Abstract
Cadmium (Cd) has been reported to reduce male fertility, impair reproductive capacity, and play a major role in the pathogenesis of infertility. This study was conducted to investigate the possible protective role of Selenium (Se) and L-carnitine (LC) against the adverse effects induced by Cd on the male reproductive system in mice. Animals were randomly divided into seven groups (n = 10); control group and six treated groups, as follows: Cd (0.35 mg/kg), Se (0.87 mg/kg), LC (10 mg/kg), and a combination of either Se or LC and then a combination of both with Cd, and all animals were injected for a period of 30 days. Exposure of Cd showed a significant decrease in enzymatic antioxidant activities, deficiency in reproductive performance, decrease serum testosterone level, severe changes in the histopathological architecture, and higher degree of damages and appearance of unblemished DNA strands. Treatment with Se and LC has the highly synergistic and ameliorates the damaging effect of Cd on the testis through the elevation of the enzymatic antioxidant and diminish histopathological abnormalities and DNA damage.
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Rani A, Kumar A, Lal A, Pant M (2014) Cellular mechanisms of cadmium-induced toxicity: a review. Int J Environ Health Res 24:378–399
L-n SUN et al (2006) Temporal-spatial distribution and variability of cadmium contamination in soils in Shenyang Zhangshi irrigation area, China. J Environ Sci 18:1241–1246
Janicka M, Binkowski ŁJ, Błaszczyk M, Paluch J, Wojtaś W, Massanyi P, Stawarz R (2015) Cadmium, lead and mercury concentrations and their influence on morphological parameters in blood donors from different age groups from southern Poland. J Trace Elem Med Biol 29:342–346
Miller GZ, Harris ZE (2015) Hazardous metals in vintage plastic toys measured by a handheld X-ray fluorescence spectrometer. J Environ Health 77:8–13
Satarug S, Baker JR, Urbenjapol S, Haswell-Elkins M, Reilly PE, Williams DJ, Moore MR (2003) A global perspective on cadmium pollution and toxicity in non-occupationally exposed population. Toxicol Lett 137:65–83
Anetor JI (2012) Rising environmental cadmium levels in developing countries: threat to genome stability and health. Nigerian journal of physiological sciences 27:103–115
Shimada H, Narumi R, Nagano M, Yasutake A, Waalkes MP, Imamura Y (2009) Strain difference of cadmium-induced testicular toxicity in inbred Wistar–Imamichi and Fischer 344 rats. Arch Toxicol 83:647–652
Cancer IAfRo: Beryllium, cadmium, mercury, and exposures in the glass. Apresentado em: IARC Working Group on the Evaluation of Carcinogenic Risks to Humans: Beryllium, Lyon, 1993. 1993
Arroyo V et al (2012) Liver and cadmium toxicity. J Drug Metab Toxicol 5:1–7
Ciarrocca M, Capozzella A, Tomei F, Tomei G, Caciari T (2013) Exposure to cadmium in male urban and rural workers and effects on FSH, LH and testosterone. Chemosphere 90:2077–2084
Fouad A, Jresat I (2015) Thymoquinone therapy abrogates toxic effect of cadmium on rat testes. Andrologia 47:417–426
Siu ER, Mruk DD, Porto CS, Cheng CY (2009) Cadmium-induced testicular injury. Toxicol Appl Pharmacol 238:240–249
Lafuente A (2013) The hypothalamic–pituitary–gonadal axis is target of cadmium toxicity. An update of recent studies and potential therapeutic approaches. Food Chem Toxicol 59:395–404
Jahan S, Khan M, Ahmed S, Ullah H (2014) Comparative analysis of antioxidants against cadmium induced reproductive toxicity in adult male rats. Syst Biol Reprod Med 60:28–34
Fang Y-Z, Yang S, Wu G (2002) free radicals, antioxidants, and nutrition. Nutrition 18:872–879
