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Journals / Laboratuvar Hayvanları Bilimi ve Uygulamaları Dergisi / 2026 / Cilt: 6 Sayı: 2

Sodium Hydrosulfide Attenuates Vancomycin-Related Liver Damage in Rats: Roles of Redox Balance, Inflammation, and Cell Death

Sodyum Hidrosülfür, Sıçanlarda Vankomisin Kaynaklı Karaciğer Hasarını Azaltır: Redoks Dengesi, Enflamasyon ve Hücre Ölümünün Rolleri

Özlem Demir(Erzincan Binali Yıldırım Üniversitesi Tıp Fakültesi)0000-0001-9852-8839
Nurhan Akaras(AKSARAY ÜNİVERSİTESİ, TIP FAKÜLTESİ, TEMEL TIP BİLİMLERİ BÖLÜMÜ, HİSTOLOJİ VE EMBRİYOLOJİ ANABİLİM DALI)0000-0002-8457-9448
Pages
139–152
Publication Date
2026-09-23
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

In conclusion, NaHS protected against VAN-induced hepatotoxicity by reducing oxidative stress, inflammation, apoptosis, and oxidative DNA damage while preserving antioxidant defenses.

📌 3 Key Takeaways

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Objective & Hypothesis:Vancomycin (VAN), a glycopeptide antibiotic used to treat severe Gram-positive infections, may cause hepatotoxicity at high systemic exposure, limiting its clinical use.
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Key Findings & Data:Thirty adult male Sprague–Dawley rats were randomly assigned to five groups (n = 6): Control, NaHS (56 µmol/kg), VAN (200 mg/kg), VAN + NaHS28 (28 µmol/kg), and VAN + NaHS56 (56 µmol/kg).
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Conclusion & Impact:In conclusion, NaHS protected against VAN-induced hepatotoxicity by reducing oxidative stress, inflammation, apoptosis, and oxidative DNA damage while preserving antioxidant defenses.
🔬Design:Araştırma Makalesi
📍Scope:Comprehensive Sample
⚙️Variables:Karaciğer · Oksidatif stres · Sodyum hidrosülfür

Abstract

Vancomycin (VAN), a glycopeptide antibiotic used to treat severe Gram-positive infections, may cause hepatotoxicity at high systemic exposure, limiting its clinical use. Sodium hydrosulfide (NaHS), a water-soluble hydrogen sulfide (H₂S) donor, possesses antioxidant, anti-inflammatory, anti-apoptotic, and cytoprotective properties. This study investigated the hepatoprotective effects of NaHS against VAN-induced liver injury in rats. Thirty adult male Sprague–Dawley rats were randomly assigned to five groups (n = 6): Control, NaHS (56 µmol/kg), VAN (200 mg/kg), VAN + NaHS28 (28 µmol/kg), and VAN + NaHS56 (56 µmol/kg). Hepatic injury was evaluated by serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Oxidative stress was assessed by hepatic malondialdehyde (MDA), glutathione (GSH), and the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Inflammation, apoptosis, autophagy, and oxidative DNA damage were evaluated by measuring nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), caspase-3, beclin-1, and 8-hydroxy-2′-deoxyguanosine (8-OHdG), respectively. Histopathological examination was also performed. VAN significantly increased serum ALT and AST activities and hepatic MDA, NF-κB, TNF-α, caspase-3, beclin-1, and 8-OHdG levels, while reducing GSH content and GPx, SOD, and CAT activities (p < .001). NaHS treatment significantly attenuated these biochemical and histopathological alterations at both doses. In conclusion, NaHS protected against VAN-induced hepatotoxicity by reducing oxidative stress, inflammation, apoptosis, and oxidative DNA damage while preserving antioxidant defenses. These findings suggest that H₂S donors such as NaHS may represent promising therapeutic agents for preventing vancomycin-induced liver injury.

Özet

Vankomisin (VAN), şiddetli Gram-pozitif enfeksiyonların tedavisinde yaygın olarak tercih edilen bir glikopeptid antibiyotiktir. Ancak yüksek sistemik maruziyet, hepatotoksisiteye yol açarak ilacın klinik kullanımını sınırlandırabilmektedir. Hidrojen sülfürün (H₂S) suda çözünebilen bir donörü olan sodyum hidrosülfür (NaHS), güçlü antioksidan, anti-inflamatuvar, anti-apoptotik ve sitoprotektif özelliklere sahiptir. Bu çalışmada, NaHS'nin sıçanlarda VAN kaynaklı karaciğer hasarına karşı olası hepatoprotektif etkileri araştırılmıştır. Çalışmada otuz erişkin erkek Sprague–Dawley sıçan rastgele beş gruba ayrılmıştır (n = 6): Kontrol, NaHS (56 µmol/kg), VAN (200 mg/kg), VAN + NaHS28 (28 µmol/kg) ve VAN + NaHS56 (56 µmol/kg). Vankomisin yedi gün boyunca günde bir kez intraperitoneal olarak uygulanmış, NaHS ise her VAN uygulamasından 30 dakika sonra enjekte edilmiştir. Karaciğer hasarı, serum alanin aminotransferaz (ALT) ve aspartat aminotransferaz (AST) aktiviteleri ölçülerek değerlendirilmiştir. Oksidatif stres; karaciğer dokusunda malondialdehit (MDA) düzeyi ile birlikte glutatyon (GSH) içeriği ve antioksidan enzimler olan süperoksit dismutaz (SOD), katalaz (KAT) ve glutatyon peroksidaz (GPx) aktiviteleri belirlenerek değerlendirilmiştir. İnflamatuvar yanıt, nükleer faktör-kappa B (NF-κB) ve tümör nekroz faktörü-alfa (TNF-α) düzeyleri ile incelenirken; apoptoz, otofaji ve oksidatif DNA hasarı sırasıyla kaspaz-3, beklin-1 ve 8-hidroksi-2′-deoksiguanozin (8-OHdG) belirteçleri kullanılarak değerlendirilmiştir. Histopatolojik değişiklikler hematoksilen-eozin ile boyanmış karaciğer kesitlerinde incelenmiştir. Vankomisin uygulaması, serum ALT ve AST aktiviteleri ile karaciğer dokusunda MDA, NF-κB, TNF-α, kaspaz-3, beklin-1 ve 8-OHdG düzeylerini anlamlı düzeyde artırırken; GSH içeriği ile GPx, SOD ve KAT aktivitelerini belirgin şekilde azaltmıştır (p <0,001). NaHS uygulaması, her iki dozda da VAN'ın neden olduğu biyokimyasal ve histopatolojik değişiklikleri anlamlı ölçüde azaltmıştır (p <0,001). Histopatolojik bulgular biyokimyasal sonuçları desteklemiştir. Sonuç olarak NaHS, oksidatif stresi, inflamasyonu, apoptozu, otofajiyi ve oksidatif DNA hasarını baskılayarak, aynı zamanda karaciğerin antioksidan savunma sistemini koruyarak vankomisine bağlı hepatotoksisiteyi doza bağımlı şekilde hafifletmiştir. Bu bulgular, NaHS gibi H₂S donörlerinin vankomisine bağlı karaciğer hasarının önlenmesinde umut verici terapötik adaylar olabileceğini göstermektedir.

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Cite This Article

Demir, Ö., Akaras, N. (2026). Sodium Hydrosulfide Attenuates Vancomycin-Related Liver Damage in Rats: Roles of Redox Balance, Inflammation, and Cell Death. Laboratuvar Hayvanları Bilimi ve Uygulamaları Dergisi, Cilt: 6 Sayı: 2, 139–152. https://doi.org/10.62425/jlasp.1986492

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