Carnosine attenuates cyclophosphamide-induced bone marrow suppression by reducing oxidative DNA damage.
Carnosine attenuates cyclophosphamide-induced bone marrow suppression by reducing oxidative DNA damage.
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肌肽通过减少氧化 DNA 损伤来减轻环磷酰胺诱导的骨髓抑制。
DOI：
10.1016/j.redox.2017.08.003
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发表时间：
2018-04
期刊：
影响因子：
11.4
通讯作者：
He RR
中科院分区：
文献类型：
--
作者：
Deng J;Zhong YF;Wu YP;Luo Z;Sun YM;Wang GE;Kurihara H;Li YF;He RR
骨髓细胞DNA氧化损伤是包括环磷酰胺(CTX)在内的化疗药物的主要副作用。然而，并不是所有的抗氧化剂都能有效地抑制DNA氧化损伤。在本研究中，我们报道了一种具有丙烯醛隔离能力的特殊抗氧化剂肌肽(β-丙氨酰-L-组氨酸)对环磷酰胺诱导的骨髓细胞抑制的有利作用。我们的结果表明，肌肽处理(100和200 mg/kg，i.p.)能显著抑制环磷酰胺(20 mg/kg，静脉注射，24小时)小鼠骨髓细胞中活性氧(ROS)和8-羟基-2‘-脱氧鸟苷(8-oxo-DG)的生成，减少染色体畸变率。此外，肌肽明显减轻CTX诱导的小鼠骨髓细胞G2/M期阻滞，并伴有p-Chk1/Chk1和p-p53/p53比值降低以及p21表达降低。此外，肌肽治疗也抑制了CTX诱导的细胞凋亡，表现为TUNEL阳性细胞计数减少，Bax和Cytc表达下调，Caspase-3/Caspase-3裂解比率降低。这些结果表明，肌肽可以通过其抗氧化活性来保护小鼠骨髓细胞免受CTX诱导的DNA损伤。CTX诱导的骨髓细胞抑制与ROS增加和DNA氧化损伤有关。肌肽可减轻环磷酰胺引起的DNA氧化损伤和骨髓细胞抑制。肌肽联合环磷酰胺具有良好的临床应用前景。
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-2′-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. Bone marrow cells suppression induced by CTX is associated with the increasement of ROS and oxidative DNA damage. Carnosine attenuates CTX-elevated oxidative DNA damage and bone marrow cells suppression. Favorable prospects of clinical applications for carnosine in combination with CTX.
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影响因子：
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作者：
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DOI：
10.1073/pnas.1119396109
发表时间：
2012-02-21
影响因子：
11.1
作者：
Glen, Colin D.;Dubrova, Yuri E.
通讯作者：
Dubrova, Yuri E.