Qinolone grubu antibiyotiklerin kıkırdak dokusu üzerine etkileri
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Date
1995
Authors
Çavuşoğlu, İlkin
Journal Title
Journal ISSN
Volume Title
Publisher
Uludağ Üniversitesi
Abstract
Fluorokmolonlar, oldukça yeni ve gelişmekte olan bir antibiyotik grubudur. Antîmikrobiyal aktivite spektrumlannın genişliği, biyoyararhlığı, dokulara iyi penetre olmaları, uzun serum yan-ömürleri ve genel güvenilirliği, bu bileşikleri tercih edilen ajanlar durumuna getirmiştir. Ancak bu ajanların juvenil deney hayvanlarında kondrotoksisite göstermeleri nedeniyle çocuklarda, adolesanlarda, gebelerde ve emzirme döneminde kullanılmaları kontrendikedir. Kinolonlarm sahip olduğu bu toksik potansiyel, insanlar için henüz kanıtlanmamıştır. Bu çalışma, bir fluorokinolon olan oftoksasinin juvenil sıçanların eklem kıkırdağında oluşturduğu lezyonun, tedavi kesildikten sonra zaman içinde progresyonunu ve reversibilitesini araştırmak amacıyla yapıldı. Bu amaçla, 4 haftalık sıçanlara 7 gün boyunca 900 mg/kg/gün ofloksasin oral olarak verildi Deney grubundaki sıçanlar, ilaç uygulaması bittikten 1 gün (l.grup), 1 hafta (2.grup), 2 hafta (3.grup), 4 hafta (4.grup), 8 hafta (S.grup), 12 hafta (6.grup) ve 16 hafta (7.grup) sonra öldürülerek diz eklemleri çıkarıldı ve ışık mikroskobik inceleme için hazırlandı. Tüm deneklerde eklem kıkırdağında lezyon görüldü. İlk gruplarda (l.ve 2.grup) eklem kıkırdağının radiyer zonunda, yerleşik olan lezyon; asellüler, Safranin-O ve Toluidin blue ile ileri derecede boyanma azlığı gösteren, ödematöz matriks alanları şeklindeydi Bu asellüler alanlar, daha sonraki gruplarda (3.,4.,5. grup) kavite ve son gruplarda (6.ve 7.grup) ise erode alanlar şeklim akü. Lezyon çevresinde nekrotik, piknotik nukleuslu, büzülmüş sitoplazmalı dejenere hücrelerin yanısıra, hasarıonarmaya çalışan kondrosit kümeleri görüldü. İlaç kesildikten 4 ay sonra lezyon, eklem kıkırdağında geniş erozyonlar şeklinde, varlığını sürdürüyordu. Çalışmada elde edilen bulguların sonucunda, kmolonlarm oluşturduğu yaşa bağımlı bu olağandışı toksik etkinin, zaman içinde ağuiaşarak devam ettiği ve reversibilite göstermediği kanısına varıldı. İhsanlar için toksisite riskinin deney hayvanlarından daha az olduğu düşünülmesine karşm, bu konuda geçerli kanıtlar ortaya konana kadar, bu ilaçların kontrendikasyon grubunda, kar/zarar hesabı yapılmadan kullanılmaması gerektiği düşüncesindeyiz.
