DOI: 10.31196/huvfd.1958005 ISSN: 2146-717X

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

Halil Yavuz, Özge Kandemir, Hasan Şimşek, Nurhan Akaras, Fatih Mehmet Kandemir
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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.

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