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Apocynin Ameliorates Testicular Toxicity in High-Fat Diet-Fed Rats By Regulating Oxidative Stress

Year 2023, Volume: 13 Issue: 1, 75 - 83, 28.03.2023
https://doi.org/10.33808/clinexphealthsci.1035133

Abstract

Objective: The purpose of this study was to examine the effects of apocynin (APC), an inhibitor of NADPH oxidase (NOX), on high-fat diet (HF)-induced testis cytotoxicity.
Methods: Wistar albino rats were divided into three groups as control, HF and HF+APC groups. Rats in HF and HF+APC groups were fed using HF for 16 weeks and in the last four weeks of this period vehicle solution or APC (25 mg/kg) was administered orally five days a week, respectively. Control group was fed with standart lab chow for 16 weeks. Cholesterol, triglyceride, high-density lipoproteins, leptin, estrogen, testosterone, LH and FSH were estimated in blood serum. Sperm parameters were analysed from the epididymis. Testicular malondialdehyde, 8‐hydroxy‐2‐deoxyguanosine, glutathione, superoxide dismutase and myeloperoxidase levels were estimated biochemically. Testicular morphology, proliferative, apoptotic and NOX2-positive cells were analysed histologically. HF-induced obesity caused significant alterations in serum lipid and hormone profiles. Testicular malondialdehyde, 8‐hydroxy‐2‐deoxyguanosine, and myeloperoxidase levels increased, glutathione and superoxide dismutase levels decreased in this group. Moreover, altered sperm parameters, increased degenerated seminiferous tubules, apoptotic and NOX2- positive cells and decreased proliferative cells were observed in the HF group. All these biochemical and histological alterations improved in the HF+APC group.
Conclusion: HF-induced obesity causes altreations in lipid values, sperm parameters and testicular morphology by increasing oxidative stress through NOX2 activity. Apocynin might prevent testis damage via regulating oxidant/antioxidant balance.

