Işik, Gözde; Çakir, Deniz Arca; Yirün, Anil; Erdemli-Köse, Selinay Başak; Özçelik, İbrahim; Erkekoǧlu, Pinar

Herpes simplex virus type 1 (HSV-1) infects an estimated 3.8 billion people under age 50 worldwide and establishes lifelong neuronal latency, leading to recurrent disease manifestations such as neonatal and genital herpes; yet no vaccine or curative therapy exists. This study evaluated the oxidative-stress-modulating effects of HSV-1 glycoprotein D (gD) alone or in combination with two antioxidant agents - ascorbic acid and sodium selenite - in a human neuroblastoma cell line. Key oxidative-stress markers - including total glutathione (GSH), malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), 8-isoprostane and protein carbonyl content - were quantified following exposure to "gD,""gD plus ascorbic acid", or "gD plus sodium selenite". Additionally, molecular docking analyses compared the binding affinities of ascorbic acid and sodium selenite for gD. Results showed that co-administration of ascorbic acid or sodium selenite with gD significantly elevated reactive oxygen species (ROS) levels compared to gD, while GSH and protein carbonyl concentrations remained unchanged. Intermediate lipid-peroxidation products did not differ significantly across treatment groups. Docking studies suggested that ascorbic acid exhibits a stronger potential for biologically relevant interaction with gD than sodium selenite, indicating a more pronounced antioxidant effect. These findings underscore the complexity of gD-induced oxidative pathways and highlight the need for further in vitro and in vivo investigations to delineate the toxicological impact of HSV-1 gD, as well as to extend analysis to other viral proteins involved in oxidative stress.

Yalçln, Hülya Tezel; Çaklr, Deniz Arca; Yirün, Anll; Sanajou, Sonia; Işlk, Gözde; Bozdemir, Özlem; Özçelik, Ibrahim; Güdül Bacanll, Merve; Zeybek, Naciye Dilara; Baydar, Terken

Melasma is a chronic condition that leads to the buildup of melanin pigment in the epidermis and dermis due to active melanocytes. Even though it is considered a non-life-threatening condition, pigment disorders have a negative impact on quality of life. Since melasma treatment is not sufficient and complicated, new treatment options are sought. Research on metformin and ascorbic acid suggested that they might be used against melasma in the scope of "drug repositioning."The MNT-1 human melanoma cell line was used to assess the effects of metformin, ascorbic acid, and metformin+ascorbic acid combination on cytotoxicity and oxidative stress. Melanin, cAMP, L-3,4-dihydroxyphenylalanine (L-DOPA) and tyrosinase levels were determined by commercial ELISA kits and tyrosinase gene expression was analyzed with RT-qPCR. Cytopathological evaluations were performed by phase contrast microscopy. Tyrosinase expression was determined by immunofluorescence (IF) staining of MNT-1 cells. The online service TargetNet was used for biological target screening. The parameters were not significantly altered by ascorbic acid applied at non-cytotoxic concentrations. On the contrary, metformin dramatically raised tyrosinase and intracellular ROS levels. Moreover, intracellular ROS levels and tyrosinase levels were found to be considerably elevated with the combined treatment. Also, potential metformin and ascorbic acid interactions were determined. According to the results, it can be said that these parameters were not significantly altered by ascorbic acid. On the contrary, metformin dramatically raised tyrosinase and intracellular oxidative stress levels. Moreover, intracellular oxidative stress and tyrosinase levels were elevated with the combined treatment. In conclusion, individual treatments of ascorbic acid or metformin may only provide a limited effect when treating melasma and extensive in vitro and in vivo research are required.

Yalçın, Hülya Tezel; Çakır, Deniz Arca; Yirün, Anıl; Sanajou, Sonia; Işık, Gözde; Bozdemir, Özlem; Özçelik, İbrahim; Bacanlı, Merve Güdül; Zeybek, Naciye Dilara; Baydar, Terken

Yeni, Yesim; Cicek, Betul; Hacimuftuoglu, Ahmet; Ozkaraca, Mustafa; Mokhtare, Behzad

