Ratlarda klozapin kullanımı sonrası gelişen siyalore vemiyokardit üzerıne N-asetilsistein etkisinin histopatolojik vebiyokimyasal yöntemlerle incelenmesi
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Tarih
2023
Yazarlar
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Yayıncı
Necmettin Erbakan Üniversitesi Meram Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Amaç: Klozapinin ratlarda miyokard, parotis ve serum üzerindeki olumsuz etkilerinin hangi
mekanizmalar aracılığı ile olduğunun araştırılması, klozapin ile birlikte proflaktik N- asetil
sistein (NAS) kullanımı ile adı geçen yerlerde klozapine bağlı patolojik etkilerin ne düzeyde
olduğunun değerlendirilmesidir.
Gereç ve Yöntem: N.E.Ü. KONÜDAM Deneysel Tıp Uygulama ve Araştırma Merkezi’nden
temin edilen 350-400 gr ağırlığındaki 36 adet Wistar Albino ırkı ratlardan kontrol grubu,
klozapin grubu ve klozapin+NAS grubu olmak üzere üç grup oluşturuldu. 23 gün sonunda
ratlar dekapite edildi. Biyokimyasal olarak serumda Troponin I ve C Reaktif Protein (CRP);
serum, kalp ve parotiste Total Antioksidan Seviye (TAS), Total Oksidan Seviye (TOS),
Oksidatif Stres İndeksi (OSI), Tümör Nekroz Faktör Alfa (TNF-alfa) ve İnterlökin 10 (IL-10)
düzeyleri ile ve histopatolojik olarak parotis ve miyokard incelendi, istatiksel analiz yapıldı.
Bulgular: Ratlarda oluşturulan kontrol, klozapin ve klozapin+NAS grupları
karşılaştırıldığında kalp, parotis ve serumda CRP, Troponin, TNF-alfa, TOS, OSI
düzeylerinin en yüksek klozapin grubunda ve en düşük kontrol grubunda; IL-10 ve TAS
düzeylerinin en yüksek kontrol grubunda ve en düşük klozapin grubunda olduğu saptanmış
olup gruplar arasındaki farklılık istatiksel olarak da anlamlı bulunmuştur (p<0.05). Klozapine
NAS eklenen grupta ise tüm dokuların klozapin grubuna göre inflamasyon ve oksidasyon
açısından olumlu yönde etkilendiği görüldü. Kalp histopatolojik açıdan değerlendirildiğinde
yalnızca klozapin verilen grupta subendokardiyal ve miyokardiyal alanda lenfosit
infiltrasyonu, nükleer dejenerasyon, dejeneratif iskemik değişiklikler başta olmak üzere
inflamasyon bulguları daha yaygın gözlenirken klozapin+NAS grubunda daha az inflamasyon
gözlendi. Parotis histopatolojik açıdan değerlendirildiğinde yalnızca klozapin verilen grupta
periduktal, lobüler ve periglandüler alanda inflamasyon bulguları daha yaygın gözlenirken
klozapin+NAS grubunda daha az inflamasyon gözlendi. Klozapin verilen gruplarda parotiste
seröz komponentte müsinöz metaplazi tespit edildi.
Sonuç: Klozapinin ratlarda serum, parotis ve kalpte hem inflamatuar dengeyi hem de
antioksidan dengeyi olumsuz yönde etkilediği, NAS’ın bu olumsuz etkileri hem biyokimyasal
hem de histopatolojik yönden istatiksel yönden anlamlı olarak azalttığı sonucuna varıldı.