Supporting Institution

Marmara University Scientific Research Project Committee

Project Number

YLP-131217-0655

Thanks

The authors would like to thank Dr. Dilek Akakın for comments of our manuscript

References

  • Manna P, Jain SK: Obesity, oxidative stress, adipose tissue dysfunction, and the associated health risks: Causes and therapeutic strategies. Metab Syndr Relat Disord 2015;13(10): 423-44.
  • Jung RT: Obesity as a disease. Br Med Bull 1997; 3 (2):307-321.
  • Hammoud AO, Meikle AW, Reis LO, Gibson M, Peterson CM, Carrell DT: Obesity and male infertility: a practical approach. Semin Reprod Med 2012;30(6):486-495.
  • Savini I, Catani MV, Evangelista D, Gasperi V, Aviglian L: Obesity-associated oxidative stress: Strategies finalized to improve redox state. Int J Mol Sci 2013;14:10497-10538.
  • Shokoohi M, Shoorei H, Soltani M, Abtahi-Eivari SH, Salimnejad R, Moghimian M: Protective effects of the hydroalcoholic extract of Fumaria parviflora on testicular injury induced by torsion/detorsion in adult rats. Andrologia 2018;50 (7): e13047.
  • Ribas-Maynou JR, Yeste M: Oxidative stress in male infertility: Causes, effects in assisted reproductive techniques, and protective support of antioxidants. Biology 2020; 9(4):77.
  • Mortazavi M, Salehi I, Alizadeh Z, Vahabian M, Roushandeh AM: Protective effects of antioxidants on sperm parameters and seminiferous tubules epithelium in high fat-fed rats. J Reprod Infertil 2014;15 (1):22-28.
  • Suleiman JB, Nna VU, Zakaria Z, Othman ZA, Bakar ABA, Mohamed M: Obesity-induced testicular oxidative stress, inflammation and apoptosis: Protective and therapeutic effects of orlistat. Reprod Toxicol 2020;95:113-122.
  • Filho DW, Torres MA, Bordin AL: Spermatic cord torsion, reactive oxygen and nitrogen species and ischemia–reperfusion injury. Mol Aspects Med 2004;25:199–210.
  • Stefanska J, Pawliczak R: Apocynin: Molecular aptitudes. Mediators Inflamm 2008;106507.
  • Connell BJ, Saleh MC, Khan BV, Saleh TM: Apocynin may limit total cell death following cerebral ischemia and reperfusion by enhancing apoptosis. Food Chem Toxicol 2011;49:3063–3069.
  • Köroğlu KM, Çevik Ö, Şener G, Ercan F: Apocynin alleviates cisplatin-induced testicular cytotoxicity by regulating oxidative stress and apoptosis in rats. Andrologia 2019;51(4): e13227.
  • Kavram SK, Yardimoğlu YM, Eraldemir FC, Yazir Y: Protective effects of apocynin on damaged testes of rats exposed to methotrexate. Turk J Med Sci, 50(5):20201409-1420.
  • Li M, Lıu Z, Zhuan L, Wang T, Guo S, Wang S, Lıu J, Ye Z: Effects of apocynin on oxidative stress and expression of apoptosis-related genes in testes of diabetic rats. Mol Med Rep 2013:7: 47-52.
  • Sener TE, Yüksel M, Özyılmaz-Yay N, Ercan F, Akbal C, Şimşek F, Şener G: Apocynin attenuates testicular ischemia–reperfusion injury in rats. J Pediatr Surg 2015:50:1382-1387.
  • Ozbek O, Altintas R, Polat A, Vardi N, Parlakpinar H, Sagir M, Duran ZR, Yildiz A: The protective effect of apocynin on testicular ischemia-reperfusion injury. J Urol 2015:193(4):1417-1422.
  • Arabacı Tamer S, Yıldırım A, Arabacı Ş, Çiftçi S, Akın S, Sarı E, Köroğlu MK, Ercan F, Yüksel M, Çevik Ö, Yeğen BÇ: Treatment with estrogen receptor agonist ERβ improves torsion-induced oxidative testis injury in rats. Life Sci 2019:222: 203-211.
  • Johnsen SG: Testicular biopsy score count: a method for registration of spermatogenesis in human testes. Normal values and results of 335 hypogonadal males. Hormones 1970:1, 2–25.
  • Sallmen M, Sandler DP, Hoppin JA, Blair A, Baird DD: Reduced fertility among overweight and obese men. Epidemiology 2006:17(5), 520-523.
  • Magnusdottir EV, Thorsteinsson T, Thorsteinsdottir S, Heimisdottir M, Olafsdottir K: Persistent organochlorines, sedentary occupation, obesity and human male subfertility. Human Reprod 2005:20(1), 208-215.
  • Miao XL, Gao GM, Jiang L, Xu R, Wan DP: Asiatic acid attenuates high-fat diet-induced impaired spermatogenesis. Exp Ther Med 2018:15(3), 2397-2403
