Carnosine attenuates cyclophosphamide-induced bone marrow suppression by reducing oxidative DNA damage
Oxidative DNA damage in bone marrow cells is the main side effect of chemotherapy drugs including cyclophosphamide (CTX). However, not all antioxidants are effective in inhibiting oxidative DNA damage. In this study, we report the beneficial effect of carnosine (β-alanyl-l-histidine), a special ant...
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Format: | Article |
Language: | English |
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Elsevier
2018-04-01
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Series: | Redox Biology |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231717305621 |
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doaj-203552a815894321b3be3821e841fb60 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jie Deng Yi-Fei Zhong Yan-Ping Wu Zhuo Luo Yuan-Ming Sun Guo-En Wang Hiroshi Kurihara Yi-Fang Li Rong-Rong He |
spellingShingle |
Jie Deng Yi-Fei Zhong Yan-Ping Wu Zhuo Luo Yuan-Ming Sun Guo-En Wang Hiroshi Kurihara Yi-Fang Li Rong-Rong He Carnosine attenuates cyclophosphamide-induced bone marrow suppression by reducing oxidative DNA damage Redox Biology |
author_facet |
Jie Deng Yi-Fei Zhong Yan-Ping Wu Zhuo Luo Yuan-Ming Sun Guo-En Wang Hiroshi Kurihara Yi-Fang Li Rong-Rong He |
author_sort |
Jie Deng |
title |
Carnosine attenuates cyclophosphamide-induced bone marrow suppression by reducing oxidative DNA damage |
title_short |
Carnosine attenuates cyclophosphamide-induced bone marrow suppression by reducing oxidative DNA damage |
title_full |
Carnosine attenuates cyclophosphamide-induced bone marrow suppression by reducing oxidative DNA damage |
title_fullStr |
Carnosine attenuates cyclophosphamide-induced bone marrow suppression by reducing oxidative DNA damage |
title_full_unstemmed |
Carnosine attenuates cyclophosphamide-induced bone marrow suppression by reducing oxidative DNA damage |
title_sort |
carnosine attenuates cyclophosphamide-induced bone marrow suppression by reducing oxidative dna damage |
publisher |
Elsevier |
series |
Redox Biology |
issn |
2213-2317 |
publishDate |
2018-04-01 |
description |
Oxidative DNA damage in bone marrow cells is the main side effect of chemotherapy drugs including cyclophosphamide (CTX). However, not all antioxidants are effective in inhibiting oxidative DNA damage. In this study, we report the beneficial effect of carnosine (β-alanyl-l-histidine), a special antioxidant with acrolein-sequestering ability, on CTX-induced bone marrow cell suppression. Our results show that carnosine treatment (100 and 200 mg/kg, i.p.) significantly inhibited the generation of reactive oxygen species (ROS) and 8-hydroxy-2â²-deoxyguanosine (8-oxo-dG), and decreased chromosomal abnormalities in the bone marrow cells of mice treated with CTX (20 mg/kg, i.v., 24 h). Furthermore, carnosine evidently mitigated CTX-induced G2/M arrest in murine bone marrow cells, accompanied by reduced ratios of p-Chk1/Chk1 and p-p53/p53 as well as decreased p21 expression. In addition, cell apoptosis caused by CTX was also suppressed by carnosine treatment, as assessed by decreased TUNEL-positive cell counts, down-regulated expressions of Bax and Cyt c, and reduced ratios of cleaved Caspase-3/Caspase-3. These results together suggest that carnosine can protect murine bone marrow cells from CTX-induced DNA damage via its antioxidant activity. Keywords: Carnosine, Cyclophosphamide, Oxidative DNA damage, Sister chromatid exchange, Apoptosis, Cell cycle arrest |
url |
http://www.sciencedirect.com/science/article/pii/S2213231717305621 |
