PCOS'TA NİKOTİNAMİD MONONÜKLEOTİDİNİN HEPATOPROTEKTİF ROLÜ: SIÇAN MODELİNDEN HİSTOPATOLOJİK VE BİYOKİMYASAL KANITLAR

Öz

Amaç: Bu çalışmanın amacı, sıçan modelinde polikistik over sendromu (PCOS) ile ilişkili karaciğer hasarı üzerinde nikotinamid mononükleotid (NMN) 'nin histopatolojik ve biyokimyasal etkilerini araştırmaktı. Yöntem: Sıçanlarda deneysel olarak PCOS indüklendikten sonra, hayvanlar rastgele üç gruba ayrıldı: kontrol, PCOS ve NMN ile tedavi edilen PCOS. NMN, on yedi gün boyunca 500 mg/kg/gün dozunda intraperitoneally olarak uygulandı. Karaciğer dokuları histolojik analizler için toplandı. Genel hepatik mimari ve fibrotik değişiklikler sırasıyla hematoksilen-eozin ve Masson trikrom boyama kullanılarak değerlendirildi. Karaciğer fonksiyonunun göstergeleri olarak aspartat aminotransferaz (AST), alanin aminotransferaz (ALT) ve alkalin fosfataz (ALP) enzim aktiviteleri ölçüldü. Bulgular: Histopatolojik analiz, PCOS grubunda hepatosellüler balonlaşma, steatoz, lekelenmiş nekroz, portal ve lobüler inflamasyon, sinüzoidal dilatasyon, artmış apoptotik hepatositler ve artmış kollajen birikimi dahil olmak üzere önemli karaciğer hasarı olduğunu gösterdi. Yarı kantitatif puanlama, PCOS grubunda kontrollere kıyasla önemli ölçüde daha yüksek portal inflamasyon, balonlaşma dejenerasyonu, steatoz, lekelenmiş nekroz ve kapsüler inflamasyon puanları ortaya koydu. NMN tedavisi, inflamatuar infiltrasyonun azalması, lipit birikiminin azalması, apoptotik hücrelerin ve balonlaşma dejenerasyonunun zayıflaması ve kollajen lif birikiminin azalması ile kanıtlandığı üzere, bu histopatolojik değişiklikleri belirgin şekilde iyileştirdi. Buna göre, yarı kantitatif histopatolojik skorlar, PCOS+NMN grubunda PCOS grubuna göre anlamlı olarak daha düşüktü. Histolojik bulgularla tutarlı olarak, serum AST, ALT ve ALP aktiviteleri PCOS grubunda önemli ölçüde yükselmiş, ancak NMN uygulamasından sonra önemli ölçüde azalmıştır, bu da PCOS ile ilişkili karaciğer hasarında bir iyileşme olduğunu göstermektedir. Ayrıca NMN, PCOS ile ilişkili vücut ağırlığı artışını azaltmıştır. Sonuç: NMN tedavisi, karaciğer histopatolojisini iyileştirerek ve karaciğer enzim aktivitelerini normalleştirerek PCOS ile ilişkili karaciğer hasarını belirgin şekilde hafifletmiştir.

Anahtar Kelimeler

• Polikistik over sendromu
• DHEA
• Karaciğer
• Nikotinamid mononükleotid

HEPATOPROTECTIVE ROLE OF NICOTINAMIDE MONONUCLEOTIDE IN PCOS: HISTOPATHOLOGICAL AND BIOCHEMICAL EVIDENCE FROM A RAT MODEL

Öz

Objective: The objective of this study was to investigate the histopathological and biochemical effects of nicotinamide mononucleotide (NMN) on polycystic ovary syndrome (PCOS)-associated liver injury in a rat model. Methods: PCOS was experimentally induced in rats, after which the animals were randomly assigned to three groups: control, PCOS, and PCOS treated with NMN. NMN was administered intraperitoneally at a dose of 500 mg/kg/day for seventeen consecutive days. Liver tissues were collected for histological analyses. General hepatic architecture and fibrotic alterations were evaluated using hematoxylin–eosin and Masson’s trichrome staining, respectively. Enzyme activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were measured as indicators of liver function. Results: Histopathological analysis demonstrated significant hepatic damage in the PCOS group, including hepatocellular ballooning, steatosis, spotty necrosis, portal and lobular inflammation, sinusoidal dilatation, increased apoptotic hepatocytes, and enhanced collagen deposition. Semi-quantitative scoring revealed significantly higher portal inflammation, ballooning degeneration, steatosis, spotty necrosis, and capsular inflammation scores in the PCOS group compared with controls. NMN treatment markedly ameliorated these histopathological alterations, as evidenced by reduced histopathological damage. Accordingly, semi-quantitative histopathological scores were significantly lower in the PCOS+NMN group than in the PCOS group. Consistent with histological findings, serum AST, ALT, and ALP activities were significantly elevated in the PCOS group but were significantly reduced following NMN administration, indicating an improvement in PCOS-associated hepatic injury. Also, NMN significantly attenuated PCOS-associated body weight gain. Conclusion: NMN treatment markedly alleviated PCOS-associated liver injury by improving hepatic histopathology and normalizing liver enzyme activities

Anahtar Kelimeler

• Polycystic ovary syndrome
• DHEA
• Liver
• Nicotinamide mononucleotide

Kaynakça

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