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N-Acetylcysteine May Regulate Altered Meteorin-Like Levels in Testicular Tissue due to Aluminum Exposure

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Abstract

Aluminum (AL) is a heavy metal known to have toxic effects on the reproductive system. It is known that N-acetylcysteine (NAC), which has an antioxidant effect, is a useful chelator for heavy metals. This study aimed to determine whether NAC may reduce AL-induced oxidative stress, inflammation, and germ cell apoptosis in testicular tissues and its effects on meteorin-like (METRNL) levels, which are known to play a role in energy metabolism. In this experimental study, 28 Sprague–Dawley male rats were randomly divided into 4 groups (n = 7): control, AL (30 mg/kg/day AL), AL + NAC (30 mg/kg/day AL + 150 mg/kg/day NAC), and NAC (150 mg/kg/day NAC). All AL and NAC applications were performed intraperitoneally for 14 days. At the end of the experiment, the effects of AL and/or NAC applications on testicular tissue were examined histomorphometrically, histopathologically, immunohistochemically, and biochemically. It was determined that AL exposure caused histomorphometric and histopathological changes, oxidative stress, apoptosis of germ cells, and inflammation in testicular tissues. In addition, AL caused an increase in METRNL levels. It was determined that NAC treatment significantly reduced the negative effects of AL. NAC therapy may be a protective strategy in reproductive toxicity due to AL exposure.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Akinola BK, Olawuyi TS, Ukwenya VO et al (2021) Protective effects of aloe vera gel (aloe baberdensis Miller) on aluminum chloride-induced reproductive toxicity in male Wistar rats. JBRA Assist Reprod 25(2):193–201. https://doi.org/10.5935/1518-0557.20200082

    Article  PubMed Central  PubMed  Google Scholar 

  2. Djouina M, Esquerre N, Desreumaux P et al (2016) Toxicological consequences of experimental exposure to aluminum in human intestinal epithelial cells. Food Chem Toxicol 91:108–116. https://doi.org/10.1016/j.fct.2016.03.008

    Article  CAS  PubMed  Google Scholar 

  3. Sun X, Sun H, Yu K et al (2018) Aluminum chloride causes the dysfunction of testes through inhibiting the ATPase enzyme activities and gonadotropin receptor expression in rats. Biol Trace Elem Res 183:296–304. https://doi.org/10.1007/s12011-017-1120-1

    Article  CAS  PubMed  Google Scholar 

  4. Cao C, Zhang H, Wang K et al (2020) Selenium-rich yeast mitigates aluminum-mediated testicular toxicity by blocking oxidative stress, inhibiting NO production, and disturbing ionic homeostasis. Biol Trace Elem Res 195:170–177. https://doi.org/10.1007/s12011-019-01820-5

    Article  CAS  PubMed  Google Scholar 

  5. Lokman M, Ashraf E, Kassab RB et al (2022) Aluminum chloride–induced reproductive toxicity in rats: the protective role of zinc oxide nanoparticles. Biol Trace Elem Res 200:4035–4044. https://doi.org/10.1007/s12011-021-03010-8

    Article  CAS  PubMed  Google Scholar 

  6. Jebur AB, El-Demerdash FM, Kang W (2020) Bromelain from Ananas comosus stem attenuates oxidative toxicity and testicular dysfunction caused by aluminum in rats. J Trace Elem Med Biol 62:126631. https://doi.org/10.1016/j.jtemb.2020.126631

    Article  CAS  PubMed  Google Scholar 

  7. Ahmed SA, Mohammed WI (2021) Carvedilol induces the antiapoptotic proteins Nrf2 and Bcl2 and inhibits cellular apoptosis in aluminum-induced testicular toxicity in male Wistar rats. Biomed Pharmacotherapy 139:111594. https://doi.org/10.1016/j.biopha.2021.111594

    Article  CAS  Google Scholar 

  8. Mohammad NS, Arafa MH, Atteia HH (2015) Coenzyme Q10 and fish oil synergistically alleviate aluminum chloride-induced suppression of testicular steroidogenesis and antioxidant defense. Free Radic Res 49(11):1319–1334. https://doi.org/10.3109/10715762.2015.1069290

