Full Text:   <3236>

Summary:  <2098>

CLC number: R698+.2

On-line Access: 2015-09-05

Received: 2015-01-15

Revision Accepted: 2015-05-05

Crosschecked: 2015-08-10

Cited: 5

Clicked: 5194

Citations:  Bibtex RefMan EndNote GB/T7714


Bin Zhu


-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2015 Vol.16 No.9 P.780-787


Protective effect of L-carnitine in cyclophosphamide-induced germ cell apoptosis

Author(s):  Bin Zhu, Yan-fei Zheng, Yue-ying Zhang, Yun-song Cao, Lei Zhang, Xin-gang Li, Teng Liu, Zhao-zhu Jiao, Qi Wang, Zhi-gang Zhao

Affiliation(s):  1Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China; more

Corresponding email(s):   1022zzg@sina.com

Key Words:  L-Carnitine, Infertility, Cyclophosphamide, LC3, Beclin-1

Bin Zhu, Yan-fei Zheng, Yue-ying Zhang, Yun-song Cao, Lei Zhang, Xin-gang Li, Teng Liu, Zhao-zhu Jiao, Qi Wang, Zhi-gang Zhao. Protective effect of L-carnitine in cyclophosphamide-induced germ cell apoptosis[J]. Journal of Zhejiang University Science B, 2015, 16(9): 780-787.

@article{title="Protective effect of L-carnitine in cyclophosphamide-induced germ cell apoptosis",
author="Bin Zhu, Yan-fei Zheng, Yue-ying Zhang, Yun-song Cao, Lei Zhang, Xin-gang Li, Teng Liu, Zhao-zhu Jiao, Qi Wang, Zhi-gang Zhao",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Protective effect of L-carnitine in cyclophosphamide-induced germ cell apoptosis
%A Bin Zhu
%A Yan-fei Zheng
%A Yue-ying Zhang
%A Yun-song Cao
%A Lei Zhang
%A Xin-gang Li
%A Teng Liu
%A Zhao-zhu Jiao
%A Qi Wang
%A Zhi-gang Zhao
%J Journal of Zhejiang University SCIENCE B
%V 16
%N 9
%P 780-787
%@ 1673-1581
%D 2015
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1500015

T1 - Protective effect of L-carnitine in cyclophosphamide-induced germ cell apoptosis
A1 - Bin Zhu
A1 - Yan-fei Zheng
A1 - Yue-ying Zhang
A1 - Yun-song Cao
A1 - Lei Zhang
A1 - Xin-gang Li
A1 - Teng Liu
A1 - Zhao-zhu Jiao
A1 - Qi Wang
A1 - Zhi-gang Zhao
J0 - Journal of Zhejiang University Science B
VL - 16
IS - 9
SP - 780
EP - 787
%@ 1673-1581
Y1 - 2015
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1500015

cyclophosphamide (CP) is a widely used anti-cancer agent; however, it can also induce serious male infertility. There are currently no effective drugs to alleviate this side-effect. L-Carnitine has been used to treat male infertility, but whether it can be used to protect against CP-induced male infertility is still unclear. This study aims to explore the effect and mechanism of L-Carnitine in male infertility induced by CP. CP was used to establish an animal model. After three weeks of treatment, rats were sacrificed and testis and serum were harvested for further evaluation. Testosterone and estrogen levels were measured by enzyme-linked immunosorbent assay (ELISA). Testicular injury was examined by hematoxylin and eosin (H & E) staining, and germ-cell apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). The expression of LC3 and beclin-1 was examined by immunohistochemistry, Western blot, and real-time polymerase chain reaction (PCR), respectively. Compared with the CP group, L-Carnitine significantly increases sperm motility, viability, and testosterone level (P<0.05). Western blot and real-time PCR results showed that L-Carnitine treatment can significantly up-regulate the LC3-II and beclin-1 expression in the CP+L-Carnitine group when compared with the control group (P<0.05). In addition, TUNEL-positive cells were also more numerous in the CP group; however, L-Carnitine can effectively retard cell apoptosis in the CP+ L-Carnitine group. In conclusion, L-Carnitine contributes to the inhibition of cell apoptosis and the modulation of autophagy in protecting CP-induced testicular injury. These results suggest the applicability of L-Carnitine in the treatment of male infertility.


方法:采用环磷酰胺诱导大鼠不育模型成功后,给予左卡尼汀治疗15天,然后处死全部大鼠。检测血清中的睾酮和雌激素含量;采用全自动精子分析仪检测附睾组织中精子的数量和质量;采用苏木精-伊红(H & E)染色观察睾丸组织的病理损伤;通过末端脱氧核苷酸转移酶介导的 d UTP缺口标记技术(TUNEL)的染色观察睾丸组织中生精细胞的凋亡;采用免疫组织化学法观察睾丸组织中LC3和Beclin-1的表达;采用蛋白质免疫印迹分析(Western blot)和多聚酶链式反应(PCR)分别检测组织中LC3和Beclin-1的表达。


Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]Aghaei, S., Nikzad, H., Taghizadeh, M., et al., 2014. Protective effect of pumpkin seed extract on sperm characteristics, biochemical parameters and epididymal histology in adult male rats treated with cyclophosphamide. Andrologia, 46(8):927-935.