  • Alshahrani S, Ahmed AF, Gabr AH, Abalhassan M, Ahmad G: The impact of body mass index on semen parameters in infertile men. Andrologia 2016:48(10), 1125-1129.
  • Martini AC, Tissera A, Estofán D, Molina RI, Mangeaud A, Cuneo MF, Ruiz RD: Overweight and seminal quality: a study of 794 patients. Fertil Steril 2010:94(5),1739-743.
  • Acıkel Elmas M, Arbak S, Ercan F: Ameliorating effects of exercise on disrupted epididymal sperm parameters in high fat diet-induced obese rats. Marmara Med J 2019:32, 14-19.
  • Jia YF, Feng Q, Ge ZY, Guo Y, Zhou F, Zhang KS, Wang XW, Lu WH, Liang XW, Gu YQ: Obesity impairs male fertility through long-term effects on spermatogenesis. BMC Urol 2018:18(1), 42.
  • Silva JF, Correa IC, Diniz TF, Lima PM, Santos RL, Cortes SF, Coimbra CC, Lemos VS: Obesity, inflammation, and exercise training: Relative contribution of iNOS and eNOS in the modulation of vascular function in the mouse aorta. Front Physiol 2016:7, 386.
  • Acikel Elmas M, Cakıcı SE, Dur IR, Kozluca I, Arınc M, Binbuga B, Bingol Ozakpınar O, Kolgazi M, Sener G, Ercan F: Protective effects of exercise on heart and aorta in high-fat diet-induced obese rats. Tissue Cell 2019:57, 57-65.
  • Farooq R, Lutfullah S, Ahmed M: Serum leptin levels in obese infertile men and women. Pak J Pharm Sci 2014:27(1): 67–71.
  • Ghanayem BI, Bai R, Kissling GE, Travlos G, Hoffler U: Diet-induced obesity in male mice is associated with reduced fertility and potentiation of acrylamide-induced reproductive toxicity. Biol Reprod 2010:82(1), 96-104.
  • Isidori AM, Caprio M, Strollo F: Leptin and androgens in male obesity: Evidence for leptin contribution to reduced androgen levels. J Clin Endocrinol Metab 1999:84: 3673–3680.
  • Yi X, Gao H, Chen D, Tang D, Huang W, Li T, Ma T, Chang B: Effects of obesity and exercise on testicular leptin signal transduction and testosterone biosynthesis in male mice. Am J Physiol Regul Integr Comp Physiol 2017:312(4), R501-R510.
  • Mintziori G, Nigdelis MP, Mathew H, Mousiolis A, Goulis DG, Mantzoros CS: The effect of excess body fat on female and male reproduction. Metabolism 2020:107:154193.
  • Leisegang K, Sengupta P, Agarwal A, Henkel R: Obesity and male infertility: Mechanisms and management. Andrologia 2021:53(1): e13617.
  • Blokhina O, Virolainen E, Fagerstedt KV: Antioxidants, oxidative damage and oxygen deprivation stress: a review. Ann Bot 2003:91: 179-194.
  • Vincent HK, Taylor AG: Biomarkers and potential mechanisms of obesity-induced oxidant stress in humans. Int J Obes (Lond) 2006:30(3): 400–418.
  • Ye J, Luo D, Xu X, Sun M, Su X, Tian Z, Zhang M, Yu C, Guan Q: Metformin improves fertility in obese males by alleviating oxidative stress-induced blood-testis barrier damage. Oxid Med Cell Longev, 2019:10: 9151067.
  • Aslankoc R, Ozmen O: The effects of high‐fructose corn syrup consumption on testis physiopathology The ameliorative role of melatonin. Andrologia 2019;51(8), e13327.
  • Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y, Nakayama O, Makishima M, Matsuda M, Shimomura I: Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 2004:114(12), 1752-1761.
  • Lapperre TS, Jimenez LA, Antonicelli F: Apocynin increases glutathione 421 synthesis and activates AP-1 in alveolar epithelial cells. FEBS Lett 1999:443: 235-239.
  • Meng R, Zhu D, Bi Y, Yang D, Wang Y: Anti-oxidative effect of apocynin on insulin resistance in high-fat diet mice. Ann Clin Lab Sci 2011; 41(3): 236-243.
  • Herishanu Y, Rogowski O, Polliack A, Marilus R: Leukocytosis in obese individuals: possible link in patients with unexplained persistent neutrophilia. Eur J Haematol 2006:76, 516–520.
  • Wiersma JJ, Meuwese MC, van Miert JN: Diabetes mellitus type 2 is associated with higher levels of myeloperoxidase. Med Sci Monit 2008:4(8): CR406–CR410
  • 43. Ghosh S, Mukherjee S: Testicular germ cell apoptosis and sperm defects in mice upon long‐term high fat diet feding. J Cell Physiol 2018;233 (10), 6896–6909.
Year 2023, Volume: 13 Issue: 1, 75 - 83, 28.03.2023
https://doi.org/10.33808/clinexphealthsci.1035133

