Candida Albicans ile infekte edilmiş farelerde amfoterisin B tedavisinin tedavisinin kronoterapi yönünden incelenmesi

Abstract

CANDIDA ALBICANS İLE İNFEKTE EDİLMİŞ FARELERDE AMFOTERİSİN B TEDAVİSİNİN KRONOTERAPİ YÖNÜNDEN İNCELENMESİ Çalışmamızda Candida infeksiyonu oluşturulan deney model farelerde kronobiyolojiden yararlanarak AmB tedavisinin böbrek infeksiyonu ve patogenezi üzerine etkisini araştırmayı amaçladık. Çalışmamızda kullanılan 32 deney ve 7 kontrol faresi klinik C. albicans suşu (8 log kob/ ml) ile infekte edilerek 6 gruba ayrılmıştır. İnfeksiyondan 24 saat sonra 1. grup kontrol farelerine 0800’ de FTS (0.2 ml/ gün/ ip), 2. grup kontrol farelerine 1800’ de FTS (0.2 ml/ gün/ ip), 3. grup farelere 0800’ de AmB (1 mg/ kg/ gün/ ip), 4. grup farelere 1800’ de AmB (1 mg/ kg/ gün/ ip), 5. grup farelere 0800’ de AmB (0.5 mg/ kg/ gün/ ip), 6. grup farelere 1800’ de AmB (0.5 mg/ kg/ gün/ ip) 3 gün süre ile uygulanmıştır. AmB’nin böbrek toksisitesinin kronoterapi ile değerlendirilmesinde 10 sağlıklı deney ve 4 sağlıklı kontrol faresi kullanılmıştır. 1. kontrol grubuna 0800’ de FTS (0.2 ml/ gün/ ip), 2. kontrol grubuna 1800’ de FTS (0.2 ml//gün/ ip), 3. grubuna 0800’ de AmB (5 mg/ kg/ gün/ ip), 4. grubuna 1800’ de AmB (5 mg/ kg/ gün/ ip) 4 gün süre ile uygulanmıştır. 1800’ de AmB (0.5 mg/ kg/ gün/ ip) tedavisi uygulanan deney farelerinin böbreklerindeki Candida sayısı, 0800 grubuna göre anlamlı olarak azalmıştır (p<0.05). AmB (1 mg/ kg/ gün/ ip) tedavisi uygulanan 0800 ve 1800 grupları arasında anlamlı bir fark saptanmamıştır (p>0.05). AmB (1 mg/ kg/ gün/ ip) tedavisi uygulanan 1800 grubunda histopatolojik bulgular 0800 grubuna göre anlamlı olarak azalmıştır (p<0.05). Yüksek doz AmB (5 mg/ kg/ gün/ ip) uygulanan 1800 grubu deney farelerinin serum BUN ve serum kreatinin seviyesi 0800 grubuna göre anlamlı olarak azalmıştır (p<0.05). Yüksek doz AmB (5 mg/ kg/ gün/ ip) tedavisi uygulanan 1800 grubunda histopatolojik bulgular 0800 grubuna göre anlamlı olarak azalmıştır. Çalışmamızda 1800’de, düşük terapötik dozda AmB (0.5 mg/ kg/ gün/ ip) tedavisinin infeksiyonu azalttığı mikrobiyolojik yöntemlerle, 1800 de yüksek doz AmB (5 mg/ kg/ gün/ ip) uygulamasının ise 0800’ de uygulanan gruba göre böbreklerdeki histopatolojik bulguları azalttığı histopatolojik yöntemlerle gösterilmiştir. Kronobiyoloji, Amfoterisin B, Fare, Candida, Nefrotoksisite INVESTIGATION OF THE INFLUENCE OF AMPHOTERICIN B IN MICE INFECTED WITH CANDIDA ALBICANS BY MEANS OF CHRONOTHERAPY Our research determined the effect of AmB treatment by means of chronobiology on mice kidneys whose infection and pathogenesis were infected by Candida. In our study, 32 experimental and 7 control mice were infected with clinical C. albicans strains (8 log CFU/ ml) and divided into 6 groups. 24 hours after infection, the 1st group control mice were treated with saline (0.2 ml/ day/ ip) at 0800, the 2nd group control mice were treated with saline (0.2 ml/ day/ ip) at 1800, the 3rd group mice were treated with AmB (1 mg/ kg/ day/ ip) at 0800, the 4th group mice were treated with AmB (1 mg/ kg/ day/ ip) at 1800, the 5th group mice were treated with AmB (0.5 mg/ kg/ day/ ip) at 0800, the 6th group mice were treated with AmB (0.5 mg/ kg/ day/ ip) at 1800 for 3 days. 10 healthy test and 4 healthy control mice were used on renal toxicity of AmB evaluation with chronotherapy. The 1st group control mice were administered with saline (0.2 ml/ day/ ip) at 0800, the 2nd group control mice were administered with saline (0.2 ml/ day/ ip) at 1800, the 3rd group mice were administered with AmB (5 mg/ kg/ day/ ip) at 0800, the 4th group mice were administered with AmB (5 mg/ kg/ day/ ip) at 1800 for 4 days. At 1800, mice which were treated with AmB (0.5 mg/ kg/ day/ ip) significantly decreased number of Candida on kidneys to compare to 0800 group(p<0.05). Mice which were treated with AmB (1 mg/ kg/ day/ ip) was no statistically significant difference between 0800 and 1800 groups (p>0.05). Mice which were treated with AmB (1 mg/ kg/ day/ ip) at 1800 on histopathological findings on kidneys significantly decreased to compared to 0800 group (p<0.05). At 1800, mice which were administered with high dose of AmB (5 mg/ kg/ day/ ip) significantly decreased level of serum BUN and creatinin to compared to 0800 group (p<0.05). At 1800, mice which were administered with high dose of AmB (5 mg/ kg/ day/ ip) significantly decreased on histopathological findings on kidneys to compared to 0800 group (p<0.05). Chronobiology, Amphotericin B, Mice, Candida, Nephrotoxicity