Damla ÇETİN, PINAR AKSU KILIÇLE, Gülname Fındık GÜVENDİ, Muhammed YAYLA

Hepatoprotective Effect of Punica granatum Seed Oil Extract on Paracetamol Intoxication in Rat Via Inhibory Effect of CYP2E1

Punica granatum seed oil enriched by punikalagins has been shown to have a therapeutic effect against antidiabetic, anticancer, antiinflammatory and some organ toxicities. We aimed to reveal both protective and therapeutic effects of punica granatum seed oil, which has strong antioxidant and anti-inflammatory activity on paracetamol-induced hepatic toxicity via biochemically, molecularly and pathologically in our study. Our study, 64 albino wistar rats were fasted for 24 h and then divided into 8 equal groups. Group 1: Healthy, Group 2: 2 g/kg of paracetamol (2a: 24 h, 2b: 48 h) (orally), Group 3: 140 mg/kg of n-acetylcysteine (orally) + paracetamol, Group 4: 0.32 mg/mL Punica granatum (i.p) + paracetamol, Group 5: 0.64 mg/mL Punica granatum + paracetamol, Group 6: Paracetamol + 0.32 mg/mL Punica granatum, Group 7: Paracetamol + 0.64 mg/mL Punica granatum, Group 8: Paracetamol + 140 mg/kg n-acetylcysteine. The study was terminated at 24 and 48 h after paracetamol administration. Serum ALT and AST levels were significantly increased at 24th and 48th h of paracetamol administration according to toxicity. While malondialdehyde, CYP2E1 and TNF-α levels also increased in the liver, superoxide dismutase and glutathione peroxidase levels decreased significantly. Increased ALT, AST levels with malondialdehyde and TNF-α levels significantly decreased by punica granatum seed oil (low doses) application and antioxidant levels were also significantly improved. Punica granatum seed oil may be used as a potential therapeutic agent in the future by strengthening the antioxidant system and preventing inflammation, especially liver toxicity due to overdose of paracetamol in suicide- battered individuals.

Sıçanlarda CYP2E1 İnihibisyonu İle Parasetamol İntoksikasyonunda Punica granatum Çekirdek Yağı Ektraktının Hepatoprotektif Etkisi

Punikalaginlerle zengin olan Punica granatum çekirdek yağının, antidiyabetik, antikanser, antiinflamatuar ve bazı organ toksisitelerine karşı terepötik etkileri gösterilmiştir. Çalışmamızda, parasetamol ile indüklenen hepatotoksisite üzerine güçlü antioksidan ve anti-inflamatuvar etkinliğe sahip punica granatum çekirdek yağının biyokimyasal, moleküler ve patolojik olarak koruyucu ve terapötik etkilerini ortaya koymayı amaçladık. Çalışmamızda 64 albino wistar sıçan 24 saat aç bırakıldıktan sonra 8 eşit gruba ayrıldı. Grup 1: Sağlıklı, Grup 2: Parasetamol (2a: 24 saat, 2b: 48 saat) (oral), Grup 3: 140 mg/kg n-asetilsistein (oral) + parasetamol, Grup 4: 0.32 mg/mL Punica granatum (i.p.) + parasetamol, Grup 5: 0.64 mg/mL Punica granatum + parasetamol, Grup 6: Parasetamol + 0.32 mg/mL Punica granatum, Grup 7: Parasetamol + 0.64 mg/mL Punica granatum, Grup 8: Parasetamol + 140 mg/kg n-asetilsistein. Çalışma, parasetamol uygulamasından 24 ve 48 saat sonra sonlandırıldı. Parasetamol uygulamasının 24. ve 48. saatlerinde toksisiteye göre serum ALT ve AST düzeyleri anlamlı şekilde arttı. Malondialdehit, CYP2E1 ve TNF-α düzeyleri karaciğerde de yükselirken, süperoksit dismutaz ve glutatyon peroksidaz düzeyleri anlamlı olarak azaldı. Punica granatum çekirdek yağı (düşük dozlarda) uygulaması ile artmış ALT, AST düzeyleri, malondialdehit ve TNF-α seviyeleri anlamlı derecede azalmış ve antioksidan düzeyleri önemli derecede düzelmiştir. Punica granatum çekirdek yağı, intihar girişiminde bulunan kişilerde parasetamolün aşırı dozundan dolayı oluşan karaciğer toksisitesini önleyerek ve antioksidan sistemi güçlendirerek potansiyel terapötik bir madde olarak kullanılabilir

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