Abstract

Project Number

YLP-131217-0655

References

  • Manna P, Jain SK: Obesity, oxidative stress, adipose tissue dysfunction, and the associated health risks: Causes and therapeutic strategies. Metab Syndr Relat Disord 2015;13(10): 423-44.
  • Jung RT: Obesity as a disease. Br Med Bull 1997; 3 (2):307-321.
  • Hammoud AO, Meikle AW, Reis LO, Gibson M, Peterson CM, Carrell DT: Obesity and male infertility: a practical approach. Semin Reprod Med 2012;30(6):486-495.
  • Savini I, Catani MV, Evangelista D, Gasperi V, Aviglian L: Obesity-associated oxidative stress: Strategies finalized to improve redox state. Int J Mol Sci 2013;14:10497-10538.
  • Shokoohi M, Shoorei H, Soltani M, Abtahi-Eivari SH, Salimnejad R, Moghimian M: Protective effects of the hydroalcoholic extract of Fumaria parviflora on testicular injury induced by torsion/detorsion in adult rats. Andrologia 2018;50 (7): e13047.
  • Ribas-Maynou JR, Yeste M: Oxidative stress in male infertility: Causes, effects in assisted reproductive techniques, and protective support of antioxidants. Biology 2020; 9(4):77.
  • Mortazavi M, Salehi I, Alizadeh Z, Vahabian M, Roushandeh AM: Protective effects of antioxidants on sperm parameters and seminiferous tubules epithelium in high fat-fed rats. J Reprod Infertil 2014;15 (1):22-28.
  • Suleiman JB, Nna VU, Zakaria Z, Othman ZA, Bakar ABA, Mohamed M: Obesity-induced testicular oxidative stress, inflammation and apoptosis: Protective and therapeutic effects of orlistat. Reprod Toxicol 2020;95:113-122.
  • Filho DW, Torres MA, Bordin AL: Spermatic cord torsion, reactive oxygen and nitrogen species and ischemia–reperfusion injury. Mol Aspects Med 2004;25:199–210.
  • Stefanska J, Pawliczak R: Apocynin: Molecular aptitudes. Mediators Inflamm 2008;106507.
  • Connell BJ, Saleh MC, Khan BV, Saleh TM: Apocynin may limit total cell death following cerebral ischemia and reperfusion by enhancing apoptosis. Food Chem Toxicol 2011;49:3063–3069.
  • Köroğlu KM, Çevik Ö, Şener G, Ercan F: Apocynin alleviates cisplatin-induced testicular cytotoxicity by regulating oxidative stress and apoptosis in rats. Andrologia 2019;51(4): e13227.
  • Kavram SK, Yardimoğlu YM, Eraldemir FC, Yazir Y: Protective effects of apocynin on damaged testes of rats exposed to methotrexate. Turk J Med Sci, 50(5):20201409-1420.
  • Li M, Lıu Z, Zhuan L, Wang T, Guo S, Wang S, Lıu J, Ye Z: Effects of apocynin on oxidative stress and expression of apoptosis-related genes in testes of diabetic rats. Mol Med Rep 2013:7: 47-52.
  • Sener TE, Yüksel M, Özyılmaz-Yay N, Ercan F, Akbal C, Şimşek F, Şener G: Apocynin attenuates testicular ischemia–reperfusion injury in rats. J Pediatr Surg 2015:50:1382-1387.
  • Ozbek O, Altintas R, Polat A, Vardi N, Parlakpinar H, Sagir M, Duran ZR, Yildiz A: The protective effect of apocynin on testicular ischemia-reperfusion injury. J Urol 2015:193(4):1417-1422.
  • Arabacı Tamer S, Yıldırım A, Arabacı Ş, Çiftçi S, Akın S, Sarı E, Köroğlu MK, Ercan F, Yüksel M, Çevik Ö, Yeğen BÇ: Treatment with estrogen receptor agonist ERβ improves torsion-induced oxidative testis injury in rats. Life Sci 2019:222: 203-211.
  • Johnsen SG: Testicular biopsy score count: a method for registration of spermatogenesis in human testes. Normal values and results of 335 hypogonadal males. Hormones 1970:1, 2–25.
  • Sallmen M, Sandler DP, Hoppin JA, Blair A, Baird DD: Reduced fertility among overweight and obese men. Epidemiology 2006:17(5), 520-523.
  • Magnusdottir EV, Thorsteinsson T, Thorsteinsdottir S, Heimisdottir M, Olafsdottir K: Persistent organochlorines, sedentary occupation, obesity and human male subfertility. Human Reprod 2005:20(1), 208-215.
  • Miao XL, Gao GM, Jiang L, Xu R, Wan DP: Asiatic acid attenuates high-fat diet-induced impaired spermatogenesis. Exp Ther Med 2018:15(3), 2397-2403
  • Alshahrani S, Ahmed AF, Gabr AH, Abalhassan M, Ahmad G: The impact of body mass index on semen parameters in infertile men. Andrologia 2016:48(10), 1125-1129.
