Amoksisilin-klavulanik Asit Kaynaklı Karaciğer Hasarı Üzerine Karvakrolün Etkilerinin Araştırılması

Abstract

Çeşitli bakteriyel enfeksiyonların tedavisinde kullanılan amoksisilin-klavulanik asit (AMX), sıklıkla ilaca bağlı karaciğer hasarına neden olur, ancak bu hepatotoksik hasarın moleküler mekanizması henüz tam olarak aydınlatılmamıştır. Karvakrol (CRV), antioksidan ve antiinflamatuar özelliklerinin yanı sıra çeşitli farmakolojik özelliklere sahip doğal bir flavonoiddir. Bu çalışma, insan ve hayvan sağlığında sıklıkla kullanılan AMX'in neden olduğu karaciğer hasarına karşı CRV'nin koruyucu etkisini araştırmıştır. Yirmi sekiz Wistar albino sıçan dört gruba ayrılmıştır: kontrol, AMX, CRV ve AMX+CRV. AMX (30 mg/kg) ve CRV (50 mg/kg) yedi gün boyunca günde bir kez oral olarak uygulanmıştır. Karaciğer dokusu hasarını belirlemek için karaciğer fonksiyonu, oksidatif stres ve inflamasyon parametreleri analiz edilmiştir. Doku hasarını ve yapısal değişiklikleri tespit etmek için histopatolojik analiz yapılmıştır. AMX, karaciğer dokusunda Aspartat aminotransferaz (AST) ve Alanin aminotransferaz (ALT) seviyelerini artırmıştır. AMX'in ayrıca, lipid peroksidasyon belirteci olan malondialdehit (MDA) ve pro-apoptotik proteinler Kaspaz-3 ve Bax'ı artırdığı, glutatyon (GSH), glutatyon peroksidaz (GPx), süperoksit dismutaz (SOD) ve katalaz (CAT) enzim aktivitelerinin yanı sıra otofaji süreçlerinde kritik roller oynayan pro-apoptotik proteinler B hücreli lenfoma-2 (BCL-2), Beclin1 ve Mikrotübül ilişkili protein 1 hafif zincir 3A'yı (LC3A) azalttığı bulunmuştur. AMX'in ayrıca karaciğer iltihabı belirteçleri olan nükleer faktör kappa B (NF-κB), interlökin-17A (IL-17A) ve interlökin-1β'nın (IL-1β) ekspresyon seviyelerini artırdığı da tespit edilmiştir. CRV'nin AMX ile birlikte uygulanmasının AST, ALT, MDA, NF-κB, IL-17A, IL-1β, Caspase-3 ve Bax düzeylerini düşürdüğü, buna karşılık GSH düzeylerini, GPx, SOD, CAT aktivitelerini ve BCL-2'yi artırdığı belirlendi. Elde edilen bulgular birlikte değerlendirildiğinde, AMX'in karaciğer hasarına neden olduğu ve CRV ile destekleyici tedavinin bu karaciğer hasarını azalttığı tespit edildi.

Keywords

• Amoksisilin-klavulanik asit
• İnflamasyon
• Karaciğer
• Karvakrol
• oksidatif stres

Supporting Institution

Yok

Ethical Statement

Tüm deneysel prosedürler, Necmettin Erbakan Üniversitesi Hayvan Deneyleri ve Etik Komitesi tarafından resmi olarak onaylanmıştır (20.02.2025, 2025–012).

Thanks

yok

Investigation of The Effects of Carvacrol on Amoxicillin-Clavulanic Acid-Induced Liver Damage

Abstract

Amoxicillin-clavulanic acid (AMC) is frequently implicated in drug-induced hepatic damage during antimicrobial therapy; however, the molecular mechanisms driving this adverse event remain poorly understood. Carvacrol (CRV), a monoterpenic phenol, exhibits potent antioxidant and anti-inflammatory properties. This study aimed to investigate whether CRV exerts a hepatoprotective effect against AMC-induced liver injury. Male Wistar albino rats (n=28) were allocated into four groups: control, AMC (30 mg/kg), CRV (50 mg/kg), and AMC+CRV, administered via oral gavage daily for seven days. Hepatic damage was evaluated by assessing liver function markers, oxidative stress parameters, inflammatory pathways, autophagic markers, and histopathological alterations. AMC administration induced acute hepatic injury, significantly elevating serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. AMC also increased hepatic malondialdehyde (MDA) content, upregulated pro-apoptotic proteins (Caspase-3 and Bax), and elevated inflammatory markers [nuclear factor kappa B (NF-κB), interleukin-17A (IL-17A), and interleukin-1β (IL-1β)], alongside autophagic markers [Beclin-1 and Light chain 3A (LC3A)]. Conversely, AMC suppressed glutathione levels, reduced superoxide dismutase, catalase, and glutathione peroxidase activities, and downregulated the anti-apoptotic protein B-cell lymphoma-2 (BCL-2). Co-administration of CRV with AMC significantly attenuated AST, ALT, MDA, NF-κB, IL-17A, IL-1β, Caspase-3, Bax, Beclin-1, and LC3A levels, while successfully restoring antioxidant defenses and BCL-2 expression. Furthermore, CRV markedly ameliorated AMC-induced histopathological tissue damage. Collectively, these findings suggest that CRV exerts a protective effect against AMC-induced hepatotoxicity, associated with the attenuation of oxidative stress, apoptosis, autophagy, and inflammation.

Keywords

• Amoxicillin-clavulanic acid
• carvacrol
• inflammation
• liver
• oxidative stress

Supporting Institution

None

Ethical Statement

This study was approved by the Necmettin Erbakan University Animal Experiments Local Ethics Committee (20.02.2025, 2025/012 Number Ethics Committee Decision). In addition, the authors declared that Research and Publication Ethical rules were followed.

Thanks

none

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