Browsing by Author "Kafa, Ilker Mustafa"

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    Anti-apoptotic and anti-oxidant effects of systemic uridine treatment in an experimental model of sciatic nerve injury
    (Türk Nöroloji Derneği, 2021-01-01) Khezri, Marzieh Karimi; Turkkan, Alper; Khezri, Marzieh Karimi; Koç, Cansu; KOÇ, CANSU; Salman, Berna; SALMAN, BERNA; Levent, Pinar; Cakir, Aysen; Kafa, Ilker Mustafa; Cansev, Mehmet; Bekar, Ahmet; ÇAKIR, AYŞEN; KAFA, İLKER MUSTAFA; CANSEV, MEHMET; BEKAR, AHMET; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Anatomi Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Fizyoloji Anabilim Dalı.; 0000-0002-6097-5585; 0000-0001-8309-0934; 0000-0003-2918-5064; AAA-4754-2022; ABX-9081-2022; A-6819-2018
    AIM: To investigate the anti-apoptotic and anti-oxidant effects of systemic uridine treatment in a rat model of sciatic nerve injury.MATERIAL and METHODS: Thirty-two adult male rats were equally randomized to Sham, Control, U100, and U500 groups. Sham rats received a sham operation by exposing the right sciatic nerve without transection, while those in the Control, U100, and U500 groups underwent right sciatic nerve transection followed by immediate primary anostomosis. Sham and Control groups received saline (0.9% NaCl) injections intraperitoneally (i.p.), while U100 and U500 groups received 100 mg/kg and 500 mg/kg uridine injections (i.p.), respectively, once a day for 7 days after the surgery. Rats in all the groups were sacrificed on the eighth day; sciatic nerve samples were analyzed for apoptosis by Western Blotting and for oxidation parameters including myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) by Enzyme-Linked Immunosorbent Assay (ELISA).RESULTS: Uridine treatment at the dose of 500 mg/kg significantly decreased as apoptosis determined by Caspase-3/Actin ratio and exhibited significant anti-oxidant effects as determined by decreased levels of MPO and MDA as well as increased levels of SOD, GPx, and CAT compared to controls. Uridine at 100 mg/kg was only found to decrease the Caspase-3/Actin ratio, although it significantly decreased MDA and increased CAT levels compared to controls.CONCLUSION: Treatment with uridine reduces apoptosis and oxidation in a rat model of sciatic nerve injury dose-dependently. Thus, uridine may be beneficial in peripheral nerve regeneration by exhibiting anti-apoptotic and anti-oxidant effects.
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    Protective effects of valproic acid, a histone deacetylase inhibitor, against hyperoxic lung injury in a neonatal rat model
    (Public Library Science, 2015-05-04) Cetinkaya, Merih; Cekmez, Ferhat; Tayman, Cuneyt; Canpolat, Fuat Emre; Kramer, Boris W.; Sarici, Serdar Umit; Cansev, Mehmet; Kafa, Ilker Mustafa; Yaylagul, Esra Orenlili; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Farmakoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Anatomi Anabilim Dalı.; Uludağ Üniversitesi/Fen Edebiyat Fakültesi/Biyoloji Bölümü.; 0000-0003-2918-5064; 0000-0001-8309-0934; 0000-0002-5206-1185; M-9071-2019; AAG-7125-2021; ABH-4915-2020; 8872816100; 8450193200; 55618956600
    Objective: Histone acetylation and deacetylation may play a role in the pathogenesis of inflammatory lung diseases. We evaluated the preventive effect of valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, on neonatal hyperoxic lung injury. Methods: Forty newborn rat pups were randomized in normoxia, normoxia+VPA, hyperoxia and hyperoxia+VPA groups. Pups in the normoxia and normoxia+VPA groups were kept in room air and received daily saline and VPA (30 mg/kg) injections, respectively, while those in hyperoxia and hyperoxia+VPA groups were exposed to 95% O2 and received daily saline and VPA (30 mg/kg) injections for 10 days, respectively. Growth, histopathological, biochemical and molecular biological indicators of lung injury, apoptosis, inflammation, fibrosis and histone acetylation were evaluated. Results: VPA treatment during hyperoxia significantly improved weight gain, histopathologic grade, radial alveolar count and lamellar body membrane protein expression, while it decreased number of TUNEL(+) cells and active Caspase-3 expression. Expressions of TGFβ3 and phospho-SMAD2 proteins and levels of tissue proinflammatory cytokines as well as lipid peroxidation biomarkers were reduced, while anti-oxidative enzyme activities were enhanced by VPA treatment. VPA administration also reduced HDAC activity while increasing acetylated H3 and H4 protein expressions. Conclusions: The present study shows for the first time that VPA treatment ameliorates lung damage in a neonatal rat model of hyperoxic lung injury. The preventive effect of VPA involves HDAC inhibition.