Kürşad Yapar

Pyridine induction of cytochrome P450 1A1, iNOS and metallothionein in Syrian hamsters and protective effects of silymarin

An in vivo assessment for the protective effects of silymarin for pyridine toxicity was investigated through cytochrome P450 isoform CYP1A1 and inducible nitric oxide synthase (iNOS) activity prevention. Moreover, the effect of pyridine-induced oxidative stress on metallothionein I-II (MT), a scavenger of oxygen-derived free radicals, was investigated. Forty Syrian hamsters were allocated into 4 groups. Syrian hamsters were dosed with pyridine (400mg/kg) intraperitoneally with and without silymarin (200mg/kg daily by gavage) for 4 days. Pyridine induced diffuse degeneration and necrosis of the proximal and distal renal tubular cells; cloudy swelling, necrosis and hepatocellular atypia of the liver; and degenerative changes in the myocardium. The degree of pathological alterations was less severe with simultaneous silymarin application. CYP1A1, iNOS and MT expression levels were elevated in liver, kidney and heart in response to acute pyridine toxicity. Silymarin application abolished or significantly suppressed the induction of CYP1A1, iNOS and MT expressions in liver, kidney and heart of the pyridine-treated Syrian hamsters. Enhanced synthesis of MT by pyridine possibly implies a purposive cellular response to prevent damage caused by oxygen radicals. However, silymarin significantly reduced the oxidative-stress-inducing effect of pyridine as reflected by decreased synthesis of MT. These results suggest that through oxidant generation, pyridine may cause alteration of the metabolic ways, including nitric oxide-mediated CYP1A1 activity.

Dose-dependent effects of L-carnitine on blood sialic acid, mda and gsh concentrations in BALB/c mice

L-carnitine is an essential quarternary amine having an important role in the β-oxidation of fatty acids. Although L-carnitine was shown to be protective against toxic effects of some chemicals the dose-effect relationship with respect to its antioxidant action and protection from lipid peroxidation is unknown. To evaluate the dose-response profile of L-carnitine on blood sialic acid, glutathione and malondialdehyde concentrations, 40 mice were randomly allocated to 4 groups. Experimental mice were treated with intraperitoneal saline for 5 days (Group 1), L-carnitine at 100 mg/kg for 5 days (Group 2), L-carnitine at 250 mg/kg for 5 days (Group 3), L-carnitine at 500 mg/kg for 5 days (Group 4). Following the treatments, blood samples were collected, and blood glutathione, malondialdehyde and sialic acid concentrations were determined. L-carnitine provided an antioxidant action at doses of 100, 250 and 500 mg/kg with the strongest antioxidant action observed at 500 mg/kg dose. There was a significant increase in malondialdehyde and sialic acid concentrations at all doses of Lcarnitine with the highest effect seen at 500 mg/kg dose. In addition, Lcarnitine caused a dose-dependent elevation in glutathione level. These results suggest that L-carnitine applied at 500 mg/kg dose provides strong antioxidant action by increasing glutathione, malondialdehyde and sialic acid in BALB/c mice.

Effects of Different Nonsteroid Antiinflammatory Drugs on Free Triiodothyronin (fT3), Free Thyroxin (fT4) and Thyroid Stimulating Hormone Concentration in Rabbits

Bu çalışmada hekimliğimizde sıklıkla kullanım alanı bulan Flunixin meglimune, Carprofen ve Meloxicam gibi nonsteroidal antiinflamatorik ilaçların (NSAİD) beş günlük kullanım süresince serbest triiyodotronin (fT3), serbest troksin (fT4) ve troid stimulan hormon (TSH) konsantrasyonları üzerine olan etkilerinin belirlenmesi amaçlandı. Bu amaçla Yeni Zelanda ırkı, farklı cinsiyet ile benzer yaş ve ağırlıkta toplam 32 tavşan kullanıldı. Tavşanlar uygulama çeşitliğine göre 8’erli 4 gruba ayrıldı. Kontrol grubundaki tavşanlara serum fizyolojik, ikinci grup (FLU) tavşanlara 1.1 mg/kg dozda flunixin meglumine, üçüncü grup (CAR) tavşanlara 2.2 mg/kg dozda carprofen ve dördüncü grup (MEL) tavşanlara 0.2 mg/kg dozda meloxicam 5 gün süreyle günde bir kez İM uygulandı. Hormon konsantrasyonlarının tespiti amacı ile İlaç uygulamasından 4 saat sonra vena auricularis’ten usulüne uygun olarak antikoagulantsız ependorf tüplere alınan kan örnekleri 3000 rpm’de 10 dakika santrifüj edilerek serum elde edildi. Serbest T3, T4 ve TSH ölçümleri ticari ELISA kitler kullanılarak spektrofotometrik olarak yapıldı. Çalışma sonucunda NSAİD uygulanan her üç grupta ve beş günlük deneme süresince fT3 ve fT4 konsantrasyonlarının arttığı (p<0.001) ve bu artışların kontrol grubuna göre istatistiksel olarak değişik seviyelerde (p<0.05, p<0.01 ve p<0.001) önemli olduğu belirlendi. TSH konsantrasyonlarının her üç grupta benzer şekilde azaldığı (p<0.001) ve bu düşüşün de kontrol grubuna göre istatistiksel olarak önem arz ettiği (p<0.001) görüldü. Sonuç olarak, hayvanlarda NSAİD kullanımı esnasında troid hormon seviyelerinde farklı yönde değişimler meydana gelebileceği ve bu değişimlerin teşhis ve tedavilerde olası hatalara yol açmamak amacıyla mutlaka göz önünde bulundurulması gerektiği kanaatine varıldı.