Leflunomide Improves Lipid Profiles and Oxidative Stress in the Hypothalamus of Acute High-Fructose-Fed Rats

Abstract

This study aimed to investigate the effects of oxidative stress and lipid profiles on the hypothalamus of rats fed with acute high-dose fructose and the possible contribution of leflunomide to these effects. Totally 48 Spraque–Dawley male rats 12-16 weeks old, weighing 250-300 g were included and were randomly divided into 6 groups; group 1: control, group 2: carboxymethyl cellulose+control, group 3: leflunomide, group 4: acute high-dose fructose, group 5: acute highdose fruct ose+c arbox ymeth yl cellulose, and group 6: acute high-dose fruct ose+l eflun omide. Acute high-dose fructose groups were given 63% fructose solution for 24 hours after 48 hours of fasting. Since leflunomide is not soluble in water, it was dissolved in 1% carboxymethyl cellulose solution and 10 mg/kg/day of leflunomide was administered orally in the morning and evening. After 72 hours, the rats were sacrificed under general anesthesia and the hypothalamus tissue was removed. The low-density lipoprotein (LDL), total cholesterol, total antioxidant-oxidant status (TAS-TOS), and oxidative stress index (OSI) levels were determined from the obtained hypothalamus tissue using commercial kits based on enzyme-linked immunosorbent assay method. There was no significant difference between the groups in total antioxidant level. A significant increase was found in the TOS and OSI levels in fourth group vs first group (P < 0.001). In the treatment groups, a statistically significant decrease was observed with leflunomide (P < .05). A statistically significant decrease was detected in LDL and total cholesterol levels in sixth group versus fourth group (P < .05). In this study, the importance of Leflunomide in reducing oxidative stress and lipid profile in high fructose-fed rats was determined. In conclusion, Leflunomide may be promising in reducing brain damage due to oxidative stress.

Keywords

• Fruktoz
• LDL
• leflunomid
• oksidatif stres
• total kolesterol

Leflunomid Akut Yüksek Fruktoz ile Beslenen Sıçanların Hipotalamusunda Lipid Profillerini ve Oksidatif Stresi İyileştirir

Öz

Bu çalışmada, akut yüksek doz fruktozla beslenen sıçanlarda oksidatif stres ve lipid profillerinin sıçan hipotalamusu üzerine etkileri ve bu etkilerinde Leflunomid’in olası katkısının incelenmesi amaçlanmıştır. Çalışmaya 12-16 haftalık, 250-300 g ağırlığındaki 48 Spraque Dawley erkek sıçanlar dahil edilmiş ve rastgele 6 gruba ayrılmıştır. (Grup 1 (Kontrol); Grup 2 karboksimetil selülöz (CMC)+kontrol; Grup 3 (Leflunomid), Grup 4 (Akut yüksek doz fruktoz), Grup 5 (Akut yüksek doz fruktoz + CMC), Grup 6 (Akut yüksek doz fruktoz + Leflunomid). Akut yüksek doz fruktoz grupları sıçanların 48 saat açlığı takiben 24 saat boyunca %63’lük fruktoz çözeltisi ile beslenmeleri sağlanarak oluşturulmuştur. Leflunomid ise suda çözünmediği için %1’lik CMC çözeltisi içinde çözülmüştür ve 10 mg/kg/gün Leflunomid sabah akşam oral yolla uygulanmıştır. 72 saatin sonunda sıçanlar genel anestezi altında sakrifiye edilmiş ve hipotalamus dokusu çıkarılmıştır. Elde edilen hipotalamus dokusundan düşük yoğunluklu lipoprotein (LDL), total kolesterol, total antioksidan-oksidan (TAS-TOS), oksidatif stres indeksi (OSİ) düzeyleri solid faz sandwich (ELİSA) prensibine dayanan hazır ölçüm kitleri kullanılarak belirlenmiştir. TAS düzeyinde gruplar arasında anlamlı fark saptanmamıştır. TOS ve OSİ düzeylerinde, 4. grupta 1. gruba göre anlamlı artış tespit edilmiştir (P < ,001). Tedavi gruplarına bakıldığında leflunomid uygulanan gruplarda istatistiksel olarak anlamlı azalma görülmüştür (P < ,05). LDL ve total kolesterol düzeylerinde ise 6. grupta 4. gruba göre istatistiksel olarak anlamlı düzeyde azalma tespit edilmiştir (P < ,05). Bu çalışmada, yüksek fruktozla beslenen sıçanlarda, oksidatif stresin ve lipit profilinin azalmasında Leflunomid’in önemi belirlenmiştir. Sonuç olarak, Leflunomid oksidatif strese bağlı gelişen beyin hasarının azalmasında umut vaat edici olabilir.

Anahtar Kelimeler

• Fruktoz
• LDL
• leflunomid
• oksidatif stres
• total kolesterol

Kaynakça

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