Rinaldi M, Micali A, Marini H, Adamo EB, Puzzolo D, Pisani A, Trichilo V, Altavilla D, Squadrito F, Minutoli L (2017) Cadmium, organ toxicity and therapeutic approaches: a review on brain, kidney and testis damage. Curr Med Chem 24:3879–3893
Nawrot TS, Staessen JA, Roels HA, Munters E, Cuypers A, Richart T, Ruttens A, Smeets K, Clijsters H, Vangronsveld J (2010) Cadmium exposure in the population: from health risks to strategies of prevention. Biometals 23:769–782
De Coster S, Van Larebeke N (2012) Endocrine-disrupting chemicals: associated disorders and mechanisms of action. J Environ Public Health:2012
Sharlip ID, Jarow JP, Belker AM, Lipshultz LI, Sigman M, Thomas AJ, Schlegel PN, Howards SS, Nehra A, Damewood MD, Overstreet JW, Sadovsky R (2002) Best practice policies for male infertility. Fertil Steril 77:873–882
Ahmed E, Nagaoka K, Fayez M, Samir H, Watanabe G (2015) Long-term p-nitrophenol exposure can disturb liver metabolic cytochrome P450 genes together with aryl hydrocarbon receptor in Japanese quail. Jpn J Vet Res 63:115–127
Chen J, Berry MJ (2003) Selenium and selenoproteins in the brain and brain diseases. J Neurochem 86:1–12
Wang N et al (2017) Supplementation of micronutrient selenium in metabolic diseases: its role as an antioxidant. Oxidative Med Cell Longev 2017
Li X et al (2017) Effects of selenium-lead interaction on the gene expression of inflammatory factors and selenoproteins in chicken neutrophils. Ecotoxicol Environ Saf 139:447–453
Jin X, Jia T, Liu R, Xu S (2018) The antagonistic effect of selenium on cadmium-induced apoptosis via PPAR-γ/PI3K/Akt pathway in chicken pancreas. J Hazard Mater 357:355–362
Abu-El-Zahab HS et al (2019) Antioxidant, antiapoptotic, antigenotoxic, and hepatic ameliorative effects of L-carnitine and selenium on cadmium-induced hepatotoxicity and alterations in liver cell structure in male mice. Ecotoxicol Environ Saf 173:419–428
Talib Ali AB (2009) G Bomboi, and B Floris: does vitamin E or vitamin E plus selenium improve reproductive performance of rams during hot weather? Ital J Anim Sci 8:743–754
Brown KM, Arthur J (2001) Selenium, selenoproteins and human health: a review. Public Health Nutr 4:593–599
Flanagan JL et al (2010) Role of carnitine in disease. Nutrition & metabolism 7:30
Gatti R, de Palo CB, Spinella P, de Palo EF (1998) Free carnitine and acetyl carnitine plasma levels and their relationship with body muscular mass in athletes. Amino Acids 14:361–369
Johri AM, Heyland DK, Hétu MF, Crawford B, Spence JD (2014) Carnitine therapy for the treatment of metabolic syndrome and cardiovascular disease: evidence and controversies. Nutr Metab Cardiovasc Dis 24:808–814
Gülçin İ (2006) Antioxidant and antiradical activities of L-carnitine. Life Sci 78:803–811
Kolodziejczyk J, Saluk-Juszczak J, Wachowicz B (2011) L-Carnitine protects plasma components against oxidative alterations. Nutrition 27:693–699
Sener G, Paskaloğlu K, Satiroglu H, Alican I, Kaçmaz A, Sakarcan A (2004) L-carnitine ameliorates oxidative damage due to chronic renal failure in rats. J Cardiovasc Pharmacol 43:698–705
Rani PJA, Panneerselvam C (2002) Effect of L-carnitine on brain lipid peroxidation and antioxidant enzymes in old rats. J Gerontol Ser A Biol Med Sci 57:B134–B137
Agarwal A And LH Sekhon: the role of antioxidant therapy in the treatment of male infertility. Hum Fertil 2010; 13: 217–225
Chen L, Liu L, Huang S (2008) cadmium activates the mitogen-activated protein kinase (MAPK) pathway via induction of reactive oxygen species and inhibition of protein phosphatases 2A and 5. Free Radic Biol Med 45:1035–1044
