Osman GÖKALP, Ekrem ÇİÇEK, Aparslan GÖKÇİMEN, Nermin KARAHAN, Meral ÖNCÜ, Gülsen AYDIN

Histopatological changes in liver and renal tissues induced by different doses of diclofenac sodium in rats

: Non-steroidal anti-inflamatuar ilaçlar (NSAIDs) dünyada yaygın olarak kullanılırlar. Bu ilaçlar bazen yalnışlıkla yüksek ya da toksik dozda kullanılabilirler. Bu çalışmada, farklı dozlarda diclofenac sodium'un karaciğer ve böbrek dokuları üzerine etkilerini araştırmayı amaçladık. Wistar Strain cinsi ağırlıkları 200-220 gram olan 40 adet olgun Albino ratlar, her biri l O rattan oluşan 4 gruba ayrıldı. Kontrol grubu olan ratlara (n = 10) intramüsküler olarak l cc serum fizyolojik enjekte edildi. Diğer üç gruba diclofenac sodium'un farklı dozları'uygulandı. Birinci (n = 10), ikinci (n = 10) ve üçüncü (n = 10) grup ratlara 5 gün süre ile hergün 50, 100, 150 mg/kg, düşük, orta ve yüksek dozlarda diclofenac sodium intramüsküler olarak enjekte edildi. Beş günlük deney süresi sonunda hayvanlar ötenazi edildikten sonra nekropsileri yapılarak, karaciğer ve böbrek doku örnekleri histopatolojik inceleme için hazırlandı. Kontrol grubu ratların karaciğer ve böbrek dokularının histopatolojik incelenmesinde önemli değişiklikler gözlenmedi (P > 0,05). Diclofenac sodium tedavisi, karaciğer ve böbrek dokularını önemli derecede etkiledi (P < 0,001). Diclofenac tedavili bütün grupların, hematoksilen-eosin ile boyalı karaciğer kesitlerindeki histopatolojik değişiklikler: Karaciğer hücrelerinde bulanık şişkinlik ve hidropik dejenerasyon, fokal sinusoidal ve santral ven genişlemesi, portal alanlarda safra kanal proliferasyonu, mononükleer hücreînfiltrasyonu ile birlikte periportal mesafe genişlemesi, hiperemi, fokal nekrozlar ve doza bağlı fıbröz doku artışıydı. Diclofenac sodium tedavili bütün grupların böbrek dokularının tübüler epitel hücrelerinde bulanık şişkinlik ve hidropik dejenerasyon görüldü. Fakat, nekroz, peritübüler lenfosit infıltrasyonu, interstisiyumda fibröz doku artışı, hiperemi ikinci ve üçüncü gruplarda gözlendi. Yüksek doz diclofenac sodium verilen üçüncü grubun karaciğer ve böbrek dokularında görülen nekroz, hidropik dejenerasyon ve inflamasyon, düşük dozla karşılaştırıldığında, daha yaygın ve yoğun idi. Böbrek dokusunda ve karaciğerin periportal alanlarında düzensizliğe neden olan bağ dokusu artışı sadece yüksek doz alan grupta görüldü. Bu bulgular, yüksek doz diclofenac sodium'un karaciğer ve böbrek dokularında anlamlı değişikliklere neden olduğunu göstermektedir.

Farklı dozlarda diclofenac sodium'un ratların karaciğer ve böbrek dokusunda oluşturduğu histopatolojik değişiklikler

: Non-steroidal anti-inflammatory drugs (NSAIDs) are in common use worldwide. These drugs may sometimes be used in high or toxic doses by mistake. In this study we investigated the effects of different doses of diclofenac sodium on liver and renal tissues. Forty albino adult male Wistar rats weighing 200 to 220 g were divided equally into four groups. The rats in the control group (n = 10) were each intramuscularly injected with 1 cc of physiologic saline. The other three groups were given diclofenac sodium doses. The rats in the first (n = 10), second (n = 10) and third (n = 10) groups were intramuscularly injected with diclofenac sodium at a low, medium and high dose of 50, 100 and 150 mg/kg live weight/day, respectively, every day for 5 days. At the end of the experimental period (5 days), after the animals were sacrificed, they were autopsied and liver and kidney tissue samples were prepared for histopathologic assessment. No significant (P > 0.05) changes were observed in the histopathology of the liver or kidney tissues of the control rats. The diclofenac sodium treatment significantly (P < 0.001) affected the histopathology of both the liver and kidney. Histopathologic changes in the liver sections stained with hematoxylin and eosin in all diclofenac groups included claudy swelling and hydropic degeneration of the liver cells, focal sinusoidal and vena centralis dilatation, proliferation of the bile duct in portal areas, enlargement of the periportal area with mononuclear cell infiltration, hyperemia and dose-dependent fibrous tissues proliferation and focal necrosis. Cloudy swelling and hydropic degeneration were seen in the tubular epithelial cells of the kidney tissue of all diclofenac sodium treated groups. Necrosis, peritubular lymphocyte infiltration, stromal fibrous tissue proliferation and hyperemia were observed in the second and third groups. In the liver and kidney tissue of the third group, which was given a high dose of diclofenac sodium, necrosis, cloudy swelling and hydropic degeneration and inflammation were rather widespread and intensive, as compared to the group given a low dose. The increase in fibrous tissue in the kidney and liver that caused irregularities in the periportal areas was only seen in the group given a high dose. These results suggest that a high dose of diclofenac sodium causes meaningful changes in liver and kidney tissue.

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