Objective: To investigate the mechanisms of the adverse effects of clozapine on myocardium, parotid gland and serum in rats and to evaluate the level of clozapine-induced pathologic effects of clozapine with prophylactic use of N-acetyl cysteine (NAS). Materials and Methods: Three groups including control group, clozapine group and clozapine+NAS group were formed from 36 Wistar Albino rats weighing 350-400 g obtained from N.E.Ü. KONÜDAM Experimental Medicine Application and Research Center. After 23 days, the rats were decapitated. Troponin I and C Reactive Protein (CRP) levels in serum; Total Antioxidant Level (TAS), Total Oxidant Level (TOS), Oxidative Stress Index (OSI), Tumor Necrosis Factor Alpha (TNF-alpha) and Interleukin 10 (IL-10) levels in serum, heart and parotid, and histopathologically parotid and heart were examined and statistical analysis was performed. Results: When the control, clozapine and clozapine+NAS groups were compared, it was found that CRP, Troponin, TNF-alpha, TOS, OSI levels in the heart, parotid and serum were highest in the clozapine group and lowest in the control group; IL-10 and TAS levels were highest in the control group and lowest in the clozapine group and the difference between the groups was statistically significant (p<0.05). In the group in which NAS was added to clozapine, all tissues were positively affected in terms of inflammation and oxidation compared to the clozapine group. When the heart was evaluated histopathologically, inflammation findings including lymphocyte infiltration, nuclear degeneration and degenerative ischemic changes in subendocardial and myocardial areas were observed more commonly in the clozapine-only group, while less inflammation was observed in the clozapine+NAS group. When parotid histopathologically evaluated, inflammation findings were observed more commonly in the periductal, lobular and periglandular areas in the clozapine only group, while less inflammation was observed in the clozapine+NAS group. Mucinous metaplasia was detected in the serous component of the parotid parotid in the clozapine groups. Conclusion: It was concluded that clozapine negatively affected both inflammatory balance and antioxidant balance in serum, parotid and heart of rats and NAS significantly reduced these negative effects both biochemically and histopathologically.
Objective: To investigate the mechanisms of the adverse effects of clozapine on myocardium, parotid gland and serum in rats and to evaluate the level of clozapine-induced pathologic effects of clozapine with prophylactic use of N-acetyl cysteine (NAS). Materials and Methods: Three groups including control group, clozapine group and clozapine+NAS group were formed from 36 Wistar Albino rats weighing 350-400 g obtained from N.E.Ü. KONÜDAM Experimental Medicine Application and Research Center. After 23 days, the rats were decapitated. Troponin I and C Reactive Protein (CRP) levels in serum; Total Antioxidant Level (TAS), Total Oxidant Level (TOS), Oxidative Stress Index (OSI), Tumor Necrosis Factor Alpha (TNF-alpha) and Interleukin 10 (IL-10) levels in serum, heart and parotid, and histopathologically parotid and heart were examined and statistical analysis was performed. Results: When the control, clozapine and clozapine+NAS groups were compared, it was found that CRP, Troponin, TNF-alpha, TOS, OSI levels in the heart, parotid and serum were highest in the clozapine group and lowest in the control group; IL-10 and TAS levels were highest in the control group and lowest in the clozapine group and the difference between the groups was statistically significant (p<0.05). In the group in which NAS was added to clozapine, all tissues were positively affected in terms of inflammation and oxidation compared to the clozapine group. When the heart was evaluated histopathologically, inflammation findings including lymphocyte infiltration, nuclear degeneration and degenerative ischemic changes in subendocardial and myocardial areas were observed more commonly in the clozapine-only group, while less inflammation was observed in the clozapine+NAS group. When parotid histopathologically evaluated, inflammation findings were observed more commonly in the periductal, lobular and periglandular areas in the clozapine only group, while less inflammation was observed in the clozapine+NAS group. Mucinous metaplasia was detected in the serous component of the parotid parotid in the clozapine groups. Conclusion: It was concluded that clozapine negatively affected both inflammatory balance and antioxidant balance in serum, parotid and heart of rats and NAS significantly reduced these negative effects both biochemically and histopathologically.
Açıklama
Anahtar Kelimeler
Klozapin, N asetil sistein, Miyokardit, Siyalore, Oksidasyon, Clozapine, N acetyl cysteine, Myocarditis, Sialorrhea, Oxidation
Kaynak
WoS Q Değeri
Scopus Q Değeri
Cilt
Sayı
Künye
Aksoy, Z. K. (2023). Ratlarda klozapin kullanımı sonrası gelişen siyalore vemiyokardit üzerıne N-asetilsistein etkisinin histopatolojik vebiyokimyasal yöntemlerle incelenmesi. (Yayınlanmamış tıpta uzmanlık tezi) Necmettin Erbakan Üniversitesi, Meram Tıp Fakültesi Dahili Tıp Bilimleri Bölümü Ruh Sağlığı ve Hastalıkları Anabilim Dalı, Konya.