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PI3K AND MTOR IMMUNOREACTIVITY IN TESTICULAR TISSUE IN EXPERIMENTAL ALCOHOL ADDICTION MODEL

Year 2024, Volume: 13 Issue: 3, 1119 - 1124, 26.09.2024
https://doi.org/10.37989/gumussagbil.1412538

Abstract

Alcohol use disorder has negative effects on the reproductive system through the development of oxidative stress and its genotoxic effects on DNA integrity. Acute and chronic alcohol use adversely affects the male reproductive system. Phosphatidylinositol-3-kinase (PI3K) and mammalian target of rapamycin (mTOR) levels, which are involved in oxidative stress, may be important in the reproductive system in alcohol use disorder.
PI3K and mTOR immunoreactivities were evaluated in testicular tissue in an experimental acute and chronic alcohol intake model in male rats. Rats were divided into 3 groups as control male (n=7), acute male (n=7) and chronic male model (n=7). Histopathological analysis of testicular tissues taken from the experimental groups was performed by hematoxylin-eosin (H&E) staining. Then, testicular tissues of the experimental groups were dissected and PI3K and mTOR expressions were determined by immunohistochemistry method.
According to the H&E staining results, when the experimental groups were compared with the control group; It was observed that spermatozoa were less or absent in acute and chronic groups. mTOR and PI3K expressions were significantly increased in testicular tissues belonging to chronic and acute alcohol model groups. In the chronic alcohol model, both mTOR and PI3K expressions were significantly increased compared to the acute and control groups.
Our research reveal that PI3K and mTOR molecules, which are involved in oxidative stress in acute and chronic alcohol intake, may be associated with damage to the reproductive system. PI3K and mTOR proteins, can be targeted at the point of treatment against alcohol-induced reproductive damage.

