Browsing by Author "Kiliclioglu, Metin"
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Article Effect of Low- and High-Dose Methotrexate on Wound Healing in Rats(Acta Cirurgica Brasileira, 2025) Karasu, Abdullah; Kuscu, Yagmur; Kayikci, Caner; Yildirim, Serkan; Kuscu, Oguzhan; Kiliclioglu, MetinPurpose: To investigate the effect of intraperitoneal treatment with low- and high-dose methotrexate (MTX) on wound healing in rats. Methods: The study sample consisted of 54 healthy rats. Under aseptic conditions, skin wounds were created with two circular fullthickness punch tools, 10 mm in diameter, one on the right and the other one on the left of the dorsal vertebral line. The rats were randomly assigned to one of three main treatment groups. On the 0th day (2 hours before wound creation), 7th day, and 14th day, the control group received 0.3-mL saline, the low-MTX group received 3 mg/kg MTX, and the high-MTX group received 30 mg/kg MTX, all administered intraperitoneally. The wounds were evaluated seven, 14, and 21 days after injury through morphometrical, biochemical, histopathological, and immunohistochemical analyses. Results: MTX dose-dependently decreased the degree of inflammation and angiogenesis, tissue hydroxyproline level, and HSP70 and tumor necrosis factor-alpha expression in the early phase of wound healing. It also suppressed epithelialization and collagen 1 expression throughout the wound-healing process. Conclusion: The wounds treated with high-dose of MTX had statistically delayed wound closure on days 7, 14 and 21 compared to the saline group, while wounds treated with low-dose of MTX only had statistically delayed wound closure on day 14. In addition, weight loss was observed in rats treated with high-dose MTX, which was thought to reflect its toxicity. The dose-dependent adverse effect of MTX on wound healing may be due to its antiproliferative, antifibrotic, anti-inflammatory, and antiangiogenic effects.Article Self-Healing Demonstration in Imidacloprid Toxicity With Multibiomarkers and Biologic Pathways(Elsevier, 2023) Alak, Gonca; Yildirim, Serkan; Yeltekin, Asli Cilingir; Ucar, Arzu; Bolat, Ismail; Kiliclioglu, Metin; Atamanalp, MuhammedImidacloprid (IMI) pesticide has significant environmental and ecotoxicological pollution effects. Also, its high potential to enter the aquatic environment reveals the importance of early evaluation of the toxic effects of this compound. This study aimed to evaluate organ responses that can be associated with outcomes at higher levels of biological organization in fish. In this respect, the toxicity mechanism and recovery response process of IMI in rainbow trout (Oncorhyncus mykiss)' s different tissues (blood, brain, gill and liver) were analyzed with important biomarkers [(hematological indices (RBC, WBC, Hg, Hct, MCV, MCH, MCHC), antioxidant enzyme activities (SOD, CAT, GPx, GSH), MDA, DNA damage (8-OHdG), apoptosis (caspase 3), AChE, TNF alpha, interleukin 6, Nrf-2, NF-kB activities, histopathological and immunofluorescence analyses (NeuN, BDNF, JNK and Nop10]. Exposure to different concentrations of IMI caused a decrease in RBC, WBC, Hg and Hct levels in O. mykiss. The effect of the same application on brain, gill and liver tissues was determined as inhibitions in antioxidant enzyme activities (SOD, CAT and GPx) and GSH level, inductions on MDA level, DNA damage, caspase-3, TNF alpha, IL-6, Nrf-2 and NF-kB activities. As a result of three tissues' histopathological examination; the degeneration, necrosis and hyperemia in the brain and liver, adhesion, desquamation and inflammation in the lamellar epitheliums has been determined in company with stress-induced responses inducing DNA damage. In the reflection of this situation on histomap results, increases were recorded in BDNF and NeuN levels. In the recovery response, tissue damage profile and detoxification process were differentiated according to dose and marker, and it manifested itself with moderate and mild symptoms. These findings revealed that IMI-mediated oxidative stress was effective in the Nrf-2/GSH/NF-kB pathways, showing strong hemato/hepato, and neurotoxic effects. It has become clear that the severity of the effects caused by IMI exposure is felt more in the brain and liver tissues, and that such con-taminants should be taken into account in the risk assessment. During the post-exposure recovery period (after 15 days), AChE activity increased by 21% at high-dose administration. The recovery period was effective in regulating the oxidant/antioxidant balance of the organism by exhibiting serious induction/inhibition in each tissue and biomarker performance.