    Article  CAS  PubMed  Google Scholar 

  9. Mohamed NE, Abd El-Moneim AE (2017) Ginkgo biloba extract alleviates oxidative stress and some neurotransmitters changes induced by aluminum chloride in rats. Nutrition 35:93–99. https://doi.org/10.1016/j.nut.2016.10.012

    Article  CAS  PubMed  Google Scholar 

  10. AbediniBajgiran F, KhazaeiKoohpar Z, Salehzadeh A (2022) Effects of N-acetylcysteine supplementation on oxidative stress and expression of apoptosis-related genes in testicular tissue of rats exposed to lead. Biol Trace Elem Res. https://doi.org/10.1007/s12011-022-03325-0

    Article  Google Scholar 

  11. Grinberg L, Fibach E, Amer J et al (2005) N-acetylcysteine amide, a novel cell-permeating thiol, restores cellular glutathione and protects human red blood cells from oxidative stress. Free Radic Biol Med 38(1):136–145. https://doi.org/10.1016/j.freeradbiomed.2004.09.025

    Article  CAS  PubMed  Google Scholar 

  12. Elnagar A, Ibrahim A, Soliman AM (2018) Histopathological effects of titanium dioxide nanoparticles and the possible protective role of N-acetylcysteine on the testes of male albino rats. Int J Fertil Steril 12(3):249–256. https://doi.org/10.22074/ijfs.2018.5389

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. El-Kirdasy AF, Nassan MA, Baiomy AAA et al (2014) Potential ameliorative role of n-acetylcysteine against testicular dysfunction induced by titanium dioxide in male albino rats. Am J Pharmacol Toxicol 9(1):29–38. https://doi.org/10.3844/ajptsp.2014.29.38

    Article  CAS  Google Scholar 

  14. Anand H, Misro MM, Sharma SB et al (2015) Protective effects of Eugenia jambolana extract versus N-acetyl cysteine against cisplatin-induced damage in rat testis. Andrologia 47(2):194–208. https://doi.org/10.1111/and.12247

    Article  CAS  PubMed  Google Scholar 

  15. Kaya S, Yalçın T, Boydak M et al (2022) Protective effect of N-acetylcysteine against aluminum-induced kidney tissue damage in rats. Biol Trace Elem Res. https://doi.org/10.1007/s12011-022-03276-6

    Article  PubMed  Google Scholar 

  16. Ji YL, Wang H, Zhang C et al (2013) N-acetylcysteine protects against cadmium-induced germ cell apoptosis by inhibiting endoplasmic reticulum stress in testes. Asian J Androl 15(2):290. https://doi.org/10.1038/aja.2012.129

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Rao RR, Long JZ, White JP et al (2014) Meteorin-like is a hormone that regulates immune-adipose interactions to increase beige fat thermogenesis. Cell 157:1279–1291. https://doi.org/10.1016/j.cell.2014.03.065

    Article  CAS  PubMed  Google Scholar 

  18. Baht GS, Bareja A, Lee DE et al (2020) Meteorin-like facilitates skeletal muscle repair through a Stat 3/IGF-1 mechanism. Nat Metab 2:278–289. https://doi.org/10.1038/s42255-020-0184-y

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Li ZY, Zheng SL, Wang P et al (2014) Subfatin is a novel adipokine and unlike Meteorin in adipose and brain expression. CNS Neurosci Ther 20:344–354

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Kaya S, Yalçın T, Kuloğlu T (2023) Resveratrol may reduce oxidative stress and apoptosis in doxorubicin-induced cardiotoxicity by regulating meteorin-like and TRPM2 levels. Comp Clin Pathol 1–12. https://doi.org/10.1007/s00580-023-03449-2

  21. Xu L, Cai Y, Wang Y et al (2020) Meteorin-like (METRNL) attenuates myocardial ischemia/reperfusion injury-induced cardiomyocytes apoptosis by alleviating endoplasmic reticulum stress via activation of AMPK-PAK2 signaling in H9C2 cells Medical Science Monitor. Int Med J Experimental Clin Res 26:e924564–e924571

    CAS  Google Scholar 

  22. Ruperez C, Ferrer-Curriu G, Cervera-Barea A et al (2021) Meteorin-like/meteorin-beta protects heart against cardiac dysfunction. J Exp Med 218:e20201206