References

  • 1. Witkiewitz, K., Litten, R.Z. and Leggio, L. (2019). “Advances in the science and treatment of alcohol use disorder”. Science advances, 5 (9), eaax4043.
  • 2. GBD 2016 Alcohol Collaborators (2018). “Alcohol use and burden for 195 countries and territories, 1990-2016: a systematic analysis for the Global Burden of Disease Study” 2016. Lancet (London, England), 392 (10152), 1015–1035.
  • 3. Finelli, R., Mottola, F. and Agarwal, A. (2021). “Impact of Alcohol Consumption on Male Fertility Potential: A Narrative Review”. International journal of environmental research and public health, 19 (1), 328.
  • 4. Dguzeh, U., Haddad, N.C., Smith, K.T.S., Johnson, J.O., Doye, A.A., Gwathmey, J.K. and Haddad, G.E. (2018). “Alcoholism: A Multi-Systemic Cellular Insult to Organs”. International journal of environmental research and public health, 15 (6), 1083.
  • 5. Iranpour, A. and Nakhaee, N. (2019). “A Review of Alcohol-Related Harms: A Recent Update”. Addiction & health, 11 (2), 129–137.
  • 6. Oremosu, A.A. and Akang, E.N. (2015). “Impact of alcohol on male reproductive hormones, oxidative stress and semen parameters in Sprague–Dawley rats”. Middle East Fertility Society Journal, 20 (2), 114-118.
  • 7. Pizzino, G., Irrera, N., Cucinotta, M., Pallio, G., Mannino, F., Arcoraci, V., Squadrito, F., Altavilla, D. and Bitto, A. (2017). “Oxidative Stress: Harms and Benefits for Human Health”. Oxidative medicine and cellular longevity, 2017, 8416763.
  • 8. Burton, GJ. and Jauniaux, E. (2011). “Oxidative stress. Best practice & research”. Clinical obstetrics & gynaecology, 25 (3), 287–299.
  • 9. Datta, S.R., Brunet, A. and Greenberg, M.E. (1999). “Cellular survival: a play in three Akts”. Genes & development, 13 (22), 2905–2927.
  • 10. Ersahin, T., Tuncbag, N. and Cetin-Atalay, R. (2015). “The PI3K/AKT/mTOR interactive pathway”. Molecular bioSystems, 11 (7), 1946–1954.
  • 11. Liu, G.Y. and Sabatini, D.M. (2020). “mTOR at the nexus of nutrition, growth, ageing and disease”. Nature reviews. Molecular cell biology, 21 (4), 183–203.
  • 12. Tsermpini, E.E., Plemenitaš Ilješ, A. and Dolžan, V. (2022). “Alcohol-Induced Oxidative Stress and the Role of Antioxidants in Alcohol Use Disorder: A Systematic Review”. Antioxidants (Basel, Switzerland), 11 (7), 1374.
  • 13. Emanuele, M.A. and Emanuele, N. (2001). “Alcohol and the male reproductive system”. Alcohol research & health : the journal of the National Institute on Alcohol Abuse and Alcoholism, 25 (4), 282–287.
  • 14. Das, S.K. and Vasudevan, D.M. (2007). “Alcohol-induced oxidative stress”. Life sciences, 81 (3), 177–187.
  • 15. Ogilvie, K.M. and Rivier, C. (1997). “Gender difference in hypothalamic-pituitary-adrenal axis response to alcohol in the rat: activational role of gonadal steroids”. Brain research, 766 (1-2), 19–28.
  • 16. Nguyen, T.M.T., Steane, S.E., Moritz, K.M. and Akison, L.K. (2019). “Prenatal alcohol exposure programmes offspring disease: insulin resistance in adult males in a rat model of acute exposure”. The Journal of physiology, 597 (23), 5619–5637.
  • 17. McCormack, C., Hutchinson, D., Burns, L., Wilson, J., Elliott, E., Allsop, S., Najman, J., Jacobs, S., Rossen, L., Olsson, C. and Mattick, R. (2017). “Prenatal Alcohol Consumption Between Conception and Recognition of Pregnancy”. Alcoholism, clinical and experimental research, 41 (2), 369–378.
  • 18. Muggli, E., O’Leary, C., Donath, S., Orsini, F., Forster, D., Anderson, P.J. and Halliday, J. (2016). “Did you ever drink more?” A detailed description of pregnant women’s drinking patterns. BMC Public Health, 16 (1), 1-13.
  • 19. Bonthius, D.J. and West, J.R. (1990). “Alcohol-induced neuronal loss in developing rats: increased brain damage with binge exposure”. Alcoholism, clinical and experimental research, 14 (1), 107–118.
  • 20. Xu, L.Z., He, K.X., Ning, J.Z. and Cheng, F. (2022). “Oleuropein attenuates testicular ischemia-reperfusion by inhibiting apoptosis and inflammation”. Tissue & cell, 78, 101876.
  • 21. Okan, A., Doğanyiğit, Z., Eroğlu, E., Akyüz, E. ve Demir, N. (2021). “Immunoreactive definition of TNF- α, HIF-1 α, Kir6.2, Kir3.1 and M2 muscarinic receptor for cardiac and pancreatic tissues in a mouse model for type 1 diabetes”. Life sciences, 284, 119886.
  • 22. Kovacic, P. (2005). “Unifying mechanism for addiction and toxicity of abused drugs with application to dopamine and glutamate mediators: electron transfer and reactive oxygen species”. Medical hypotheses, 65 (1), 90–96. 23. Toda, N. and Ayajiki, K. (2010). “Vascular actions of nitric oxide as affected by exposure to alcohol”. Alcohol and alcoholism (Oxford, Oxfordshire), 45 (4), 347–355.
  • 24. Agarwal, A., Aponte-Mellado, A., Premkumar, B.J., Shaman, A. and Gupta, S. (2012). “The effects of oxidative stress on female reproduction: a review”. Reproductive biology and endocrinology, 10, 49.
  • 25. Çanıllıoğlu, Y.E. and Ercan, F. (2011). “In utero etanol uygulamasının sıçan testis morfolojisi üzerine etkileri”. Acıbadem Üniversitesi Sağlık Bilimleri Dergisi 1, 10-16.
  • 26. El-Sokkary, G.H. (2001). “Quantitative study on the effects of chronic ethanol administration on the testis of adult male rat”. Neuro endocrinology letters, 22 (2), 93–99.
  • 27. Salonen, I. and Huhtaniemi, I. (1990). “Effects of chronic ethanol diet on pituitary-testicular function of the rat”. Biology of reproduction, 42 (1), 55-62.
  • 28. Koh, P.O. and Kim, M.O. (2006). “Ethanol exposure decreases cell proliferation and increases apoptosis in rat testes”. The Journal of veterinary medical science, 68 (10), 1013–1017.
  • 29. Correia-Branco, A., Keating, E. and Martel, F. (2018). “Involvement of mTOR, JNK and PI3K in the negative effect of ethanol and metformin on the human first-trimester extravillous trophoblast HTR-8/SVneo cell line". European journal of pharmacology, 833, 16–24.
  • 30. Reichman, M.E., Judd, J.T., Longcope, C., Schatzkin, A., Clevidence, B.A., Nair, P.P., Campbell, W.S. and Taylor, P.R. (1993). “Effects of alcohol consumption on plasma and urinary hormone concentrations in premenopausal women”. Journal of the National Cancer Institute, 85 (9), 722–727.
  • 31. Taylor, K.C., Small, C.M., Dominguez, C.E., Murray, L.E., Tang, W., Wilson, M.M. and Marcus, M. (2011). “Alcohol, smoking, and caffeine in relation to fecundability, with effect modification by NAT2”. Annals of epidemiology, 21 (11), 864-872.
  • 32. Goedde, H.W., Agarwal, D.P., Fritze, G., Meier-Tackmann, D., Singh, S., Beckmann, G., Bhatia, K., Chen, L.Z., Fang, B. and Lisker, R. (1992). “Distribution of ADH2 and ALDH2 genotypes in different populations”. Human genetics, 88 (3), 344–346.