  • Martini AC, Tissera A, Estofán D, Molina RI, Mangeaud A, Cuneo MF, Ruiz RD: Overweight and seminal quality: a study of 794 patients. Fertil Steril 2010:94(5),1739-743.
  • Acıkel Elmas M, Arbak S, Ercan F: Ameliorating effects of exercise on disrupted epididymal sperm parameters in high fat diet-induced obese rats. Marmara Med J 2019:32, 14-19.
  • Jia YF, Feng Q, Ge ZY, Guo Y, Zhou F, Zhang KS, Wang XW, Lu WH, Liang XW, Gu YQ: Obesity impairs male fertility through long-term effects on spermatogenesis. BMC Urol 2018:18(1), 42.
  • Silva JF, Correa IC, Diniz TF, Lima PM, Santos RL, Cortes SF, Coimbra CC, Lemos VS: Obesity, inflammation, and exercise training: Relative contribution of iNOS and eNOS in the modulation of vascular function in the mouse aorta. Front Physiol 2016:7, 386.
  • Acikel Elmas M, Cakıcı SE, Dur IR, Kozluca I, Arınc M, Binbuga B, Bingol Ozakpınar O, Kolgazi M, Sener G, Ercan F: Protective effects of exercise on heart and aorta in high-fat diet-induced obese rats. Tissue Cell 2019:57, 57-65.
  • Farooq R, Lutfullah S, Ahmed M: Serum leptin levels in obese infertile men and women. Pak J Pharm Sci 2014:27(1): 67–71.
  • Ghanayem BI, Bai R, Kissling GE, Travlos G, Hoffler U: Diet-induced obesity in male mice is associated with reduced fertility and potentiation of acrylamide-induced reproductive toxicity. Biol Reprod 2010:82(1), 96-104.
  • Isidori AM, Caprio M, Strollo F: Leptin and androgens in male obesity: Evidence for leptin contribution to reduced androgen levels. J Clin Endocrinol Metab 1999:84: 3673–3680.
  • Yi X, Gao H, Chen D, Tang D, Huang W, Li T, Ma T, Chang B: Effects of obesity and exercise on testicular leptin signal transduction and testosterone biosynthesis in male mice. Am J Physiol Regul Integr Comp Physiol 2017:312(4), R501-R510.
  • Mintziori G, Nigdelis MP, Mathew H, Mousiolis A, Goulis DG, Mantzoros CS: The effect of excess body fat on female and male reproduction. Metabolism 2020:107:154193.
  • Leisegang K, Sengupta P, Agarwal A, Henkel R: Obesity and male infertility: Mechanisms and management. Andrologia 2021:53(1): e13617.
  • Blokhina O, Virolainen E, Fagerstedt KV: Antioxidants, oxidative damage and oxygen deprivation stress: a review. Ann Bot 2003:91: 179-194.
  • Vincent HK, Taylor AG: Biomarkers and potential mechanisms of obesity-induced oxidant stress in humans. Int J Obes (Lond) 2006:30(3): 400–418.
  • Ye J, Luo D, Xu X, Sun M, Su X, Tian Z, Zhang M, Yu C, Guan Q: Metformin improves fertility in obese males by alleviating oxidative stress-induced blood-testis barrier damage. Oxid Med Cell Longev, 2019:10: 9151067.
  • Aslankoc R, Ozmen O: The effects of high‐fructose corn syrup consumption on testis physiopathology The ameliorative role of melatonin. Andrologia 2019;51(8), e13327.
  • Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y, Nakayama O, Makishima M, Matsuda M, Shimomura I: Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 2004:114(12), 1752-1761.
  • Lapperre TS, Jimenez LA, Antonicelli F: Apocynin increases glutathione 421 synthesis and activates AP-1 in alveolar epithelial cells. FEBS Lett 1999:443: 235-239.
  • Meng R, Zhu D, Bi Y, Yang D, Wang Y: Anti-oxidative effect of apocynin on insulin resistance in high-fat diet mice. Ann Clin Lab Sci 2011; 41(3): 236-243.
  • Herishanu Y, Rogowski O, Polliack A, Marilus R: Leukocytosis in obese individuals: possible link in patients with unexplained persistent neutrophilia. Eur J Haematol 2006:76, 516–520.
  • Wiersma JJ, Meuwese MC, van Miert JN: Diabetes mellitus type 2 is associated with higher levels of myeloperoxidase. Med Sci Monit 2008:4(8): CR406–CR410
  • 43. Ghosh S, Mukherjee S: Testicular germ cell apoptosis and sperm defects in mice upon long‐term high fat diet feding. J Cell Physiol 2018;233 (10), 6896–6909.
There are 43 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Articles
Authors