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doaj-203552a815894321b3be3821e841fb602020-11-24T21:56:33ZengElsevierRedox Biology2213-23172018-04-011416Carnosine attenuates cyclophosphamide-induced bone marrow suppression by reducing oxidative DNA damageJie Deng0Yi-Fei Zhong1Yan-Ping Wu2Zhuo Luo3Yuan-Ming Sun4Guo-En Wang5Hiroshi Kurihara6Yi-Fang Li7Rong-Rong He8Anti-stress and Health Research Center, College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, PR China; Institute of Traditional Chinese Medicine & Natural Products, Jinan University, Guangzhou, Guangdong 510632, PR China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou, Guangdong 510632, PR ChinaAnti-stress and Health Research Center, College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, PR China; Institute of Traditional Chinese Medicine & Natural Products, Jinan University, Guangzhou, Guangdong 510632, PR China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou, Guangdong 510632, PR ChinaAnti-stress and Health Research Center, College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, PR China; Institute of Traditional Chinese Medicine & Natural Products, Jinan University, Guangzhou, Guangdong 510632, PR China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou, Guangdong 510632, PR ChinaAnti-stress and Health Research Center, College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, PR China; Institute of Traditional Chinese Medicine & Natural Products, Jinan University, Guangzhou, Guangdong 510632, PR China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou, Guangdong 510632, PR ChinaGuangdong Provincial Key Lab of Food Safety and Quality, South China Agricultural University, Guangzhou, Guangdong 510642, PR ChinaAnti-stress and Health Research Center, College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, PR China; Institute of Traditional Chinese Medicine & Natural Products, Jinan University, Guangzhou, Guangdong 510632, PR China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou, Guangdong 510632, PR ChinaAnti-stress and Health Research Center, College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, PR China; Institute of Traditional Chinese Medicine & Natural Products, Jinan University, Guangzhou, Guangdong 510632, PR China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou, Guangdong 510632, PR ChinaAnti-stress and Health Research Center, College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, PR China; Institute of Traditional Chinese Medicine & Natural Products, Jinan University, Guangzhou, Guangdong 510632, PR China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou, Guangdong 510632, PR China; Corresponding authors at: Anti-stress and Health Research Center, College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, PR ChinaAnti-stress and Health Research Center, College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, PR China; Institute of Traditional Chinese Medicine & Natural Products, Jinan University, Guangzhou, Guangdong 510632, PR China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou, Guangdong 510632, PR China; Corresponding authors at: Anti-stress and Health Research Center, College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, PR ChinaOxidative DNA damage in bone marrow cells is the main side effect of chemotherapy drugs including cyclophosphamide (CTX). However, not all antioxidants are effective in inhibiting oxidative DNA damage. In this study, we report the beneficial effect of carnosine (β-alanyl-l-histidine), a special antioxidant with acrolein-sequestering ability, on CTX-induced bone marrow cell suppression. Our results show that carnosine treatment (100 and 200 mg/kg, i.p.) significantly inhibited the generation of reactive oxygen species (ROS) and 8-hydroxy-2â²-deoxyguanosine (8-oxo-dG), and decreased chromosomal abnormalities in the bone marrow cells of mice treated with CTX (20 mg/kg, i.v., 24 h). Furthermore, carnosine evidently mitigated CTX-induced G2/M arrest in murine bone marrow cells, accompanied by reduced ratios of p-Chk1/Chk1 and p-p53/p53 as well as decreased p21 expression. In addition, cell apoptosis caused by CTX was also suppressed by carnosine treatment, as assessed by decreased TUNEL-positive cell counts, down-regulated expressions of Bax and Cyt c, and reduced ratios of cleaved Caspase-3/Caspase-3. These results together suggest that carnosine can protect murine bone marrow cells from CTX-induced DNA damage via its antioxidant activity. Keywords: Carnosine, Cyclophosphamide, Oxidative DNA damage, Sister chromatid exchange, Apoptosis, Cell cycle arresthttp://www.sciencedirect.com/science/article/pii/S2213231717305621 |