DENEYSEL ALKOL BAĞIMLILIĞI MODELİNDE TESTİS DOKUSUNDA PI3K VE MTOR İMMÜNOREAKTİVİTESİ

Year 2024, Volume: 13 Issue: 3, 1119 - 1124, 26.09.2024
https://doi.org/10.37989/gumussagbil.1412538

Abstract

Alkol kullanım bozukluğu, oksidatif stresin gelişmesi ve bunun DNA bütünlüğü üzerindeki genotoksik etkileri yoluyla üreme sistemi üzerinde olumsuz etkilere sahiptir. Akut ve kronik alkol kullanımı erkek üreme sistemini olumsuz etkiler. Oksidatif streste rol oynayan fosfatidilinositol-3-kinaz (PI3K) ve rapamisin memeli hedefi (mTOR) düzeyleri, alkol kullanım bozukluğunda üreme sistemi açısından önemli olabilir.
PI3K ve mTOR immünoreaktiviteleri, erkek sıçanlarda deneysel bir akut ve kronik alkol alımı modelinde testis dokusunda değerlendirildi. Sıçanlar kontrol erkek (n=7), akut erkek (n=7) ve kronik erkek model (n=7) olmak üzere 3 gruba ayrıldı. Deney gruplarından alınan testis dokularının histopatolojik analizi hematoksilen-eozin (H&E) boyama ile yapıldı. Daha sonra deney gruplarının testis dokuları diseke edilerek immünohistokimya yöntemiyle PI3K ve mTOR ekspresyonları belirlendi.
H&E boyama sonuçlarına göre deney grupları kontrol grubu ile karşılaştırıldığında; Akut ve kronik gruplarda spermatozoanın az olduğu veya hiç olmadığı görüldü. Kronik ve akut alkol model gruplarına ait testis dokularında mTOR ve PI3K ekspresyonları anlamlı derecede arttı. Kronik alkol modelinde hem mTOR hem de PI3K ekspresyonları akut ve kontrol gruplarına göre anlamlı derecede arttı.
Araştırmamız, akut ve kronik alkol alımında oksidatif strese karışan PI3K ve mTOR moleküllerinin üreme sistemindeki hasarla ilişkili olabileceğini ortaya koymaktadır. PI3K ve mTOR proteinleri, alkole bağlı üreme hasarına karşı tedavi noktasında hedeflenebilir.