Bisht S et al (2017) Oxidative stress and male infertility. Nature Reviews Urology 14:470
Renugadevi J And SM Prabu: cadmium-induced hepatotoxicity in rats and the protective effect of naringenin. Exp Toxicol Pathol 2010; 62: 171–181
Johri S, Shukla S, Sharma P (2002) role of chelating agents and antioxidants in beryllium induced toxicity. Indian J Exp Biol 40:575–582
Elshazly SA et al (2012) Protective effect of L-carnitine against y-rays irradiation-induced tissue damage in mice. Am J Biochem Mol Biol 2:120–132
Aebi H (1984) Catalase in vitro in Methods in enzymology. Elsevier, pp 121–126
Beutler E (1963) Improved method for the determination of blood glutathione. J Lab Clin Med 61:882–888
Habig WH, Pabst MJ, Jakoby WB (1974) glutathione S-transferases the first enzymatic step in mercapturic acid formation. J Biol Chem 249:7130–7139
Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47:469–474
Wheeler M (1995) The determination of bio-available testosterone. Ann Clin Biochem 32:345–357
Drury RAB, Wallington EA, Cameron SR (1967) Carleton's histological technique, London
Endoh D et al (2002) Protective effect of a lignan-containing flaxseed extract against CCl4-induced hepatic injury. J Vet Med Sci 64:761–765
Collins AR, Dušinská M (2002) Oxidation of cellular DNA measured with the comet assay in Oxidative stress biomarkers and antioxidant protocols. Springer, pp 147–159
Liu X, Yao J, Pisha E, Yang Y, Hua Y, van Breemen R, Bolton JL (2002) Oxidative DNA damage induced by equine estrogen metabolites: role of estrogen receptor α. Chem Res Toxicol 15:512–519
El-Demerdash FM et al (2004) Cadmium-induced changes in lipid peroxidation, blood hematology, biochemical parameters and semen quality of male rats: protective role of vitamin E and β-carotene. Food Chem Toxicol 42:1563–1571
Adewoyin M et al (2017) Male infertility: the effect of natural antioxidants and phytocompounds on seminal oxidative stress. Diseases 5:9
Donpunha W, Kukongviriyapan U, Sompamit K, Pakdeechote P, Kukongviriyapan V, Pannangpetch P (2011) Protective effect of ascorbic acid on cadmium-induced hypertension and vascular dysfunction in mice. Biometals 24:105–115
Babaknejad N, Bahrami S, Moshtaghie AA, Nayeri H, Rajabi P, Iranpour FG (2018) Cadmium testicular toxicity in male Wistar rats: protective roles of zinc and magnesium. Biol Trace Elem Res 185:106–115
Surai P (2015) Silymarin as a natural antioxidant: an overview of the current evidence and perspectives. Antioxidants 4:204–247
Stanic B, Andric N, Zoric S, Grubor-Lajsic G, Kovacevic R (2006) Assessing pollution in the Danube River near Novi Sad (Serbia) using several biomarkers in sterlet (Acipenser ruthenus L.). Ecotoxicol Environ Saf 65:395–402
Regoli F et al (2003) Integrating enzymatic responses to organic chemical exposure with total oxyradical absorbing capacity and DNA damage in the European eel Anguilla anguilla. Environ Toxicol Chem 22:2120–2129
Kono K, Salazar-Onfray F, Petersson M, Hansson J, Masucci G, Wasserman K, Nakazawa T, Anderson P, Kiessling R (1996) Hydrogen peroxide secreted by tumor-derived macrophages down-modulates signal-transducing zeta molecules and inhibits tumor-specific T cell-and natural killer cell-mediated cytotoxicity. Eur J Immunol 26:1308–1313
Jensen TK et al (2006) Fertility treatment and reproductive health of male offspring: a study of 1,925 young men from the general population. Am J Epidemiol 165:583–590
Ten J et al (2008) Occupational and lifestyle exposures on male infertility: a mini review. The Open Reproductive Science Journal 1:16–21
Mathur N, Pandey G, Jain G (2010) male reproductive toxicity of some selected metals: a review. J Biol Sci 10:396–404