Doxorubicin (DOX) is a commonly used medicine in cancer therapy. This drug accumulation in healthy tissues causes harmful clinical outcomes. Strategies that reduce oxidative damage, including alpha-lipoic acid (ALA) treatment, have been proposed to diminish toxic effects on healthy cells by raising the therapeutical effect of DOX on cancer cells. In this study, the preventive effects of ALA, against DOX-induced hepatorenal harm in rats were researched biochemically, molecularly, histopathological, and immunohistochemical. The experiment was designed for 10 days and 4 groups of 8 rats were created. ALA was administered orally to rats at a dosage of 200 mg/kg for 10 days and DOX was administered intraperitoneally at an only dosage of 30 mg/kg on day 8. To define oxidative stress, SOD, GSH, MPO, MDA, GPx, and CAT levels were evaluated. Hepatorenal harm was detected both histopathologically and by serum creatinine, ALT, ALP, AST, and urea analyses To detect the effect of inflammation, NF-κB, IL-1β, TNF-α levels, were defined in the liver, and AQP-2 and NPHS1 levels in the kidney. In addition, APG5L, Beclin 1, and LC3B expressions were determined immunohistochemically. It was determined that DOX-induced oxidative harm reduced and hepatorenal function markers improved in ALA-applied groups. It was also determined that ALA pretreatment had a regulative effect on NF-κB, AQP-2, TNF-α, NPHS1, and IL-1β levels and prevented the rise in DOX-induced LC3B, Beclin 1, and APG5L expression. Histopathological analysis showed that it prevented hepatorenal harm. As a result, ALA demonstrated its protective potential against DOX-induced hepatorenal toxicity.

Balci-Ozyur, Aylin; Yirun, Anil; Cakir, Deniz Arca; Ozcelik, Ibrahim; Bacanli, Merve; Ozkemahli, Gizem; Sabuncuoglu, Suna; Basaran, Nursen; Erkekoglu, Pinar

Introduction :Bisphenols are widely used in the production of polycarbonate plastics and resin coatings. Bisphenol A (BPA) is suggested to cause a wide range of unwanted effects and "low dose toxicity". With the search for alternative substances to BPA, the use of other bisphenol derivatives namely bisphenol F (BPF) and bisphenol S (BPS) has increased. Methods :In the current study, we aimed to evaluate the in silico predicted inhibitory concentration 50s (pIC50s) of bisphenol derivatives on immune and apoptotic markers and DNA damage on HepG2 cells. Moreover, apoptotic, genotoxic and immunotoxic effects of BPA, BPF and BPS were determined comparatively. Effects of bisphenols on apoptosis were evaluated by detecting different caspase activities. The genotoxic effects of bisphenols were evaluated by measuring the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-oxoguanine glycosylase (OGG1). To determine the immunotoxic effect of bisphenol derivatives, the levels of interleukin 4 (IL-4) and interleukin 10 (IL-10), transforming growth factor beta (TGF-β) and tumor necrosis factor-alpha (TNF-α), which are known to be expressed by HepG2 cells, were measured. Results: In silico data indicate that all of the bisphenols may cause alterations in immune and apoptotic markers as well as DNA damage at low doses. In vitro data revealed that all bisphenol derivatives could affect immune markers at inhibitory concentration 30s (IC30s). In addition, BPF and BPS may also have apoptotic immunotoxic effects. Conclusion :Both in silico and in vivo research are needed further to examine the toxic effects of alternative bisphenol derivatives.

Çolak, Deniz Altun; Uysal, Handan

Dioxin and dioxin-like compounds are known as a class of highly toxic and persistent environmental contaminants threatening human and animal health. In the present study, the protective effects of Coenzyme Q10 (CoQ10) and Resveratrol (RSV) against 2,3,7,8-TCDD, 1,2,3,7,8-PeCDD, 1,2,3,7,8,9-HxCDD, and 1,2,3,4,6,7,8,9-OCDD induced acute toxicity and measurement of oxidative stress were studied. Lethal doses of these chemicals were determined. Transheterozigot larvae of Drosophila melanogaster were treated using either dioxins (10 × 10-7 μg mL-1) or dioxins + CoQ10 (10 × 10-7 μg mL-1 + 150 μg mL-1) and dioxins + RSV (10 × 10-7 μg mL-1 + 100 μM). After dioxin treatment, antioxidant combination therapy with dioxins and CoQ10 or dioxins and RSV resulted in indicators of acute toxicity including a decrease in total oxidant status as compared to dioxins alone (p < 0.05). The combination treatment also produced a significant increase in total antioxidant status as compared to dioxins only (p < 0.05). Results indicate a potential role of dioxins for oxidative stress with acute toxicity and the protective performance of CoQ10 and RSV in the overall toxicity of dioxins including measuring oxidative stress.