References

  • 1. Witkiewitz, K., Litten, R.Z. and Leggio, L. (2019). “Advances in the science and treatment of alcohol use disorder”. Science advances, 5 (9), eaax4043.
  • 2. GBD 2016 Alcohol Collaborators (2018). “Alcohol use and burden for 195 countries and territories, 1990-2016: a systematic analysis for the Global Burden of Disease Study” 2016. Lancet (London, England), 392 (10152), 1015–1035.
  • 3. Finelli, R., Mottola, F. and Agarwal, A. (2021). “Impact of Alcohol Consumption on Male Fertility Potential: A Narrative Review”. International journal of environmental research and public health, 19 (1), 328.
  • 4. Dguzeh, U., Haddad, N.C., Smith, K.T.S., Johnson, J.O., Doye, A.A., Gwathmey, J.K. and Haddad, G.E. (2018). “Alcoholism: A Multi-Systemic Cellular Insult to Organs”. International journal of environmental research and public health, 15 (6), 1083.
  • 5. Iranpour, A. and Nakhaee, N. (2019). “A Review of Alcohol-Related Harms: A Recent Update”. Addiction & health, 11 (2), 129–137.
  • 6. Oremosu, A.A. and Akang, E.N. (2015). “Impact of alcohol on male reproductive hormones, oxidative stress and semen parameters in Sprague–Dawley rats”. Middle East Fertility Society Journal, 20 (2), 114-118.
  • 7. Pizzino, G., Irrera, N., Cucinotta, M., Pallio, G., Mannino, F., Arcoraci, V., Squadrito, F., Altavilla, D. and Bitto, A. (2017). “Oxidative Stress: Harms and Benefits for Human Health”. Oxidative medicine and cellular longevity, 2017, 8416763.
  • 8. Burton, GJ. and Jauniaux, E. (2011). “Oxidative stress. Best practice & research”. Clinical obstetrics & gynaecology, 25 (3), 287–299.
  • 9. Datta, S.R., Brunet, A. and Greenberg, M.E. (1999). “Cellular survival: a play in three Akts”. Genes & development, 13 (22), 2905–2927.
  • 10. Ersahin, T., Tuncbag, N. and Cetin-Atalay, R. (2015). “The PI3K/AKT/mTOR interactive pathway”. Molecular bioSystems, 11 (7), 1946–1954.
  • 11. Liu, G.Y. and Sabatini, D.M. (2020). “mTOR at the nexus of nutrition, growth, ageing and disease”. Nature reviews. Molecular cell biology, 21 (4), 183–203.
  • 12. Tsermpini, E.E., Plemenitaš Ilješ, A. and Dolžan, V. (2022). “Alcohol-Induced Oxidative Stress and the Role of Antioxidants in Alcohol Use Disorder: A Systematic Review”. Antioxidants (Basel, Switzerland), 11 (7), 1374.
  • 13. Emanuele, M.A. and Emanuele, N. (2001). “Alcohol and the male reproductive system”. Alcohol research & health : the journal of the National Institute on Alcohol Abuse and Alcoholism, 25 (4), 282–287.
  • 14. Das, S.K. and Vasudevan, D.M. (2007). “Alcohol-induced oxidative stress”. Life sciences, 81 (3), 177–187.
  • 15. Ogilvie, K.M. and Rivier, C. (1997). “Gender difference in hypothalamic-pituitary-adrenal axis response to alcohol in the rat: activational role of gonadal steroids”. Brain research, 766 (1-2), 19–28.
  • 16. Nguyen, T.M.T., Steane, S.E., Moritz, K.M. and Akison, L.K. (2019). “Prenatal alcohol exposure programmes offspring disease: insulin resistance in adult males in a rat model of acute exposure”. The Journal of physiology, 597 (23), 5619–5637.
  • 17. McCormack, C., Hutchinson, D., Burns, L., Wilson, J., Elliott, E., Allsop, S., Najman, J., Jacobs, S., Rossen, L., Olsson, C. and Mattick, R. (2017). “Prenatal Alcohol Consumption Between Conception and Recognition of Pregnancy”. Alcoholism, clinical and experimental research, 41 (2), 369–378.
