Antifibrotic effects of Berberine and N-acetylcysteine in a rat model of diabetic lung fibrosis

Öz

Objective: Diabetes mellitus (DM) is a metabolic condition characterized by chronically high blood glucose concentrations. DM affects many organs, including the liver, kidneys, and brain, and its association with lung damage, as manifested by pulmonary fibrosis, has been established. Chronic high blood sugar can also cause structural damage to the lungs, a condition known as diabetic lung fibrosis. Berberine (BBR) and N-acetylcysteine (NAC) exert a wide range of biological activities, including antioxidant, anti-inflammatory, and antifibrotic actions. The primary purpose of this research is to investigate the therapeutic potential of Berberine (BBR) and N-acetylcysteine (NAC) in the progression of lung fibrosis in rats with induced diabetes. Methods: Thirty rats were included in the experiment and allocated into five groups (n = 6): a control; a diabetes (D) receiving streptozotocin (STZ, 45 mg/kg); a D+BBR group treated with STZ (45 mg/kg) and berberine (50 mg/kg/day); a D+NAC group administered STZ (45 mg/kg) and N-acetylcysteine (50 mg/kg/day); and a combined treatment group (D+NAC+BBR) given STZ (45 mg/kg) followed by NAC (50 mg/kg/day) and BBR (50 mg/kg/day). Lung tissues were evaluated by histopathological and immunohistochemical techniques. Results: TGF-β1 and collagen expression significantly increased in group D (27,66) compared to the control group (2,16) (p<0.001). TGF-β1 expression was significantly reduced in both combined (9,83) and the individual treatment groups of D+BBR (17,51) (p<0.01) and D+NAC (11,16) (p<0.001). Similarly, both individual (p<0.01) and combined (9,51) (p<0.001) treatments of BBR (11,51) and NAC (13,33) significantly decreased collagen expression (p<0.05). Additionally, alveolar thickening and dense collagen deposition were observed in group D. These pathological changes were reduced with both combined and the individual treatments of BBR and NAC. Conclusion: The results indicate that diabetes mellitus induces marked pathological alterations, including alveolar wall thickening, dense collagen deposition, and a significant upregulation of the pro-fibrotic cytokine TGF-β1. Based on the experimental findings, this study demonstrates that BBR and NAC possess significant antifibrotic properties in a rat model of diabetic lung fibrosis.

Anahtar Kelimeler

• Berberine
• Diabetes mellitus
• N-acetylcysteine
• Pulmonary fibrosis
• Rat

Berberin ve N-asetilsisteinin diyabetik akciğer fibrozisi sıçan modelinde antifibrotik etkileri

Öz

Amaç: Diyabet mellitus (DM), kronik olarak yüksek kan şekeri konsantrasyonları ile karakterize edilen metabolik bir durumdur. DM, karaciğer, böbrekler ve beyin de dahil olmak üzere birçok organı etkiler ve akciğer fibrozisi ile kendini gösteren akciğer hasarıyla ilişkisi kanıtlanmıştır. Kronik yüksek kan şekeri ayrıca akciğerlerde yapısal hasara da neden olabilir; bu durum diyabetik akciğer fibrozisi olarak bilinir. Berberin (BBR) ve N-asetilsistein (NAC), antioksidan, antiinflamatuar ve antifibrotik etkiler de dahil olmak üzere geniş bir yelpazede biyolojik aktivite gösterir. Bu araştırmanın temel amacı, indüklenmiş diyabetli sıçanlarda akciğer fibrozisinin ilerlemesinde Berberin (BBR) ve N-asetilsisteinin (NAC) terapötik potansiyelini araştırmaktır. Yöntemler: Deneyde otuz sıçan kullanıldı ve beş gruba ayrıldı (n = 6): bir kontrol grubu; tek doz streptozotosin (STZ, 45 mg/kg) alan bir diyabet (D) grubu; STZ (45 mg/kg) ve berberin (50 mg/kg/gün) ile tedavi edilen bir D+BBR grubu; STZ (45 mg/kg) ve N-asetilsistein (50 mg/kg/gün) uygulanan bir D+NAC grubu; ve STZ (45 mg/kg) ardından NAC (28 gün boyunca 50 mg/kg/gün) ve BBR (50 mg/kg/gün) verilen kombine bir tedavi grubu (D+NAC+BBR). Akciğer dokuları histopatolojik veimmünohistokimyasal tekniklerle değerlendirildi.. Bulgular: D grubunda (27,66) kontrol grubuna (2,16) kıyasla TGF-β1 ve kollajen ekspresyonu anlamlı derecede artmıştır (p<0.001). TGF-β1 ekspresyonu, hem kombine (9,83) hem de D+BBR (17,51) (p<0.01) ve D+NAC (11,16) (p<0.001) gruplarının bireysel tedavilerinde anlamlı derecede azalmıştır. Benzer şekilde, BBR (11,51) ve NAC (13,33)'nin hem bireysel (p<0.01) hem de kombine (9,51) (p<0.001) tedavileri kollajen ekspresyonunu anlamlı derecede azaltmıştır (p<0.05). Ek olarak, D grubunda alveol kalınlaşması ve yoğun kollajen birikimi gözlemlenmiştir. Bu patolojik değişiklikler, BBR ve NAC'nin hem kombine hem de bireysel tedavileriyle azalmıştır. Sonuç: Sonuçlar, diyabetin alveol duvarı kalınlaşması, yoğun kolajen birikimi ve pro-fibrotik sitokin TGF-β1'in önemli ölçüde artışı da dahil olmak üzere belirgin patolojik değişikliklere neden olduğunu göstermektedir. Deneysel bulgulara dayanarak, bu çalışma BBR ve NAC'nin diyabetik akciğer fibrozisi sıçan modelinde önemli antifibrotik özelliklere sahip olduğunu göstermektedir.

Anahtar Kelimeler

• Berberin
• Diyabetes mellitus
• N-asetilsistein
• Pulmoner fibroz
• Sıçan

Kaynakça

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