İrem Hersek This is me 0000-0003-4135-3614

M. Kutay Köroğlu This is me 0000-0002-5384-4472

Busra Coskunlu This is me 0000-0002-7410-7674

Büşra Ertaş 0000-0001-8374-1098

Göksel Şener 0000-0001-7444-6193

Feriha Ercan 0000-0003-2339-5669

Project Number YLP-131217-0655
Publication Date March 28, 2023
Submission Date December 10, 2021
Published in Issue Year 2023 Volume: 13 Issue: 1

Cite

APA Hersek, İ., Köroğlu, M. K., Coskunlu, B., Ertaş, B., et al. (2023). Apocynin Ameliorates Testicular Toxicity in High-Fat Diet-Fed Rats By Regulating Oxidative Stress. Clinical and Experimental Health Sciences, 13(1), 75-83. https://doi.org/10.33808/clinexphealthsci.1035133
AMA Hersek İ, Köroğlu MK, Coskunlu B, Ertaş B, Şener G, Ercan F. Apocynin Ameliorates Testicular Toxicity in High-Fat Diet-Fed Rats By Regulating Oxidative Stress. Clinical and Experimental Health Sciences. March 2023;13(1):75-83. doi:10.33808/clinexphealthsci.1035133
Chicago Hersek, İrem, M. Kutay Köroğlu, Busra Coskunlu, Büşra Ertaş, Göksel Şener, and Feriha Ercan. “Apocynin Ameliorates Testicular Toxicity in High-Fat Diet-Fed Rats By Regulating Oxidative Stress”. Clinical and Experimental Health Sciences 13, no. 1 (March 2023): 75-83. https://doi.org/10.33808/clinexphealthsci.1035133.
EndNote Hersek İ, Köroğlu MK, Coskunlu B, Ertaş B, Şener G, Ercan F (March 1, 2023) Apocynin Ameliorates Testicular Toxicity in High-Fat Diet-Fed Rats By Regulating Oxidative Stress. Clinical and Experimental Health Sciences 13 1 75–83.
IEEE İ. Hersek, M. K. Köroğlu, B. Coskunlu, B. Ertaş, G. Şener, and F. Ercan, “Apocynin Ameliorates Testicular Toxicity in High-Fat Diet-Fed Rats By Regulating Oxidative Stress”, Clinical and Experimental Health Sciences, vol. 13, no. 1, pp. 75–83, 2023, doi: 10.33808/clinexphealthsci.1035133.
ISNAD Hersek, İrem et al. “Apocynin Ameliorates Testicular Toxicity in High-Fat Diet-Fed Rats By Regulating Oxidative Stress”. Clinical and Experimental Health Sciences 13/1 (March 2023), 75-83. https://doi.org/10.33808/clinexphealthsci.1035133.
JAMA Hersek İ, Köroğlu MK, Coskunlu B, Ertaş B, Şener G, Ercan F. Apocynin Ameliorates Testicular Toxicity in High-Fat Diet-Fed Rats By Regulating Oxidative Stress. Clinical and Experimental Health Sciences. 2023;13:75–83.
MLA Hersek, İrem et al. “Apocynin Ameliorates Testicular Toxicity in High-Fat Diet-Fed Rats By Regulating Oxidative Stress”. Clinical and Experimental Health Sciences, vol. 13, no. 1, 2023, pp. 75-83, doi:10.33808/clinexphealthsci.1035133.
Vancouver Hersek İ, Köroğlu MK, Coskunlu B, Ertaş B, Şener G, Ercan F. Apocynin Ameliorates Testicular Toxicity in High-Fat Diet-Fed Rats By Regulating Oxidative Stress. Clinical and Experimental Health Sciences. 2023;13(1):75-83.

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