Browsing by Author "Kaynar, Ozgur"

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P2X7 receptor antagonist A-438079 alleviates oxidative stress of lung in LPS-induced septic rats.
(2023-03-24T00:00:00Z) Ozkanlar, Seckin; Ulas, Nergis; Kaynar, Ozgur; Satici, Emine
Sepsis is a deadly systemic inflammatory response of the body against infection resulting in immune response, cell differentiation and organ damage. Endotoxemia is one of the causes of sepsis-related acute respiratory distress and respiratory burst is an important generator of oxidants. Inflammation may be aggravated by overexpression of ATP-gated purinergic receptors (i.e., P2X7R) following cell damage. We aimed to evaluate the effects of P2X7R antagonist A-438079 on lung oxidative status and the receptor expression in endotoxemia of sepsis. Rats were subjected to sepsis by E. coli lipopolysaccharide (LPS) and treated with 15 mg/kg A-438079. The increase in circulatory IL-1β and IL-8 concentrations in LPS group confirmed the systemic inflammatory response to endotoxemia compared with Control groups (p < 0.001). Besides, there was an increase in P2X7R expression in lung tissue after LPS administration. Compared with Control groups, there were significant increases in the values of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) (p < 0.001), and myeloperoxidase (MPO) (p < 0.05) in lung tissue of LPS group. P2X7R expression in lung and IL-1β level in blood did not increase in LPS + A-438079 group. A-438079 decreased the lung levels of MDA, GSH, CAT and SOD (p < 0.001), and MPO (p < 0.01) in septic rats. As a result, administration of pathogen-associated LPS led to increased P2X7R expression into lung tissue and elevated lipid peroxidation product MDA with regard to oxidative damage. The P2X7R antagonist A-438079 alleviated the oxidative stress of lung with a balance of tissue oxidant/antioxidant factors in experimental sepsis in rats.
Protective effect of naringin against oxaliplatin-induced peripheral neuropathy in rats: A behavioral and molecular study.
(2022-09-01T00:00:00Z) Semis, Halil S; Kandemir, Fatih M; Caglayan, Cuneyt; Kaynar, Ozgur; Genc, Aydın; Arıkan, Sefik M
Oxaliplatin (OXL) is a chemotherapeutic drug used for metastatic and other types of cancer, but it causes peripheral neuropathy as a dose-limiting side effect. Herein, we used the rat model of OXL-induced peripheral neuropathy to demonstrate the protective effects of naringin (NRG) in this neuropathy. In this study, rats were injected with OXL (4 mg/kg, body weight, i.p.) in 5% glucose solution 30 min after oral administration of NRG (50 and 100 mg/kg, body weight) on the 1st, 2nd, 5th, and 6th days. OXL caused sensory and motor neuropathy (as revealed by the hot plate, tail flick, rota-rod, and cold hyperalgesia tests) in the sciatic nerve of rats. Coadministration of oral NRG alleviated OXL-induced sensory and motor neuropathy. Levels of superoxide dismutase, catalase, glutathione peroxidase, nuclear factor erythroid 2-related factor 2, Heme oxygenase-1, nuclear factor-κ B, tumor necrosis factor-α, interleukin-1β, Bax, Bcl-2, caspase-3, paraoxonase, mitogen-activated protein kinase 14, neuronal nitric oxide synthase (nNOS), acetylcholinesterase, and arginase 2 in the sciatic nerve tissues were assessed by real-time polymerase chain reaction. Moreover, the protein levels of caspase-3, Bax, Bcl-2, intercellular adhesion molecules-1, glial fibrillary acidic protein, and nNOS were examined by Western blot analysis. NRG treatment significantly improved all the above-mentioned parameters and reduced OXL-induced oxidative stress, inflammation, and apoptosis in the sciatic nerve tissue. In conclusion, this study demonstrated that NRG significantly attenuated OXL-induced peripheral neuropathy and might be considered as a new protective agent to prevent the OXL-induced peripheral neuropathy.
The protective effects of hesperidin against paclitaxel-induced peripheral neuropathy in rats.
(2021-12-15T00:00:00Z) Semis, Halil Sezgin; Kandemir, Fatih Mehmet; Kaynar, Ozgur; Dogan, Tuba; Arikan, Sefik Murat
Paclitaxel (PTX), which is widely used in the treatment of solid tumors, leads to dose limitation because it causes peripheral neuropathy. This study was conducted to evaluate the potential effects of hesperidin (HES), which has various biological and pharmacological properties, against PTX-induced sciatic nerve damage. For this purpose, Sprague Dawley rats were given PTX 2 mg/kg/b.w for 5 days, then 100 or 200 mg/kg/b.w HES for 10 days, and behavioral tests were conducted at the end of the experiment. The data obtained show that PTX-induced MDA, NF-κB, IL-1β, TNF-α, COX-2, nNOS, JAK2, STAT3, and GFAP levels decreased with HES administration. Moreover, it was observed that SOD, CAT, and GPx activities inhibited by PTX increased with HES administration. It was determined that PTX caused apoptosis in the sciatic nerve by increasing Caspase-3 and Bax levels and suppressing Bcl-2 levels. HES, on the other hand, showed an anti-apoptotic effect, increasing Bcl-2 levels and decreasing Caspase-3 and Bax levels. Also, it was observed that PTX could cause endoplasmic reticulum stress (ERS) by increasing PERK, IRE1, ATF-6, GRP78 and CHOP mRNA transcript levels, while HES could alleviate ERS by suppressing them. The results indicate that neuropathic pain associated with PTX-induced peripheral neuropathy can be alleviated by HES administration and that it is a promising compound for cancer patients. In addition, it is thought that the results of the present study contain information that will shed light for researchers regarding further studies to be conducted with HES.