The fluoroquinolones are relatively new and rapidly developing class of antibiotic agents. Their broad spectrum of antimicrobial activity, bioavailability, penetration into tissues, long serum half-fives and general safety have made them attractive agents against numerous infectious diseases. However, because of me development of cartilage toxicity in juvenile laboratory animals which have given qirinolone antibacterials, their use in children, adolescents, pregnant and lactating women are contraindicated. The risk of chondrotoxic potential of quinolones in humans has not yet been documented. The study was performed to examine the development, progression and reversibility of the cartilage lesions in juvenile rats mat were given ofloxacin, a fluoroquinolone. For mis purpose, 4 week old rats were given orally 900mg/kg/day of ofloxacin for 7 days. The rats were divided into 7 groups according to their sacrification days. They were killed 1 day (group IX 1 week (group 2% 2 weeks (group 3), 4 weeks (group 4), 8 weeks (group 5), 12 weeks (group 6) and 16 weeks (group 7) after the last administration of ofloxacin and the knee joints were prepared for light microscopic examination. The lesions were demonstrated in the articular cartilage of all the animals. The lesion which was located in the middle zone was characterised with aceHular, oedematous matrix areas, with markedry decreased stamabifity with Safranin-O and Tohndine blue in the groups 1 and 2. In the groups 3, 4, and 5 cavity formation was observed and in the groups 6 and 7 these lesions turned to extensive erosions. Chondrocytes around the lesions were necrotic, shrunken and had pyknotic nuclei The chondrocyte clusters, observed besides these degenerated cells, weredecided as a response of articular cartilage to repair the damage. But the lesions were still persisting as extensive erosions 4 months after stopping the medication. With the results obtained from this study, we concluded mat mis extraordinary form of age-related qumolone-induced cartilage toxicity is not reversible and the damage is persisting with increasing severity in time. Though the risk for humans seems to be lower men laboratory animals we advise to use these drugs with great care, after doing the risk/benefit analyse, especially in the contraindication group.until the concerns over arthropathy are justified.
The fluoroquinolones are relatively new and rapidly developing class of antibiotic agents. Their broad spectrum of antimicrobial activity, bioavailability, penetration into tissues, long serum half-fives and general safety have made them attractive agents against numerous infectious diseases. However, because of me development of cartilage toxicity in juvenile laboratory animals which have given qirinolone antibacterials, their use in children, adolescents, pregnant and lactating women are contraindicated. The risk of chondrotoxic potential of quinolones in humans has not yet been documented. The study was performed to examine the development, progression and reversibility of the cartilage lesions in juvenile rats mat were given ofloxacin, a fluoroquinolone. For mis purpose, 4 week old rats were given orally 900mg/kg/day of ofloxacin for 7 days. The rats were divided into 7 groups according to their sacrification days. They were killed 1 day (group IX 1 week (group 2% 2 weeks (group 3), 4 weeks (group 4), 8 weeks (group 5), 12 weeks (group 6) and 16 weeks (group 7) after the last administration of ofloxacin and the knee joints were prepared for light microscopic examination. The lesions were demonstrated in the articular cartilage of all the animals. The lesion which was located in the middle zone was characterised with aceHular, oedematous matrix areas, with markedry decreased stamabifity with Safranin-O and Tohndine blue in the groups 1 and 2. In the groups 3, 4, and 5 cavity formation was observed and in the groups 6 and 7 these lesions turned to extensive erosions. Chondrocytes around the lesions were necrotic, shrunken and had pyknotic nuclei The chondrocyte clusters, observed besides these degenerated cells, weredecided as a response of articular cartilage to repair the damage. But the lesions were still persisting as extensive erosions 4 months after stopping the medication. With the results obtained from this study, we concluded mat mis extraordinary form of age-related qumolone-induced cartilage toxicity is not reversible and the damage is persisting with increasing severity in time. Though the risk for humans seems to be lower men laboratory animals we advise to use these drugs with great care, after doing the risk/benefit analyse, especially in the contraindication group.until the concerns over arthropathy are justified.
Description
Keywords
Fhıorokinolonlar, Kondrotoksisite, Ofloksasin, Eklem kıkırdağı, Fluoroquinolone, Ofloxacin, Articular cartilage, Chondrotoxicity
Citation
Çavuşoğlu, İ. (1995). Qinolone grubu antibiyotiklerin kıkırdak dokusu üzerine etkileri. Yayınlanmamış doktora tezi. Uludağ Üniversitesi Sağlık Bilimleri Enstitüsü.