Evaluation of the Protective Effects of Arbutin Via Hormonal, Anti-Inflammatory, and Antioxidant Pathways in Experimental Sepsis Induced Ovarian Damage

Abstract

The present study evaluated the dose-dependent protective effects of arbutin against sepsis-induced ovarian damage and to compare its prophylactic and post-sepsis adjuvant administration in rats. Forty-nine female Wistar albino rats were randomly assigned to seven groups (n=7): Control, Sham, pre-sepsis arbutin 50 mg/kg (Pre50), pre-sepsis arbutin 100 mg/kg (Pre100), Sepsis (SPS), post-sepsis arbutin 50 mg/kg (Post50), and post-sepsis arbutin 100 mg/kg (Post100). Sepsis was induced via cecal puncture. All sepsis groups received intramuscular amikacin (20 mg/kg/day) for five consecutive days. Arbutin was administered orally for seven days prior to sepsis (prophylactic protocol) or concurrently with antibiotics (post-sepsis protocol). Serum anti-Müllerian hormone (AMH) and estradiol (E2) levels were measured, and ovarian tissue concentrations of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), malondialdehyde (MDA), and glutathione (GSH) were determined. Sepsis significantly decreased serum AMH, E2, and ovarian GSH levels, while markedly increasing TNF-α, IL-6, and MDA concentrations. In arbutin-treated groups, both prophylactic and post-sepsis administration increased GSH and reduced TNF-α, IL-6, and MDA levels compared with the sepsis group. Although hormonal parameters improved partially, AMH and E2 did not return to control values within the experimental period.  Protective effects were similar across both doses 50 and 100 mg/kg, suggesting a dose-independent response. In conclusion, arbutin alleviated sepsis-induced inflammatory and oxidative ovarian damage through antioxidant and anti-inflammatory mechanisms; however, complete endocrine recovery was not achieved.

Keywords

• Arbutin
• inflammation
• ovarian damage
• oxidative stress
• sepsis

Supporting Institution

None

Project Number

None

Ethical Statement

All animal experiments were designed in accordance with the reporting and implementation principles defined in the ARRIVE guidelines and conducted in compliance with the European Union Directive 2010/63/EU on the protection of animals used for scientific purposes. All experimental procedures were reviewed and approved in advance by the Hatay Mustafa Kemal University Local Animal Ethics Committee, Hatay, Türkiye (2026/02-12).

Thanks

We would like to thank the students of Hatay Mustafa Kemal University Faculty of Veterinary Medicine for their generous assistance during the experimental study.

Deneysel sepsis kaynaklı ovaryum hasarında arbutinin hormonal, anti-inflamatuar ve antioksidan yollarla gösterdiği koruyucu etkilerinin değerlendirilmesi

Abstract

Bu çalışmada, sıçanlarda arbutinin sepsis ile indüklenen ovaryum hasarına karşı koruyucu etkilerinin doz bağımlı olarak değerlendirilmesi ve profilaktik uygulama ile sepsis sonrası adjuvan uygulamanın etkinliğinin karşılaştırılması amaçlandı. Toplam kırk dokuz dişi Wistar albino sıçan, yedi deney grubuna (her grupta n = 7) rastgele dağıtıldı: Kontrol, Sham, Sepsis (SPS), sepsis öncesi arbutin 50 mg/kg (Pre50), sepsis öncesi arbutin 100 mg/kg (Pre100), sepsis sonrası arbutin 50 mg/kg (Post50) ve sepsis sonrası arbutin 100 mg/kg (Post100). Deneysel sepsis, çekum ponksiyonu ile oluşturuldu. Sepsis oluşturulan tüm gruplara beş gün boyunca kas içi amikasin (20 mg/kg/gün) uygulandı. Arbutin, sepsis indüksiyonundan 7 gün önce (profilaktik protokol) veya antibiyotik tedavisiyle eş zamanlı olarak (sepsis sonrası protokol) oral yolla uygulandı. Deneyin sonunda, serum anti-Müllerian hormon (AMH) ve estradiol (E2) düzeyleri ölçüldü ve ovaryum dokusundan tümör nekroz faktörü-α (TNF-α), interlökin-6 (IL-6), malondialdehit (MDA) ve glutatyon (GSH) konsantrasyonları belirlendi. Deneysel sepsis, serum AMH ve E2 düzeylerinde ve ovaryum GSH konsantrasyonlarında önemli düşüşlere neden olurken, TNF-α, IL-6 ve MDA düzeylerinde belirgin artışlara yol açtı. Arbutin ile tedavi edilen gruplarda, hem profilaktik hem de sepsis sonrası uygulama, sepsis grubuna kıyasla GSH düzeylerinde artışa ve TNF-α, IL-6 ve MDA konsantrasyonlarında azalmaya neden oldu. Ancak, hormonal parametrelerde kısmi iyileşme görülmesine rağmen, AMH ve E2 seviyeleri deney süresi içinde kontrol değerlerine tam olarak geri dönmedi. Hem 50 hem de 100 mg/kg dozlarında benzer koruyucu etkiler gözlemlendi ve bu da büyük ölçüde dozdan bağımsız bir yanıtı gösterdi. Sonuç olarak, arbutin uygulaması, antioksidan ve anti-inflamatuar mekanizmalar yoluyla sepsis kaynaklı inflamatuar ve oksidatif yumurtalık hasarını iyileştirdi. Bununla birlikte, mevcut deney koşulları altında tam endokrin iyileşme sağlanamadı.

Keywords

• Arbutin
• inflamasyon
• ovaryum hasarı
• oksidatif stres
• sepsis

Supporting Institution

Hiçbiri.

Project Number

None

Ethical Statement

All animal experiments were designed in accordance with the reporting and implementation principles defined in the ARRIVE guidelines and conducted in compliance with the European Union Directive 2010/63/EU on the protection of animals used for scientific purposes. 428 Tüm hayvan deneyleri, ARRIVE kılavuzlarında tanımlanan raporlama ve uygulama ilkelerine uygun olarak tasarlanmış ve bilimsel amaçlarla kullanılan hayvanların korunmasına ilişkin Avrupa Birliği Direktifi 2010/63/AB'ye uygun olarak yürütülmüştür. Tüm deneysel prosedürler, Hatay Mustafa Kemal Üniversitesi Yerel Hayvan Etiği Kurulu (Hatay, Türkiye) tarafından önceden incelenmiş ve onaylanmıştır (2026/02-12).

Thanks

Deneysel çalışma süresince gösterdikleri cömert yardımlarından dolayı Hatay Mustafa Kemal Üniversitesi Veterinerlik Fakültesi öğrencilerine teşekkür ederiz.

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