[2]Aliabadi, E., Karimi, F., Rasti, M., et al., 2013. Effects of L-carnitine and pentoxifylline on the activity of lactate dehydrogenase C4 isozyme and motility of testicular spermatozoa in mice. J. Reprod. Infertil., 14(2):56-61.

[3]Banihani, S., Agarwal, A., Sharma, R., et al., 2014. Cryoprotective effect of L-carnitine on motility, vitality and DNA oxidation of human spermatozoa. Andrologia, 46(6):637-641.

[4]Choi, A.M., Ryter, S.W., Levine, B., 2013. Autophagy in human health and disease. N. Engl. J. Med., 368(7):651-662.

[5]Comish, P.B., Drumond, A.L., Kinnell, H.L., et al., 2014. Fetal cyclophosphamide exposure induces testicular cancer and reduced spermatogenesis and ovarian follicle numbers in mice. PLoS ONE, 9(4):e93311.

[6]Demirdag, K., Bahcecioglu, I.H., Ozercan, I.H., et al., 2004. Role of L-carnitine in the prevention of acute liver damage induced by carbon tetrachloride in rats. J. Gastroenterol. Hepatol., 19(3):333-338.

[7]Hinton, B.T., Snoswell, A.M., Setchell, B.P., 1979. The concentration of carnitine in the luminal fluid of the testis and epididymis of the rat and some other mammals. J. Reprod. Fertil., 56(1):105-111.

[8]Jiang, P., Mizushima, N., 2014. Autophagy and human diseases. Cell Res., 24(1):69-79.

[9]Kanter, M., Topcu-Tarladacalisir, Y., Parlar, S., 2010. Antiapoptotic effect of L-carnitine on testicular irradiation in rats. J. Mol. Histol., 41(2-3):121-128.

[10]Kim, W., Kim, S.H., Park, S.K., et al., 2012. Astragalus membranaceus ameliorates reproductive toxicity induced by cyclophosphamide in male mice. Phytother. Res., 26(9):1418-1421.

[11]Koeth, R.A., Wang, Z., Levison, B.S., et al., 2013. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat. Med., 19(5):576-585.

[12]Kroemer, G., Levine, B., 2008. Autophagic cell death: the story of a misnomer. Nat. Rev. Mol. Cell Biol., 9(12):1004-1010.

[13]Malaguarnera, M., Cammalleri, L., Gargante, M.P., et al., 2007. L-Carnitine treatment reduces severity of physical and mental fatigue and increases cognitive functions in centenarians: a randomized and controlled clinical trial. Am. J. Clin. Nutr., 86(6):1738-1744.

[14]Matalliotakis, I., Koumantaki, Y., Evageliou, A., et al., 2000. L-Carnitine levels in the seminal plasma of fertile and infertile men: correlation with sperm quality. Int. J. Fertil. Womens Med., 45(3):236-240.

[15]Moradi, M., Moradi, A., Alemi, M., et al., 2010. Safety and efficacy of clomiphene citrate and L-carnitine in idiopathic male infertility: a comparative study. Urol. J., 7(3):188-193.

[16]Ohsumi, Y., 2001. Molecular dissection of autophagy: two ubiquitin-like systems. Nat. Rev. Mol. Cell. Biol., 2(3):211-216.

[17]Tanida, I., Ueno, T., Kominami, E., 2008. LC3 and autophagy. In: Deretic, V. (Ed.), Autophagosome and Phagosome. Methods in Molecular Biology™. Humana Press, Vol. 445, p.77-88.

[18]Tasi, Y.C., Chao, H.C., Chung, C.L., et al., 2013. Characterization of 3-hydroxyisobutyrate dehydrogenase, HIBADH, as a sperm-motility marker. J. Assist. Reprod. Genet., 30(4):505-512.

[19]Topcu-Tarladacalisir, Y., Kanter, M., Uzal, M.C., 2009. Role of L-carnitine in the prevention of seminiferous tubules damage induced by gamma radiation: a light and electron microscopic study. Arch. Toxicol., 83(8):735-746.

[20]Trasler, J.M., Robaire, B., 1988. Effects of cyclophosphamide on selected cytosolic and mitochondrial enzymes in the epididymis of the rat. J. Androl., 9(2):142-152.

[21]Tripathi, D.N., Jena, G.B., 2008. Astaxanthin inhibits cytotoxic and genotoxic effects of cyclophosphamide in mice germ cells. Toxicology, 248(2-3):96-103.

[22]Xie, H., Tang, S.Y., Li, H., et al., 2008. L-Carnitine protects against apoptosis of murine MC3T3-E1 osteoblastic cells. Amino Acids, 35(2):419-423.

[23]Ye, L.X., Yu, J., Liang, Y.X., et al., 2014. Beclin 1 knockdown retards re-endothelialization and exacerbates neointimal formation via a crosstalk between autophagy and apoptosis. Atherosclerosis, 237(1):146-154.

Open peer comments: Debate/Discuss/Question/Opinion


Please provide your name, email address and a comment

Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE