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Modulatory Role of Hypericum perforatum on Oxidative Stress and Histopathological Changes in Ethanol-Exposed Rat Ovaries

Yıl 2025, Cilt: 36 Sayı: 3, 169 - 175, 30.11.2025
https://doi.org/10.36483/vanvetj.1691968

Öz

In this study, the possible protective effect of Hypericum perforatum extract (HPE) against ethanol induced ovarian damage was investigated. Rats were allocated into four groups: Group I; Control, Group II (HPE); Rats treated with 200 mg/kg b.w. Group III (Alcoholic); Rats treated with 2.5 g/kg b.w. Group IV (Alcohol+HPE); Alcoholic rats treated with 200 mg/kg b.w. Thiobarbituric acid reactive substances (TBARS), catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD), levels were measured in ovarian tissues to determine the antioxidative effects of HPE. The histology of the ovarian was examined using hematoxylin & eosin, periodic acid Schiff, masson trichrome and amyloid staining methods. Mechanistically, the ovary of ethanol treated rats exhibited a significant increase in the levels of TBARS and a significant decrease in the levels of GPx, CAT and SOD. We concluded that HPE has a protective effect on ovarian tissue. Interestingly, oral supplementation of ethanol treated rats with HPE significantly abolished collagen deposition, abrogated oxidative stress, and hence repaired the ovarian architecture nearly to the normal architecture observed in the control rats. Our study implicates that HPE has a protective potential against ethanol induced ovarian injury, which might be strongly associated with the induction of oxidative stress arising from ethanol consumption.

Etik Beyan

All animal manipulations were performed according to the in conformity with the Institutional Ethical Committee for Animal Care and Use at Atatürk University (protocol number: (54826478-E.1900181803/24.06.2019) and the Guide for the Care and Use of Laboratory Animals.

