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http://dx.doi.org/10.15616/BSL.2019.25.4.417

The Protective Effects of N-Acetyl-L-cysteine on Cadmium-induced Cell Apoptosis in Rat Testis  

Kim, Ji-Sun (Medical University of South Carolina)
Soh, Jaemog (Hormone Research Center, Division of Biological Sciences and Technology, College of Natural Sciences, Chonnam National University)
Publication Information
Biomedical Science Letters / v.25, no.4, 2019 , pp. 417-425 More about this Journal
Abstract
Cadmium (Cd) generates reactive oxygen species (ROS), which in turn cause the apoptosis of various cell types including developing germ cells in rodent testis. Ascorbic acids (AA), one of the ROS scavengers, had been reported to protect against Cd-induced apoptosis. N-Acetyl-L-cysteine (NAC), another ROS scavenger, is known to remove ROS and alleviate the Cd-induced apoptosis in various cell types. In this study we tried to elucidate how NAC affected on Cd-induced cell apoptosis in rat testis. Rats were administered with NAC before and after Cd treatment and then testicular cell apoptosis was examined. NAC treatment resulted in the reduction of Cd-induced chromosomal DNA fragmentation in agarose gel electrophoresis. Terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) assay showed that treatment of NAC reduced the Cd-induced apoptosis of germ cells. The administration of NAC showed that the translocation of apoptosis inducing factor (AIF) from mitochondria to nucleus was prevented, which indicated that the mechanism of Cd-induced testicular apoptosis is mediated through the release of AIF in caspase-independent manner. Taken together, the NAC may remove Cd-induced ROS and protect ROS-induced cell apoptosis in rat testis.
Keywords
N-Acetyl-L-cysteine; Cadmium; Apoptosis; Testis; Rat;
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1 Ates B, Abraham L, Ercal, N. Antioxidant and free radical scavenging properties of N-acetylcysteine amide (NACA) and comparison with N-acetylcystein (NAC). Free Radic Res. 2008. 42: 372-377.   DOI
2 Cox B, Emili A. Tissue subcellular fractionation and protein extraction for use in mass-spectrometry-based proteomics. Nat Protoc. 2006. 1: 1872-1878.   DOI
3 Cregan SP, Dawson VL, Slack RS. Role of AIF in caspasedependent and caspase-independent cell death. Oncogene. 2004. 23: 2785-2796.   DOI
4 Dhandra S, Kaur S, Sandhir R. Preventive effect of N-acetyl-Lcystein on oxidative stress and cognitive impairment in hepatic encephalopathy following bile duct ligation. Free Radic Biol Med. 2013. 56: 204-215.   DOI
5 Gomes C, Oh SD, Kim JW, Chun SY, Lee K, Kwon HB, Soh J. Expression of the putative sterol binding protein Stard6 gene is male germ cell specific. Biol Reprod. 2005. 72: 651-658.   DOI
6 Gomes C, Soh J. DnaJC18, novel type III DnaJ family protein, is expressed specifically in rat male germ cells. Dev Reprod. 2017. 21: 237-247.   DOI
7 Jahnukainen K, Chrysis D, Hou M, Parvinen M, Eksborg S, Soder O. Increased apoptosis occurring during the first wave of spermatogenesis is stage-specific and primarily affects midpachytene spermatocytes in the rat testis. Biol Reprod. 2004. 70: 290-296.   DOI
8 Ji YL, Wang H, Zhao XF, Wang Q, Zhang C, Zhang Y, Zhao M, Chen YH, Meng XH, Xu DX. Crosstalk between endoplasmic reticulum stress and mitochondrial pathway mediates cadmiuminduced germ cell apoptosis in testes. Toxicol Sci. 2011. 124: 446-459.   DOI
9 Acharya UR, Mishra M, Patro J, Panda MK. Effect of vitamin C and E on spermatogenesis in mice exposed to cadmium. Reprod Toxicol. 2008. 25: 84-88.   DOI
10 Aldini G, Altomare A, Baron G, Vistoli G, Carini M, Borsani L, Sergio F. N-acetylcysteine as an antioxidant and disulphide breaking agent: the reason why. Free Radic Res. 2018. 52: 751-762.   DOI
11 Kaplan M, Atakan IH, Aydogdu N, Aktoz T, Ozpuyan F, Seren G, Tokuc, Inci O. Influence of N-acetylcysteine on renal toxicity of cadmium in rats. Pediatr Nephrol. 2008. 23: 233-241.   DOI
12 Khojastehfar A, Aghaei M, Gharagozloo M, Panjehpour M. Cadmium induces reactive oxygen species-dependent apoptosis in MCF-7 human breast cancer cell line. Toxicol Mech Methods. 2015. 25: 48-55.   DOI