  • 18. Muggli, E., O’Leary, C., Donath, S., Orsini, F., Forster, D., Anderson, P.J. and Halliday, J. (2016). “Did you ever drink more?” A detailed description of pregnant women’s drinking patterns. BMC Public Health, 16 (1), 1-13.
  • 19. Bonthius, D.J. and West, J.R. (1990). “Alcohol-induced neuronal loss in developing rats: increased brain damage with binge exposure”. Alcoholism, clinical and experimental research, 14 (1), 107–118.
  • 20. Xu, L.Z., He, K.X., Ning, J.Z. and Cheng, F. (2022). “Oleuropein attenuates testicular ischemia-reperfusion by inhibiting apoptosis and inflammation”. Tissue & cell, 78, 101876.
  • 21. Okan, A., Doğanyiğit, Z., Eroğlu, E., Akyüz, E. ve Demir, N. (2021). “Immunoreactive definition of TNF- α, HIF-1 α, Kir6.2, Kir3.1 and M2 muscarinic receptor for cardiac and pancreatic tissues in a mouse model for type 1 diabetes”. Life sciences, 284, 119886.
  • 22. Kovacic, P. (2005). “Unifying mechanism for addiction and toxicity of abused drugs with application to dopamine and glutamate mediators: electron transfer and reactive oxygen species”. Medical hypotheses, 65 (1), 90–96. 23. Toda, N. and Ayajiki, K. (2010). “Vascular actions of nitric oxide as affected by exposure to alcohol”. Alcohol and alcoholism (Oxford, Oxfordshire), 45 (4), 347–355.
  • 24. Agarwal, A., Aponte-Mellado, A., Premkumar, B.J., Shaman, A. and Gupta, S. (2012). “The effects of oxidative stress on female reproduction: a review”. Reproductive biology and endocrinology, 10, 49.
  • 25. Çanıllıoğlu, Y.E. and Ercan, F. (2011). “In utero etanol uygulamasının sıçan testis morfolojisi üzerine etkileri”. Acıbadem Üniversitesi Sağlık Bilimleri Dergisi 1, 10-16.
  • 26. El-Sokkary, G.H. (2001). “Quantitative study on the effects of chronic ethanol administration on the testis of adult male rat”. Neuro endocrinology letters, 22 (2), 93–99.
  • 27. Salonen, I. and Huhtaniemi, I. (1990). “Effects of chronic ethanol diet on pituitary-testicular function of the rat”. Biology of reproduction, 42 (1), 55-62.
  • 28. Koh, P.O. and Kim, M.O. (2006). “Ethanol exposure decreases cell proliferation and increases apoptosis in rat testes”. The Journal of veterinary medical science, 68 (10), 1013–1017.
  • 29. Correia-Branco, A., Keating, E. and Martel, F. (2018). “Involvement of mTOR, JNK and PI3K in the negative effect of ethanol and metformin on the human first-trimester extravillous trophoblast HTR-8/SVneo cell line". European journal of pharmacology, 833, 16–24.
  • 30. Reichman, M.E., Judd, J.T., Longcope, C., Schatzkin, A., Clevidence, B.A., Nair, P.P., Campbell, W.S. and Taylor, P.R. (1993). “Effects of alcohol consumption on plasma and urinary hormone concentrations in premenopausal women”. Journal of the National Cancer Institute, 85 (9), 722–727.
  • 31. Taylor, K.C., Small, C.M., Dominguez, C.E., Murray, L.E., Tang, W., Wilson, M.M. and Marcus, M. (2011). “Alcohol, smoking, and caffeine in relation to fecundability, with effect modification by NAT2”. Annals of epidemiology, 21 (11), 864-872.
  • 32. Goedde, H.W., Agarwal, D.P., Fritze, G., Meier-Tackmann, D., Singh, S., Beckmann, G., Bhatia, K., Chen, L.Z., Fang, B. and Lisker, R. (1992). “Distribution of ADH2 and ALDH2 genotypes in different populations”. Human genetics, 88 (3), 344–346.
There are 31 citations in total.