Kaynakça

  • Abd El Motteleb DM, Abd El Aleem DI (2017). Renoprotective effect of Hypericum perforatum against diabetic nephropathy in rats: Insights in the underlying mechanisms. Clin Exp Pharmacol Physiol, 44 (4), 509-521.
  • Agapouda A, Booker A, Kiss T et al. (2019). Quality control of Hypericum perforatum L. analytical challenges and recent progress. J Pharm Pharmacol, 71 (1), 15-37.
  • Aitken RJ. (2020). Impact of oxidative stress on male and female reproduction: a comparative review. Repro, 159 (5), 189-201.
  • Al-Basher GI, Alkahtani S, Al-Harbi NO et al. (2021). Oxidative stress and histopathological changes in reproductive organs of female rats exposed to ethanol. Saudi J Biol Sci, 28 (7), 3846–3853.
  • Anderson K, Nisenblat V, Norman R (2010). Lifestyle factors in people seeking infertility treatment - A review. Aust N Z J Obstet Gynaecol, 50 (1), 8-20.
  • Apaydin EA, Maher AR, Shanman R et al. (2020). A systematic review of Hypericum perforatum for the treatment of depression. J Affect Disord, 266, 749-761.
  • Arokiyaraj S, Balamurugan R, Augustian P (2011). Antihyperglycemic effect of Hypericum perforatum ethyl acetate extract on streptozotocin-induced diabetic rats. Asian Pac J Trop Biomed, 1 (5), 386-390.
  • Avila DV, Myers SA, Zhang J et al. (2017). Phosphodiesterase 4b expression plays a major role in alcohol-induced neuro-inflammation. Neuropharmacol, 125, 376-385.
  • Buján GE, Serra HA, Molina SJ, Guelman LR (2019). Prevention of Brain Damage Triggered by Alcohol Consumption during Adolescence: Focus on Oxidative Stress. Current Pharm Desing, 25 (45), 4782-4790.
  • Cakir M, Duzova H, Baysal I et al. (2017). The effect of hypericum perforatum on kidney ischemia/reperfusion damage. Ren Fail, 39 (1), 385-391.
  • Chuffa LG, Amorim JP, Teixeira GR et al. (2011). Long-term exogenous melatonin treatment modulates overall feed efficiency and protects ovarian tissue against injuries caused by ethanol-induced oxidative stress in adult UChB rats. Alcohol Clin Exp Res, 35 (8), 1498-508.
  • Combs AB, Acosta D (1990). Toxic mechanisms of the heart: a review. Toxicol Pathol, 18 (4), 583-596.
  • Demirci T, Kaya E, Uzun FG (2019). Adverse effects of Hypericum perforatum on reproductive parameters in experimental models. J Ethnopharmacol. 239, 111–118.
  • Distler JHW, Györfi AH, Ramanujam M et al. (2019). Shared and distinct mechanisms of fibrosis. Nat Rev Rheumatol. 15, 705–730.
  • Ezzat Ahmed M, Ibrahim WM, El-Ghoneimy A (2020). Ethanol-induced reproductive toxicity: oxidative stress and apoptotic changes in rat ovary. Environ Toxicol Pharmacol, 80, e103449. Fang X, Zhang Y, Wang J et al. (2023). Ethanol-induced oxidative stress contributes to endothelial dysfunction and cardiovascular injury. Toxicol Appl Pharmacol, 462, 116423.
  • Ferreira SE, Abrahao KP, Souza-Formigoni ML (2013). Expression of behavioral sensitization to ethanol is increased by energy drink administration. Pharmacol Biochem Behav, 110, 245-248.
  • Gharaee-Kermani M, Rodriguez-Nieves JA, Mehra R et al. (2013). Obesity-induced diabetes and lower urinary tract fibrosis promote urinary voiding dysfunction in a mouse model. The Prostate, 73 (10), 1123-1133.
  • Guo R, Ren J (2021). Alcohol and acetaldehyde in public health: from biochemical mechanisms to clinical implications. World J Gastroenterol, 27 (19), 2305–2322.
  • Henderson NC, Rieder F, Wynn TA (2020). Fibrosis: from mechanisms to medicines. Nature, 587, 555–566.
  • Hosseinzadeh H, Karimi G, Ameri M (2021). Protective effects of Hypericum perforatum against oxidative damage: molecular mechanisms and clinical perspectives. Phytomedicine. 86, e153567.
  • Khazdair MR, Boskabady MH, Hosseini M, Rezaee R (2020). Toxicological effects of Hypericum perforatum (St. John’s Wort): A review. Phytother Res, 34 (10), 2522-2534.
  • Kim HG, Huang M, Xin Y et al. (2019). The epigenetic regulator SIRT6 protects the liver from alcohol-induced tissue injury by reducing oxidative stress in mice. J Hepatol. 71 (5), 960-969.
  • Kisseleva T, Brenner DA (2021). Mechanisms of fibrogenesis. Exp Biol Med (Maywood), 246 (6), 580–586.
  • Koukopoulos A, Sani G, Koukopoulos AE (2021). Hypericum perforatum in psychiatry: Antidepressant effect and beyond. CNS Drugs, 35 (8), 853-867.
  • Kumar S, Singh R, Meena R (2021). Oxidative stress-mediated organ toxicity induced by alcohol and the protective role of dietary antioxidants. Biomed Pharmacother, 142, e112046.
  • Li H, Zhou Q, Song X et al. (2022). Chronic alcohol exposure impairs ovarian function via oxidative stress and inflammation pathways. Toxicol Rep, 9, 887-896.
  • Müller WE, Singer A, Wonnemann M, Hafner U (2020). Hyperforin – A key constituent of Hypericum perforatum in the treatment of depression and related disorders. Pharmacol Res, 161, e105216.
  • Napoli E, Siracusa L, Ruberto G et al. (2018). Phytochemical profiles, phototoxic and antioxidant properties of eleven Hypericum species - A comparative study. Phytochem, 152, 162-173.
  • OECD. (2020). OECD Guidelines for the Testing of Chemicals, Section 423: Acute Oral Toxicity Acute Toxic Class Method. OECD Publishing, Paris.
  • Qin L, Chen Y, Wang X et al. (2023). Alcohol exposure induces oxidative stress and mitochondrial dysfunction in the liver: protective role of natural antioxidants. Front Pharmacol, 14, e1112345. Sharma A, Kumar A, Singh M (2023). Hypericum perforatum: A phytopharmacological update on mechanisms of action in oxidative stress and inflammation. Front Pharmacol, 14, e1145897. Sies H, Berndt C, Jones DP (2022). Oxidative stress. Annu Rev Biochem, 91, 719–760.
  • Stangl V, Lorenz M, Ludwig A, Stangl K (2022). Alcohol, oxidative stress and female reproductive health: new insights. Biomed Pharmacother, 152, 113222.
  • Verma S, Ranawat P, Sharma N, Nehru B (2019). Ginko biloba attenuates aluminum lactate-induced neurotoxicity in reproductive senescent female rats: behavioral, biochemical, and histopathological study. Environ Sci Pollut Res Int.26 (26), 27148 - 27167.
  • Yang S, Wang Y, Zhang Y et al. (2022). Oxidative stress and female infertility: mechanisms and management. Reprod Biol Endocrinol. 20, 65.
  • Zhang Y, Liu H, Wang L et al. (2021). Ethanol-induced oxidative stress and apoptosis in rat ovaries: involvement of mitochondrial dysfunction. Reprod Toxicol, 100, 56-65.
  • Zhou Y, Li X, Zhao C et al. (2022). Ethanol triggers excessive ROS generation and disrupts redox homeostasis in neuronal cells. Neurochem Res, 47, 2215–2228.