13 Kim J, Soh J. Cadmium-induced apoptosis is mediated by the translocation of AIF to the nucleus in rat testes. Toxicol Letters. 2009. 188: 45-51.   DOI
14 Li M, Kondo T, Zhao QL. Li FJ, Tanabe K, Arai Y, Zhou ZC, Kasuya M. Apoptosis induced by cadmium in human lymphoma U937 cells through $Ca2^+$ caplain and caspase-mitochodriadependent pathway. J Biol Chem. 2000. 275: 39702-39709.   DOI
15 Kondoh M, Araragi S, Sato K, Higashimoto M, Takiguchi M, Sato M. Cadmium induces apoptosis partly via caspase-9 activation in HL-60 cells. Toxicology. 2002. 170: 111-117.   DOI
16 Krantic S, Mechawar N, Reix S, Quirion R. Apoptosis-inducing factor: a matter of neuron life and death. Prog Neurobiol. 2007. 81: 179-196.   DOI
17 Lemarie A, Lagadic-Gossmann D, Morzadec C, Allain N, Fardel O, Vernhet L. Cadmium induces caspase-independent apoptosis in liver Hep3B cells: role for calcium in signaling oxidative stress-related impairment of mitochondria and relocation of endonuclease G and apoptosis-inducing factor. Free Radic Biol Med. 2004. 36: 1517-1531.   DOI
18 Li R, Luo X, Li L, Peng Q, Yang Y, Zhao L, Ma M, Hou Z. The protective effects of melatonin against oxidative stress and inflammation induced by acute cadmium exposure in mice testis. Biol Trace Elem Res. 2016. 170: 152-164.   DOI
19 Li Y, Wu J, Zhou W, Gao E. Association between environmental exposure to cadmium and human semen quality. 2016. 26: 175-186.   DOI
20 Lemarie A, Lagadic-Gossmann D, Morzadec C, Allain N, Fardel O, Vernhet L. Cadmium induces caspase-independent apoptosis in liver Hep3B cells: role for calcium in signaling oxidative stress-related impairment of mitochondria and relocation of endonuclease G and apoptosis-inducing factor. Free Radic Biol Med. 2004. 36: 1517-1531.   DOI
21 Lopez E, Arce C, Oset-Gasque MJ, Canadas S, Gonzalez MP. Cadmium induces reactive oxygen species generation and lipid peroxidation in cortical neurons in culture. Free Radic Biol Med. 2006. 40: 940-951.   DOI
22 Sagrista ML, Garcia AE, Africa De Madariaga M, Mora M. Antioxidant and pro-oxidant effect of the thiolic compounds Nacetyl-L-cysteine and glutathione against free radical-induced lipid peroxidation. Free Radic Res. 2002. 36: 329-340.   DOI
23 Ognjanovic BI, Markovic SD, Pavlovic SZ, Zikic RV, Stajn AS, Saicic ZS. Effect of chronic cadmium exposure on antioxidant defense system in some tissues of rats: protective effect of selenium. Physiol Res. 2008. 57: 403-411.
24 Ortiz MS, Forti KM, Suarez Martinez EB, Munoz LG, Husain K, Muniz WH. Effects of antioxidant N-acetylcysteine against paraquat-induced oxidative stress in vital tissues of mice. Int J Sci Basic Appl Res. 2016. 26: 26-46.
25 Pant N, Kumar G, Upadhyay AD, Gupta YK, Chaturvedi PK. Correlation between lead and cadmium concentration and semen quality. Andrologia. 2015. 47: 887-891.   DOI
26 Siu PM, Bryner RW, Martyn JK, Alway SE. Apoptotic adaptations from exercise training in skeletal and cardiac muscles. FASEB J. 2004. 18: 1150-1152.   DOI
27 Sen Gupta R, Kim J, Gomes C, Oh S, Park J, Im WB, Seong JY, Ahn RS, Kwon HB, Soh J. Effect of ascorbic acid supplementation on testicular steroidogenesis and germ cell death in cadmium-treated male rats. Mol Cell Endocrinol. 2004. 30: 57-66.
28 Shih CM, Ko WC, Wu JS, Wei YH, Wang LF, Chang EE, Lo TY, Cheng HH, Chen CT. Mediating of caspase-independent apoptosis by cadmium through the mitochondria-ROS pathway in MRC-5 fibroblasts. J Cell Biochem. 2004. 91: 384-397.   DOI
29 Simon HU, Haj-Yehia A, Levi-Schaffer F. Role of reactive species (ROS) in apoptosis induction. Apotosis. 2000. 5: 415-418.   DOI
30 Xu C, Johnson JE, Singh PK, Jones MM, Yan H, Carter CE. In vivo studies of cadmium-induced apoptosis in testicular tissue of rat and its modulation by a chelating agent. Toxicology. 1996. 22: 1-8.   DOI
31 Zhao X, Cheng Z, Zhu YI, Li S, Zhang L, Luo Y. Effects of paternal cadmium exposure on the sperm quality of male rats and the neurobehavioral system of their offspring. Exp Ther Med. 2015. 10: 2356-2360.   DOI