Ratlarda Gentamisin Kaynaklı Nefrotoksisiteye Karşı Cranberry’nin Koruyucu Etkisinin Değerlendirilmesi

Abstract

Gentamisin (GTC), yaygın olarak kullanılan bir aminoglikozid antibiyotiktir; ancak terapötik kullanımı, esas olarak oksidatif stres kaynaklı nefrotoksik ve hepatotoksik etkiler nedeniyle sınırlıdır. Bu çalışmada, antioksidan ve antiinflamatuvar özellikleriyle bilinen cranberry (CRB) (Vaccinium macrocarpon) ekstraktının, GTC’nin ratlarda oluşturduğu renal ve hepatik hasara karşı olası koruyucu rolü araştırılmıştır. Otuz iki rat kontrol, CRB, GTC + CRB ve GTC olmak üzere dört gruba ayrılmıştır. GTC (80 mg/kg, s.c.) ve CRB (200 mg/kg, p.o.) uygulamaları yedi ardışık gün boyunca yapılmıştır. Biyokimyasal analizlerde, GTC grubunda serum BUN, üre, kreatinin, ALT ve AST düzeylerinde anlamlı artışlar gözlenmiş ve bu durum renal ve hepatik fonksiyon bozukluğunu doğrulamıştır. CRB ile birlikte uygulama, bu artışları azaltmış ve antioksidan parametreleri iyileştirmiştir; bu iyileşme, MDA ve oksidatif stres indeksindeki azalma ile total ve native tiyol düzeylerindeki artışla (p < 0.001) kendini göstermiştir. Gen ekspresyon analizleri, GTC’nin pro-apoptotik genleri (Bax, kaspaz-3 ve kaspaz-9) artırdığını, anti-apoptotik Bcl-2 ekspresyonunu ise azalttığını göstermiştir; buna karşın CRB birlikte uygulaması bu değişiklikleri tersine çevirmiştir. Histopatolojik değerlendirmeler biyokimyasal bulguları desteklemiş, GTC grubunda belirgin tübüler ve hepatoselüler nekroz, inflamatuvar infiltrasyon ve hemoraji saptanmış, CRB uygulamasıyla bu bulguların belirgin şekilde hafiflediği gözlenmiştir. Sonuçlar, CRB’nin GTC’nin neden olduğu oksidatif ve apoptotik hasara karşı kısmi böbrek ve karaciğer koruyucu etki gösterebileceğini ve bu etkinin muhtemelen antioksidan ve sitoprotektif özelliklerinden kaynaklandığını düşündürmektedir.

Keywords

• Gentamisin
• Antioksidan
• Oksidadif stres
• Cranberry
• Nefrotoksisite

Evaluation of the Protective Effect of Cranberry in Gentamicin-Induced Nephrotoxicity in Rats

Abstract

Gentamicin (GTC) is a widely used aminoglycoside antibiotic, but its therapeutic application is limited by nephrotoxic and hepatotoxic effects primarily driven by oxidative stress. This study investigated the potential protective role of cranberry (CRB) (Vaccinium macrocarpon), known for its antioxidant and anti-inflammatory properties, against GTC-induced nephrotoxicity in rats. Hepatic biochemical and histopathological parameters were also evaluated as supportive markers of systemic toxicity. Thirty-two rats were divided into four groups: Control, CRB, GTC + CRB, and GTC. GTC (80 mg/kg, s.c.) and CRB (200 mg/kg, p.o.) were administered for seven consecutive days. Biochemical analyses showed significant increases in serum BUN, urea, creatinine, ALT, and AST levels in the GTC group, confirming renal and hepatic impairment. Co-treatment with CRB reduced these elevations and improved antioxidant parameters, reflected by decreased MDA and oxidative stress index levels and increased total and native thiols (p < 0.001). Gene expression analyses demonstrated that GTC upregulated pro-apoptotic genes (Bax, caspase-3, -9) and downregulated the anti-apoptotic Bcl-2, whereas CRB co-administration reversed these alterations. Histopathological evaluations supported the biochemical findings, revealing severe tubular and hepatocellular necrosis, inflammatory infiltration, and hemorrhage in the GTC group, which were markedly alleviated by CRB supplementation. These results suggest that CRB may exert a partial renoprotective effect against GTC-induced oxidative and apoptotic damage, possibly through its antioxidant and cytoprotective properties.

Keywords

• Antioxidant
• Cranberry
• Gentamicin
• Nephrotoxicity
• Oxidative stress

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