Hypericum perforatum'un Etanole Maruz Kalan Sıçan Yumurtalıklarında Oksidatif Stres ve Histopatolojik Değişiklikler Üzerindeki Düzenleyici Rolü

Yıl 2025, Cilt: 36 Sayı: 3, 169 - 175, 30.11.2025
https://doi.org/10.36483/vanvetj.1691968

Öz

Bu çalışmada, Hypericum perforatum ekstraktının (HPE) etanol kaynaklı over hasarına karşı olası koruyucu etkisi araştırıldı. Sıçanlar dört gruba ayrıldı: Grup I; kontrol, Grup II (HPE); 200 mg/kg vücut ağırlığı ile tedavi edilen sıçanlar, Grup III (Alkollü); 2.5 g/kg vücut ağırlığı ile tedavi edilen sıçanlar, Grup IV (Alkol+HPE); 200 mg/kg vücut ağırlığı ile tedavi edilen alkollü sıçanlar. HPE'nin antioksidan etkilerini belirlemek için over dokularında tiyobarbitürik asit reaktif maddeler (TBARS), katalaz (CAT), glutatyon peroksidaz (GPx) ve süperoksit dismutaz (SOD) düzeyleri ölçüldü. Overin histolojisi hematoksilen & eozin, periyodik asit Schiff, masson trikrom ve amiloid boyama yöntemleri kullanılarak incelendi. Mekanik olarak, etanol ile tedavi edilen sıçanların yumurtalıkları TBARS seviyelerinde önemli bir artış ve GPx, CAT ve SOD seviyelerinde önemli bir azalma gösterdi. HPE'nin yumurtalık dokusu üzerinde koruyucu bir etkiye sahip olduğu sonucuna vardık. İlginç bir şekilde, etanol ile tedavi edilen sıçanlara HPE ile oral takviye, kolajen birikimini önemli ölçüde ortadan kaldırdı, oksidatif stresi ortadan kaldırdı ve dolayısıyla yumurtalık yapısını kontrol sıçanlarında gözlemlenen normal yapıya yakın bir şekilde onardı. Çalışmamız, HPE'nin etanol kaynaklı yumurtalık hasarına karşı koruyucu bir potansiyele sahip olduğunu ve bunun etanol tüketiminden kaynaklanan oksidatif stresin indüklenmesiyle güçlü bir şekilde ilişkili olabileceğini ima etmektedir.