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Johnsen SG (1970) Testicular biopsy score count–a method for registration of spermatogenesis in human testes: normal values and results in 335 hypogonadal males. Hormone Res Paediatrics 1(1):2–25. https://doi.org/10.1159/000178170

    Article  CAS  Google Scholar 

  24. Yalçın T, Kaya S (2023) Thymoquinone may alleviate cisplatin-induced muscle atrophy in rats by regulating mitofusin 2 and meteorin-like levels. Comp Clin Pathol 1–7. https://doi.org/10.1007/s00580-023-03442-9

  25. Karagüzel E, Kutlu Ö, Yuluğ E et al (2012) Comparison of the protective effect of dipyridamole and acetylsalicylic acid on long-term histologic damage in a rat model of testicular ischemia-reperfusion injury. J Pediatr Surg 47(9):1716–1723. https://doi.org/10.1016/j.jpedsurg.2012.01.078

    Article  PubMed  Google Scholar 

  26. Pandey G, Jain GC (2013) A review on toxic effects of aluminum exposure on male reproductive system and probable mechanisms of toxicity. Int J Toxicol Appl Pharmacol 3:48–57. https://doi.org/10.22074/ijfs.2017.4859

    Article  CAS  Google Scholar 

  27. Olanrewaju JA, Akinpade TG, Olatunji SY et al (2021) Observable protective activities of quercetin on aluminum chloride-induced testicular toxicity in adult male Wistar Rat. J Human Reprod Sci 14(2):113

    Article  CAS  Google Scholar 

  28. Mahmoud AA, Elfiky AM, Elreedy HA et al (2022) Quercetin attenuates testicular dysfunction induced by aluminum chloride in male Wistar rats. Egyp J Chem 65(6):1–2. https://doi.org/10.21608/EJCHEM.2021.102711.4760

    Article  Google Scholar 

  29. Falana B et al (2017) Effect of D-ribose-L-cysteine on aluminum induced testicular damage in male Sprague-Dawley rats. JBRA Assisted Reproduction 21(2):94–100. https://doi.org/10.5935/1518-0557.20170023

    Article  PubMed  Google Scholar 

  30. Boudou F, Bendahmane-Salmı M, Benabderrahmane M et al (2020) Effect of Curcuma longa aqueous extract on male fertility in aluminum exposed Wistar rats. J Drug Deliv Therapeutics 10(5):11–17

    Article  CAS  Google Scholar 

  31. OzcanYildirim S, Colakoglu N, Ozer Kaya S (2022) Protective effects of L-arginine against aluminium chloride-induced testicular damage in rats. Andrologia 54(11):14569. https://doi.org/10.1111/and.14569

    Article  CAS  Google Scholar 

  32. Cheraghi E, Golkar A, Roshanaei K et al (2017) Aluminium-induced oxidative stress, apoptosis and alterations in testicular tissue and sperm quality in Wistar rats: ameliorative effects of curcumin. Int J Fertil Steril 11(3):166

    CAS  PubMed Central  PubMed  Google Scholar 

  33. Liu Z, He C, Chen M et al (2018) The effects of lead and aluminum exposure on congenital heart disease and the mechanism of oxidative stress. Reprod Toxicol 81:93–98. https://doi.org/10.1016/j.reprotox.2018.07.081

    Article  CAS  PubMed  Google Scholar 

  34. Guo C, Hsu GW, Chuang C et al (2009) Aluminum accumulation induced testicular oxidative stress and altered selenium metabolism in mice. Environ Toxicol Pharmacol 27:176–181. https://doi.org/10.1016/j.etap.2008.10.001

    Article  CAS  PubMed  Google Scholar 

  35. Yeh CC, Hou MF, Tsai SM et al (2005) Superoxide anion radical, lipid peroxides and antioxidant status in the blood of patients with breast cancer. Clin Chem Acta 361:104–111. https://doi.org/10.1016/j.cccn.2005.05.002

    Article  CAS  Google Scholar 

  36. Turner TT, Lysiak JJ (2008) Oxidative stress: a common factor in testicular dysfunction. J Androl 29(5):488–498. https://doi.org/10.2164/jandrol.108.005132