Erkekoglu P, Rachidi W, Yuzugullu OG, Giray B, Favier A, Ozturk M, Hincal F (2010) Evaluation of cytotoxicity and oxidative DNA damaging effects of di (2-ethylhexyl)-phthalate (DEHP) and mono (2-ethylhexyl)-phthalate (MEHP) on MA-10 Leydig cells and protection by selenium. Toxicol Appl Pharmacol 248:52–62
Ursini F, Heim S, Kiess M, Maiorino M, Roveri A, Wissing J, Flohé L (1999) Dual function of the selenoprotein PHGPx during sperm maturation. Science 285:1393–1396
Vanella A, Russo A, Acquaviva R, Campisi A, di Giacomo C, Sorrenti V, Barcellona ML (2000) L-propionyl-carnitine as superoxide scavenger, antioxidant, and DNA cleavage protector. Cell Biol Toxicol 16:99–104
Ramadan LA, Abd-Allah AR, Aly HA, Saad-el-Din AA (2002) Testicular toxicity effects of magnetic field exposure and prophylactic role of coenzyme Q10 and L-carnitine in mice. Pharmacol Res 46:363–370
Chang B et al (2002) L-Carnitine inhibits cisplatin-induced injury of the kidney and small intestine. Arch Biochem Biophys 405:55–64
Garcia CL et al (2005) The protective effect of L-carnitine in peripheral blood human lymphocytes exposed to oxidative agents. Mutagenesis 21:21–27
Jiang L, Cao J, An Y, Geng C, Qu S, Jiang L, Zhong L (2007) Genotoxicity of acrylamide in human hepatoma G2 (HepG2) cells. Toxicol in Vitro 21:1486–1492
Kocer I, Taysi S, Ertekin MV, Karslioglu I, Gepdiremen A, Sezen O, Serifoglu K (2007) The effect of L-carnitine in the prevention of ionizing radiation-induced cataracts: a rat model. Graefes Arch Clin Exp Ophthalmol 245:588–594
Berni A, Meschini R, Filippi S, Palitti F, de Amicis A, Chessa L (2008) L-carnitine enhances resistance to oxidative stress by reducing DNA damage in Ataxia telangiectasia cells. Mutation Research/Genetic Toxicology and Environmental Mutagenesis 650:165–174
Alzahrani HAS (2011) Protective effect of l-carnitine against acrylamide-induced DNA damage in somatic and germ cells of mice. Saudi journal of biological sciences 18:29–36
Tice R, Strauss G (1995) The single cell gel electrophoresis/comet assay: a potential tool for detecting radiation-induced DNA damage in humans. Stem Cells (Dayton, Ohio) 13:207–214
Collins AR et al (1996) Oxidative damage to DNA: do we have a reliable biomarker? Environ Health Perspect 104:465–469
dos Santos RA et al (2007) Protection of doxorubicin-induced DNA damage by sodium selenite and selenomethionine in Wistar rats. Nutr Res 27:343–348
Tapiero H, Townsend D, Tew K (2003) the antioxidant role of selenium and seleno-compounds. Biomed Pharmacother 57:134–144
Dalton TP, Shertzer HG, Puga A (1999) regulation of gene expression by reactive oxygen. Annu Rev Pharmacol Toxicol 39:67–101
e Luz EWM et al (2013) Neurobehavioral effects of L-carnitine and its ability to modulate genotoxicity and oxidative stress biomarkers in mice. Pharmacol Biochem Behav 110:40–45
Thangasamy T et al (2009) L-carnitine mediates protection against DNA damage in lymphocytes of aged rats. Biogerontology 10:163–172
Boerrigter ME, Franceschi C, Arrigoni-Martelli E, Wei JY, Vijg J (1993) The effect of L-carnitine and acetyl-L-carnitine on the disappearance of DNA single-strand breaks in human peripheral blood lymphocytes. Carcinogenesis 14:2131–2136
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Alharthi, W.A., Hamza, R.Z., Elmahdi, M.M. et al. Selenium and L-Carnitine Ameliorate Reproductive Toxicity Induced by Cadmium in Male Mice. Biol Trace Elem Res 197, 619–627 (2020). https://doi.org/10.1007/s12011-019-02016-7
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DOI: https://doi.org/10.1007/s12011-019-02016-7