Coenzyme Q10 as a protective and therapeutic agent against cisplatin-induced multi-organ toxicity in rats

Abstract

Aims: Cisplatin (CP) is a widely used chemotherapeutic agent whose dose-limiting toxicities are well documented. These toxicities are primarily mediated through oxidative stress, inflammation, and cellular injury. Coenzyme Q10 (CoQ10), a mitochondrial antioxidant and redox modulator, has shown promise in mitigating these toxic effects. The aim of this study was to evaluate the protective and therapeutic potential of CoQ10 against CP-induced multi-organ toxicity in rats. Methods: Male Sprague Dawley rats were divided into five (n=6 each) groups: control; CP; CoQ10; CoQ10 pre-treatment (PT); and CoQ10 pre-and post-treatment (PPT). CoQ10 was administered at 10 mg/kg/day intraperitoneally, based its antioxidant and cytoprotective efficacy. Biochemical markers of oxidative stress (malondialdehyde (MDA), nitric oxide (NO), 4-hydroxynonenal (4-HNE) and 8-hydroxydeoxyguanosine (8-OHdG)), antioxidant defences (reduced glutathione (GSH), catalase (CAT) and paraoxonase (PON)) and inflammation (adenosine deaminase (ADA)) were assessed in serum samples. Results: CP administration significantly increased oxidative and nitrosative stress markers, while suppressing endogenous antioxidants and elevating inflammatory mediators. CoQ10 treatment, particularly the PPT protocol, markedly restored antioxidant enzyme activities. This reduced lipid peroxidation and DNA oxidative lesions, while suppressing ADA activity. Notably, 8-OHdG levels decreased significantly, highlighting CoQ10’s role in preserving genomic integrity. Conclusion: CoQ10 exerts significant cytoprotective effects against CP-induced oxidative and inflammatory damage. PPT with CoQ10 was more effective than PT, emphasising the therapeutic value of pre-emptive antioxidant supplementation. These findings suggest that CoQ10 could be a beneficial addition to chemotherapy regimens involving CP.

Keywords

• CoQ10
• cisplatin
• oxidative stress
• antioxidant defense
• rat model

Sıçanlarda sisplatin kaynaklı çoklu organ toksisitesine karşı koruyucu ve terapötik ajan olarak koenzim Q10

Abstract

Amaç: Sisplatin (CP), doz sınırlayıcı toksisiteleri iyi belgelenmiş, yaygın olarak kullanılan bir kemoterapötik ajandır. Bu toksisiteleri öncelikle oksidatif stres, inflamasyon ve hücresel hasar aracılık eder. Mitokondriyal bir antioksidan ve redoks modülatörü olan koenzim Q10 (CoQ10), bu toksik etkileri hafifletmede umut verici sonuçlar göstermiştir. Bu çalışmanın amacı, sıçanlarda sisplatin kaynaklı çoklu organ toksisitesine karşı CoQ10'un koruyucu ve terapötik potansiyelini değerlendirmektir. Yöntemler: Erkek Sprague Dawley sıçanlar beş gruba (her biri n=6) ayrıldı: Kontrol; CP; CoQ10; CoQ10 ön tedavi (PT); ve CoQ10 ön ve son tedavi (PPT). CoQ10, antioksidan ve sitoprotektif etkinliğine göre 10 mg/kg/gün intraperitoneal olarak uygulandı. Oksidatif stresin biyokimyasal belirteçleri (malondialdehit (MDA), nitrik oksit (NO), 4-hidroksinonenal (4-HNE) ve 8-hidroksideoksiguanosin (8-OHdG)), antioksidan savunma (indirgenmiş glutatyon (GSH), katalaz (CAT) ve paraoksonaz (PON)) ve inflamasyon (adenozin deaminaz (ADA)) serum örneklerinde değerlendirildi. Sonuçlar: CP uygulaması, endojen antioksidanları baskılarken ve inflamatuar mediatörleri yükselterek oksidatif ve nitrozatif stres belirteçlerini önemli ölçüde artırdı. CoQ10 tedavisi, özellikle tedavi öncesi ve sonrası protokol, antioksidan enzim aktivitelerini belirgin şekilde geri kazandırdı. Bu, ADA aktivitesini baskılarken lipit peroksidasyonunu ve DNA oksidatif lezyonlarını azalttı. Özellikle, 8-OHdG düzeyleri önemli ölçüde azaldı, bu da CoQ10'un genomik bütünlüğü korumadaki rolünü vurguladı. Sonuç: CoQ10, CP'nin neden olduğu oksidatif ve inflamatuar hasara karşı önemli sitoprotektif etkiler gösterir. CoQ10 ile tedavi öncesi ve sonrası, tedavi öncesinden daha etkiliydi, bu da önleyici antioksidan takviyesinin terapötik değerini vurgulamaktadır. Bu bulgular, CoQ10'un sisplatin içeren kemoterapi rejimlerine faydalı bir katkı olabileceğini göstermektedir.

Keywords

• CoQ10
• sisplatin
• oksidatif stres
• antioksidan savunma
• sıçan modeli

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