Kaynakça

  • Abd El Motteleb DM, Abd El Aleem DI (2017). Renoprotective effect of Hypericum perforatum against diabetic nephropathy in rats: Insights in the underlying mechanisms. Clin Exp Pharmacol Physiol, 44 (4), 509-521.
  • Agapouda A, Booker A, Kiss T et al. (2019). Quality control of Hypericum perforatum L. analytical challenges and recent progress. J Pharm Pharmacol, 71 (1), 15-37.
  • Aitken RJ. (2020). Impact of oxidative stress on male and female reproduction: a comparative review. Repro, 159 (5), 189-201.
  • Al-Basher GI, Alkahtani S, Al-Harbi NO et al. (2021). Oxidative stress and histopathological changes in reproductive organs of female rats exposed to ethanol. Saudi J Biol Sci, 28 (7), 3846–3853.
  • Anderson K, Nisenblat V, Norman R (2010). Lifestyle factors in people seeking infertility treatment - A review. Aust N Z J Obstet Gynaecol, 50 (1), 8-20.
  • Apaydin EA, Maher AR, Shanman R et al. (2020). A systematic review of Hypericum perforatum for the treatment of depression. J Affect Disord, 266, 749-761.
  • Arokiyaraj S, Balamurugan R, Augustian P (2011). Antihyperglycemic effect of Hypericum perforatum ethyl acetate extract on streptozotocin-induced diabetic rats. Asian Pac J Trop Biomed, 1 (5), 386-390.
  • Avila DV, Myers SA, Zhang J et al. (2017). Phosphodiesterase 4b expression plays a major role in alcohol-induced neuro-inflammation. Neuropharmacol, 125, 376-385.
  • Buján GE, Serra HA, Molina SJ, Guelman LR (2019). Prevention of Brain Damage Triggered by Alcohol Consumption during Adolescence: Focus on Oxidative Stress. Current Pharm Desing, 25 (45), 4782-4790.
  • Cakir M, Duzova H, Baysal I et al. (2017). The effect of hypericum perforatum on kidney ischemia/reperfusion damage. Ren Fail, 39 (1), 385-391.
  • Chuffa LG, Amorim JP, Teixeira GR et al. (2011). Long-term exogenous melatonin treatment modulates overall feed efficiency and protects ovarian tissue against injuries caused by ethanol-induced oxidative stress in adult UChB rats. Alcohol Clin Exp Res, 35 (8), 1498-508.
  • Combs AB, Acosta D (1990). Toxic mechanisms of the heart: a review. Toxicol Pathol, 18 (4), 583-596.
  • Demirci T, Kaya E, Uzun FG (2019). Adverse effects of Hypericum perforatum on reproductive parameters in experimental models. J Ethnopharmacol. 239, 111–118.
  • Distler JHW, Györfi AH, Ramanujam M et al. (2019). Shared and distinct mechanisms of fibrosis. Nat Rev Rheumatol. 15, 705–730.
  • Ezzat Ahmed M, Ibrahim WM, El-Ghoneimy A (2020). Ethanol-induced reproductive toxicity: oxidative stress and apoptotic changes in rat ovary. Environ Toxicol Pharmacol, 80, e103449. Fang X, Zhang Y, Wang J et al. (2023). Ethanol-induced oxidative stress contributes to endothelial dysfunction and cardiovascular injury. Toxicol Appl Pharmacol, 462, 116423.
  • Ferreira SE, Abrahao KP, Souza-Formigoni ML (2013). Expression of behavioral sensitization to ethanol is increased by energy drink administration. Pharmacol Biochem Behav, 110, 245-248.
  • Gharaee-Kermani M, Rodriguez-Nieves JA, Mehra R et al. (2013). Obesity-induced diabetes and lower urinary tract fibrosis promote urinary voiding dysfunction in a mouse model. The Prostate, 73 (10), 1123-1133.
  • Guo R, Ren J (2021). Alcohol and acetaldehyde in public health: from biochemical mechanisms to clinical implications. World J Gastroenterol, 27 (19), 2305–2322.
  • Henderson NC, Rieder F, Wynn TA (2020). Fibrosis: from mechanisms to medicines. Nature, 587, 555–566.
  • Hosseinzadeh H, Karimi G, Ameri M (2021). Protective effects of Hypericum perforatum against oxidative damage: molecular mechanisms and clinical perspectives. Phytomedicine. 86, e153567.
  • Khazdair MR, Boskabady MH, Hosseini M, Rezaee R (2020). Toxicological effects of Hypericum perforatum (St. John’s Wort): A review. Phytother Res, 34 (10), 2522-2534.
  • Kim HG, Huang M, Xin Y et al. (2019). The epigenetic regulator SIRT6 protects the liver from alcohol-induced tissue injury by reducing oxidative stress in mice. J Hepatol. 71 (5), 960-969.
  • Kisseleva T, Brenner DA (2021). Mechanisms of fibrogenesis. Exp Biol Med (Maywood), 246 (6), 580–586.
  • Koukopoulos A, Sani G, Koukopoulos AE (2021). Hypericum perforatum in psychiatry: Antidepressant effect and beyond. CNS Drugs, 35 (8), 853-867.
  • Kumar S, Singh R, Meena R (2021). Oxidative stress-mediated organ toxicity induced by alcohol and the protective role of dietary antioxidants. Biomed Pharmacother, 142, e112046.
  • Li H, Zhou Q, Song X et al. (2022). Chronic alcohol exposure impairs ovarian function via oxidative stress and inflammation pathways. Toxicol Rep, 9, 887-896.
  • Müller WE, Singer A, Wonnemann M, Hafner U (2020). Hyperforin – A key constituent of Hypericum perforatum in the treatment of depression and related disorders. Pharmacol Res, 161, e105216.
  • Napoli E, Siracusa L, Ruberto G et al. (2018). Phytochemical profiles, phototoxic and antioxidant properties of eleven Hypericum species - A comparative study. Phytochem, 152, 162-173.
  • OECD. (2020). OECD Guidelines for the Testing of Chemicals, Section 423: Acute Oral Toxicity Acute Toxic Class Method. OECD Publishing, Paris.
  • Qin L, Chen Y, Wang X et al. (2023). Alcohol exposure induces oxidative stress and mitochondrial dysfunction in the liver: protective role of natural antioxidants. Front Pharmacol, 14, e1112345. Sharma A, Kumar A, Singh M (2023). Hypericum perforatum: A phytopharmacological update on mechanisms of action in oxidative stress and inflammation. Front Pharmacol, 14, e1145897. Sies H, Berndt C, Jones DP (2022). Oxidative stress. Annu Rev Biochem, 91, 719–760.
  • Stangl V, Lorenz M, Ludwig A, Stangl K (2022). Alcohol, oxidative stress and female reproductive health: new insights. Biomed Pharmacother, 152, 113222.
  • Verma S, Ranawat P, Sharma N, Nehru B (2019). Ginko biloba attenuates aluminum lactate-induced neurotoxicity in reproductive senescent female rats: behavioral, biochemical, and histopathological study. Environ Sci Pollut Res Int.26 (26), 27148 - 27167.
  • Yang S, Wang Y, Zhang Y et al. (2022). Oxidative stress and female infertility: mechanisms and management. Reprod Biol Endocrinol. 20, 65.
  • Zhang Y, Liu H, Wang L et al. (2021). Ethanol-induced oxidative stress and apoptosis in rat ovaries: involvement of mitochondrial dysfunction. Reprod Toxicol, 100, 56-65.
  • Zhou Y, Li X, Zhao C et al. (2022). Ethanol triggers excessive ROS generation and disrupts redox homeostasis in neuronal cells. Neurochem Res, 47, 2215–2228.
Toplam 35 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Veteriner Patoloji
Bölüm Araştırma Makalesi
Yazarlar