    Article  CAS  PubMed  Google Scholar 

  37. Yan L, Yue D, Luo H et al (2010) Effect of vitamin E supplementation on the enzymatic activity of selected markers in Aohan fine-wool sheep testis. Anim Reprod Sci 122(3–4):264–269

    Article  CAS  PubMed  Google Scholar 

  38. Lv Y, Liu Z, Tian Y et al (2013) Effect on morphology, oxidative stress and energy metabolism enzymes in the testes of mice after a 13-week oral administration of melamine and cyanuric acid combination. Regul Toxicol Pharmacol 65(2):183–188

    Article  CAS  PubMed  Google Scholar 

  39. Klepac K, Georgiadi A, Tschöp M et al (2019) The role of brown and beige adipose tissue in glycaemic control. Mol Aspects Med 68:90–100. https://doi.org/10.1016/j.mam.2019.07.001

    Article  CAS  PubMed  Google Scholar 

  40. Anderson RM, Barger JL, Edwards MG et al (2008) Dynamic regulation of PGC-1α localization and turnover implicates mitochondrial adaptation in calorie restriction and the stress response. Aging Cell 7:101–111. https://doi.org/10.1111/j.1474-9726.2007.00357.x

    Article  CAS  PubMed  Google Scholar 

  41. Marmolino D, Manto M, Acquaviva F et al (2010) PGC-1alpha down-regulation affects the antioxidant response in Friedreich’s ataxia. PLoS One 5:10025. https://doi.org/10.1371/journal.pone.0010025

    Article  CAS  Google Scholar 

  42. Qiu X, Brown K, Hirschey MD et al (2010) Calorie restriction reduces oxidative stress by SIRT3-mediated SOD2 activation. Cell Metab 12:662–667. https://doi.org/10.1016/j.cmet.2010.11.015

    Article  CAS  PubMed  Google Scholar 

  43. Renu K, Gopalakrishnan AV (2019) Deciphering the molecular mechanism during doxorubicin-mediated oxidative stress, apoptosis through Nrf2 and PGC-1α in a rat testicular milieu. Reprod Biol 19(1):22–37

    Article  PubMed  Google Scholar 

  44. Kang C, Li Ji L (2012) Role of PGC-1α signaling in skeletal muscle health and disease. Ann N Y Acad Sci 1271(1):110–117. https://doi.org/10.1111/j.1749-6632.2012.06738.x

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Rius-Pérez S, Torres-Cuevas I, Millán I et al (2020) PGC-1α, inflammation, and oxidative stress: an integrative view in metabolism. Oxid Med Cell Longev. https://doi.org/10.1155/2020/1452696

    Article  PubMed  Google Scholar 

  46. Amano Y, Nonaka Y, Takeda R et al (2020) Effects of electrical stimulation-induced resistance exercise training on white and brown adipose tissues and plasma meteorin-like concentration in rats. Physiological Rep 8(16):14540. https://doi.org/10.14814/phy2.14540

    Article  CAS  Google Scholar 

  47. Sharma DR, Sunkaria A, Wani WY et al (2013) Aluminium induced oxidative stress results in decreased mitochondrial biogenesis via modulation of PGC-1α expression. Toxicol Appl Pharmacol 273(2):365–380. https://doi.org/10.1016/j.taap.2013.09.012

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Vocational Higher School of Healthcare Studies, Batman University, Batman, Turkey

    Tuba Yalçın & Sercan Kaya

  2. Department of Histology and Embryology, Faculty of Medicine, Firat University, Elazig, Turkey

    Tuncay Kuloğlu

  3. Department of Genetics, Faculty of Veterinary Medicine, Harran University, Sanliurfa, Turkey

    Akın Yiğin

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  1. Tuba Yalçın
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  2. Sercan Kaya
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T.Y. and S.K. data collection, analysis, interpretation and article writing. T.K. interpretation and critical analysis. A.Y. analysis and interpretation. All authors have reviewed and approved the final version of the article.

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Correspondence to Sercan Kaya.

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Yalçın, T., Kaya, S., Kuloğlu, T. et al. N-Acetylcysteine May Regulate Altered Meteorin-Like Levels in Testicular Tissue due to Aluminum Exposure. Biol Trace Elem Res 201, 5335–5345 (2023). https://doi.org/10.1007/s12011-023-03656-6

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