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. 2013 Oct;45(3):167-75.
doi: 10.5152/eajm.2013.35.

The effects of erdosteine and N-acetylcysteine on apoptotic and antiapoptotic markers in pulmonary epithelial cells in sepsis

Rezan Demiralay  1 , Nesrin Gürsan  2 , Havva Erdem  2
Affiliations

The effects of erdosteine and N-acetylcysteine on apoptotic and antiapoptotic markers in pulmonary epithelial cells in sepsis

Rezan Demiralay et al. Eurasian J Med. 2013 Oct.

Abstract
in English, Turkish

Objective: This study investigated the frequency of apoptosis in rat pulmonary epithelial cells after the injection of an intraperitoneal endotoxin lipopolysaccharide (LPS), the effects of LPS on apoptotic (bax, caspase-3) and antiapoptotic (bcl-2) markers during lung damage, and the protective effects of two known antioxidant agents, erdosteine and N-acetylcysteine (NAC).

Materials and methods: Male Wistar rats were divided into the following six groups, which included nine rats each: two control groups, two LPS-treated groups, one erdosteine-treated group (150 mg/kg), and one NAC-treated group (150 mg/kg). LPS was injected intraperitoneally at a dosage of 20 mg/kg. Following LPS injection, the antioxidants were orally administered. The rats were sacrificed at 24 h after LPS administration. The levels of apoptosis in bronchiolar and alveolar cells were determined using the TUNEL-staining method. Immunohistochemical staining of cytoplasmic bax, caspase-3, and bcl-2 in the epithelial cells was performed.

Results: Erdosteine and NAC significantly reduced the rate of LPS-induced pulmonary epithelial cell apoptosis. The effect of NAC on regulating apoptosis was weaker than that of erdosteine. Erdosteine and NAC significantly reduced the local induction of bax and caspase 3 and significantly increased the reduced local production of bcl-2.

Conclusion: These findings suggest that erdosteine and NΑC can effectively protect the lungs from the damaging effects of LPS.

Amaç: Bu çalışma, sıçanlarda intraperitoneal endotoksin (LPS) uygulanmasından sonra pulmoner epitel hücrelerdeki apopitozis sıklığını, akciğer hasarında apopitotik ve antiapopitotik göstergeler (bax, kaspaz-3 ve bcl-2) üzerine LPS’in etkilerini ve bilinen iki antioksidan ilacın (erdostein ve asetilsistein) koruyucu etkilerini araştırmak amacıyla yapıldı.

Gereç ve yöntem: Sıçanlar, her biri 9 hayvandan oluşan 6 gruba ayrıldı. Bunlar; 2 negatif kontrol, 2 pozitif kontrol, erdostein (150mg/kg) ile tedavi edilen ve asetilsistein (150mg/kg) ile tedavi edilen gruplardı. Sıçanlara 20mg/kg vücut ağırlığı dozunda intraperitoneal olarak LPS solüsyonu enjekte edildi. LPS enjeksiyonunu takiben oral antioksidan ilaç tedavisine başlandı. Sıçanlar LPS uygulanmasından 24 saat sonra öldürüldü. Bronşiol ve alveol epitel hücrelerinde TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick endlabelling) yöntemi kullanılarak apopitozis düzeyi belirlendi. Epitel hücrelerindeki sitoplazmik bax, kaspaz-3 ve bcl-2 boyanması immünhistokimyasal olarak değerlendirildi.

Bulgular: Erdostein ve asetilsistein tedavisi, sepsisin neden olduğu pulmoner epitel hücre apopitozisi oranını istatistiksel olarak önemli ölçüde azalttı. Asetilsisteinin epitel hücre apopitozis regülasyonu üzerine etkisinin erdosteine göre daha zayıf olduğu bulundu. Erdostein ve asetilsistein, lokal bax ve kaspaz-3 oluşum seviyelerindeki artışı istatistiksel olarak önemli ölçüde azalttı ve lokal bcl-2 seviyesindeki azalışı önemli ölçüde artırdı.

Sonuç: Bu bulgular, Erdostein ve asetilsisteinin akciğerleri LPS’in zararlı etkilerinden korumada etkili olabileceğini göstermektedir.

Keywords: Apoptosis; N-acetylcysteine; epithelial cells; erdosteine; pathogenesis; sepsis.

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Figures

Figure 1.
Figure 1.
Photomicrographs of apoptotic cells (brown-stained nuclei) in the bronchiolar and alveolar epithelia as detected using the TUNEL method (original magnification, 200×). a: the negative control group; b: the LPS-treated group; c: the erdosteine-treated group; d: the NAC-treated group.
Figure 2.
Figure 2.
Photomicrographs of the bax analysis in the bronchiolar and alveolar epithelial cells, as detected by immunohistochemical staining (original magnification, 400×). a: the negative control group; b: the LPS-treated group; c: the erdosteine-treated group; d: the NAC-treated group.
Figure 3.
Figure 3.
Photomicrographs of the caspase 3 analysis in the bronchiolar and alveolar epithelial cells, as detected by immunohistochemical staining (original magnification, 400×). a: the negative control group; b: the LPS-treated group; c: the erdosteine-treated group; d: the NAC-treated group.
Figure 4.
Figure 4.
Photomicrographs of bcl-2 analysis in the bronchiolar and alveolar epithelial cells as detected by immunohistochemical staining (original magnification, 200×). a: negative control group; b: LPS-treated group; c: Erdosteine-treated group; d: NAC-treated group.
See this image and copyright information in PMC

References

    1. Freeman BD, Natanson C. Anti-inflammatory therapies in sepsis and septic shock. Expert Opin Investig Drugs. 2000;9:1651–63. - PubMed
    1. Ayala A, Lomas JL, Grutkoski PS, Chung CS. Pathological aspects of apoptosis in severe sepsis and shock? Int J Biochem Cell Biol. 2003;35:7–15. - PubMed
    1. Czermak BJ, Breckwoldt M, Ravage ZB, et al. Mechanisms of enhanced lung injury during sepsis. Am J Pathol. 1999;154:1057–65. - PMC - PubMed
    1. Ayala A, Lomas JL, Grutkoski PS, Chung S. Fas-ligand mediated apoptosis in severe sepsis and shock. Scand J Infect Dis. 2003;35:593–600. - PubMed
    1. Scaffidi C, Fulda S, Srinivasan A, et al. Two CD95 (APO-1/Fas) signaling pathways. EMBO J. 1998;17:1675–87. - PMC - PubMed