Gülşah Yıldız Deniz 0000-0001-7426-1754

Esra Laloğlu 0000-0001-5189-3564

Gönderilme Tarihi 5 Mayıs 2025
Kabul Tarihi 27 Ekim 2025
Erken Görünüm Tarihi 30 Kasım 2025
Yayımlanma Tarihi 30 Kasım 2025
Yayımlandığı Sayı Yıl 2025 Cilt: 36 Sayı: 3

Kaynak Göster

APA Yıldız Deniz, G., & Laloğlu, E. (2025). Modulatory Role of Hypericum perforatum on Oxidative Stress and Histopathological Changes in Ethanol-Exposed Rat Ovaries. Van Veterinary Journal, 36(3), 169-175. https://doi.org/10.36483/vanvetj.1691968
AMA Yıldız Deniz G, Laloğlu E. Modulatory Role of Hypericum perforatum on Oxidative Stress and Histopathological Changes in Ethanol-Exposed Rat Ovaries. Van Vet J. Kasım 2025;36(3):169-175. doi:10.36483/vanvetj.1691968
Chicago Yıldız Deniz, Gülşah, ve Esra Laloğlu. “Modulatory Role of Hypericum perforatum on Oxidative Stress and Histopathological Changes in Ethanol-Exposed Rat Ovaries”. Van Veterinary Journal 36, sy. 3 (Kasım 2025): 169-75. https://doi.org/10.36483/vanvetj.1691968.
EndNote Yıldız Deniz G, Laloğlu E (01 Kasım 2025) Modulatory Role of Hypericum perforatum on Oxidative Stress and Histopathological Changes in Ethanol-Exposed Rat Ovaries. Van Veterinary Journal 36 3 169–175.
IEEE G. Yıldız Deniz ve E. Laloğlu, “Modulatory Role of Hypericum perforatum on Oxidative Stress and Histopathological Changes in Ethanol-Exposed Rat Ovaries”, Van Vet J, c. 36, sy. 3, ss. 169–175, 2025, doi: 10.36483/vanvetj.1691968.
ISNAD Yıldız Deniz, Gülşah - Laloğlu, Esra. “Modulatory Role of Hypericum perforatum on Oxidative Stress and Histopathological Changes in Ethanol-Exposed Rat Ovaries”. Van Veterinary Journal 36/3 (Kasım2025), 169-175. https://doi.org/10.36483/vanvetj.1691968.
JAMA Yıldız Deniz G, Laloğlu E. Modulatory Role of Hypericum perforatum on Oxidative Stress and Histopathological Changes in Ethanol-Exposed Rat Ovaries. Van Vet J. 2025;36:169–175.
MLA Yıldız Deniz, Gülşah ve Esra Laloğlu. “Modulatory Role of Hypericum perforatum on Oxidative Stress and Histopathological Changes in Ethanol-Exposed Rat Ovaries”. Van Veterinary Journal, c. 36, sy. 3, 2025, ss. 169-75, doi:10.36483/vanvetj.1691968.
Vancouver Yıldız Deniz G, Laloğlu E. Modulatory Role of Hypericum perforatum on Oxidative Stress and Histopathological Changes in Ethanol-Exposed Rat Ovaries. Van Vet J. 2025;36(3):169-75.

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