were orally administrated with WK0202, a substrate of NQO1, (20 mg/kg body weight of mice). Cardiac biomarkers (CPK, Trop I, LDH and SGOT) in plasma levels, oxidative biomarkers and mRNA levels of pro-inflammatory cytokines were determined to compare cardiac toxicity of each experimental group.
Result:
Cardiac biomarkers in sera, oxidative biomarkers, and mRNA levels of pro-inflammatory cytokines were significantly increased in ADR-treated mice. However, these increases were significantly alleviated by WK0202. We also demonstrated that the downfall in SIRT1 and SIRT3 activities is critically involved in ADR-induced cardiotoxicity through acetylation of NF-κB p65 and p53. However, increase of NAD[+]/NADH by WK0202 through NQO1 enzymatic action attenuated ADR-induced cardiotoxicity through recovery of SIRT1 and SIRT3 activities and subsequent deacetylation of NF-κB p65 and p53. .
Conclusion:
WK0202 has a protective effect against ADR-induced acute cardiotoxicity through NQO1 enzymatic action. Therefore, WK0202 might be a new therapeutic option for preventing chemotherapy-associated side effects.
