NAD(+) administration decreases doxorubicin-induced liver damage of mice by enhancing antioxidation capacity and decreasing DNA damage.

Abstract

One of the major obstacles for cancer treatment is the toxic side effects of anti-cancer drugs. Doxorubicin (DOX) is one of the most widely used anti-cancer drugs, which produces significant toxic side effects on the heart and such organs as the liver. Because NAD(+) can decrease cellular or tissue damage under multiple conditions, we hypothesized that NAD(+) administration may decrease DOX-induced hepatotoxicity. In this study we tested this hypothesis by using a mouse model, showing that NAD(+) administration can significantly attenuate DOX-induced increase in serum glutamate oxaloacetate transaminase activity and decrease in liver weight. The NAD(+) administration also attenuated the DOX-induced increases in the levels of double-strand DNA (dsDNA) damage, TUNEL signals, and active caspase-3. Furthermore, our data has suggested that the NAD(+) administration could produce protective effects at least partially by restoring the antioxidation capacity of the liver, because NAD(+) administration can attenuate the decreases in both the GSH levels and the glutathione reductase activity of the DOX-treated liver, which could play a significant role in the DOX-induced hepatotoxicity. This finding has provided the first evidence indicating that NAD(+) is capable of increasing the antioxidation capacity of tissues. Collectively, our study has found that NAD(+) can significantly decrease DOX-induced liver damage at least partially by enhancing antioxidation capacity and decreasing dsDNA damage. Because it can also selectively decrease tumor cell survival, NAD(+) may have significant merits over antioxidants for applying jointly with DOX to decrease the toxic side effects of DOX.

• Authors: Ban Wang, Yingxin Ma, Xiaoni Kong, Xianting Ding, Hongchen Gu, Tianqing Chu, Weihai Ying
• Journal: Chemico-biological interactions (Chem Biol Interact) Vol. 212 Pg. 65-71 (Apr 05 2014) ISSN: 1872-7786 [Electronic] Ireland
• PMID: 24491677 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Antioxidants
• NAD
• Doxorubicin
• Aspartate Aminotransferases
• Acetylcysteine

Topics

• Acetylcysteine (administration & dosage, pharmacology)
• Animals
• Antineoplastic Agents (adverse effects)
• Antioxidants (metabolism)
• Apoptosis (drug effects)
• Aspartate Aminotransferases (blood)
• Body Weight (drug effects)
• Cytoprotection (drug effects)
• DNA Damage
• Doxorubicin (adverse effects)
• Liver (anatomy & histology, cytology, drug effects, metabolism)
• Male
• Mice
• Mice, Inbred ICR
• NAD (administration & dosage, metabolism, pharmacology)
• Organ Size (drug effects)