Details

Primary Language English
Subjects Food Properties, Clinical Chemistry, Metabolic Medicine
Journal Section Original Article
Authors

Osman Öztürk 0000-0003-1156-7419

Aslı Okan Oflamaz 0000-0001-8152-7338

Mustafa Kurt 0000-0002-9017-9643

Ece Eroğlu 0000-0001-6385-479X

Seher Yilmaz 0000-0003-4551-995X

A. Cihangir Uğuz 0000-0002-5778-581X

Mert Ocak 0000-0001-6832-6208

Züleyha Doğanyiğit 0000-0002-6980-3384

Publication Date September 26, 2024
Submission Date December 31, 2023
Acceptance Date September 9, 2024
Published in Issue Year 2024 Volume: 13 Issue: 3

Cite

APA Öztürk, O., Okan Oflamaz, A., Kurt, M., Eroğlu, E., et al. (2024). PI3K AND MTOR IMMUNOREACTIVITY IN TESTICULAR TISSUE IN EXPERIMENTAL ALCOHOL ADDICTION MODEL. Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi, 13(3), 1119-1124. https://doi.org/10.37989/gumussagbil.1412538
AMA Öztürk O, Okan Oflamaz A, Kurt M, Eroğlu E, Yilmaz S, Uğuz AC, Ocak M, Doğanyiğit Z. PI3K AND MTOR IMMUNOREACTIVITY IN TESTICULAR TISSUE IN EXPERIMENTAL ALCOHOL ADDICTION MODEL. Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi. September 2024;13(3):1119-1124. doi:10.37989/gumussagbil.1412538
Chicago Öztürk, Osman, Aslı Okan Oflamaz, Mustafa Kurt, Ece Eroğlu, Seher Yilmaz, A. Cihangir Uğuz, Mert Ocak, and Züleyha Doğanyiğit. “PI3K AND MTOR IMMUNOREACTIVITY IN TESTICULAR TISSUE IN EXPERIMENTAL ALCOHOL ADDICTION MODEL”. Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi 13, no. 3 (September 2024): 1119-24. https://doi.org/10.37989/gumussagbil.1412538.
EndNote Öztürk O, Okan Oflamaz A, Kurt M, Eroğlu E, Yilmaz S, Uğuz AC, Ocak M, Doğanyiğit Z (September 1, 2024) PI3K AND MTOR IMMUNOREACTIVITY IN TESTICULAR TISSUE IN EXPERIMENTAL ALCOHOL ADDICTION MODEL. Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi 13 3 1119–1124.
IEEE O. Öztürk, “PI3K AND MTOR IMMUNOREACTIVITY IN TESTICULAR TISSUE IN EXPERIMENTAL ALCOHOL ADDICTION MODEL”, Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi, vol. 13, no. 3, pp. 1119–1124, 2024, doi: 10.37989/gumussagbil.1412538.
ISNAD Öztürk, Osman et al. “PI3K AND MTOR IMMUNOREACTIVITY IN TESTICULAR TISSUE IN EXPERIMENTAL ALCOHOL ADDICTION MODEL”. Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi 13/3 (September 2024), 1119-1124. https://doi.org/10.37989/gumussagbil.1412538.
JAMA Öztürk O, Okan Oflamaz A, Kurt M, Eroğlu E, Yilmaz S, Uğuz AC, Ocak M, Doğanyiğit Z. PI3K AND MTOR IMMUNOREACTIVITY IN TESTICULAR TISSUE IN EXPERIMENTAL ALCOHOL ADDICTION MODEL. Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi. 2024;13:1119–1124.
MLA Öztürk, Osman et al. “PI3K AND MTOR IMMUNOREACTIVITY IN TESTICULAR TISSUE IN EXPERIMENTAL ALCOHOL ADDICTION MODEL”. Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi, vol. 13, no. 3, 2024, pp. 1119-24, doi:10.37989/gumussagbil.1412538.
Vancouver Öztürk O, Okan Oflamaz A, Kurt M, Eroğlu E, Yilmaz S, Uğuz AC, Ocak M, Doğanyiğit Z. PI3K AND MTOR IMMUNOREACTIVITY IN TESTICULAR TISSUE IN EXPERIMENTAL ALCOHOL ADDICTION MODEL. Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi. 2024;13(3):1119-24.