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Öğe Adverse effects of metamizole on heart, lung, liver, kidney, and stomach in rats(BioMed Central Ltd, 2024) Çiftel, Sedat; Süleyman, Bahadır; Mammadov, Renad; Coşkun, Reşit; Çoban, Taha Abdülkadir; Mokhtare, Behzad; Süleyman, Hali̇sBackground: Metamizole is banned in some countries because of its toxicity, although it is widely used in some European countries. In addition, there is limited information on its safety profile, and it is still debated whether it is toxic to the heart, lungs, liver, kidneys, and stomach. Aims: Our study investigated the effects of metamizole on the heart, lung, liver, kidney, and stomach tissues of rats. Methods: Eighteen rats were divided into three groups, wassix healthy (HG), 500 mg/kg metamizole (MT-500), and 1000 mg/kg metamizole (MT-1000). Metamizole was administered orally twice daily for 14 days. Meanwhile, the HG group received pure water orally. Biochemical, histopathologic, and macroscopic examinations were performed on blood samples and tissues. Results: Malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) in the lung and gastric tissues of MT-500 and MT-1000 groups were almost the same as those of the HG (p > 0.05). However, MDA levels in the heart and liver tissues of MT-500 and MT-1000 groups were higher (p < 0.05) compared to the HG, while tGSH levels and SOD, and CAT activities were lower (p < 0.05). MDA levels of MT-500 and MT-1000 groups in the kidney tissue increased the most (p < 0.001), and tGSH levels and SOD and CAT activities decreased the most (p < 0.001) compared to HG. Metamizole did not cause oxidative damage in the lung and gastric tissue. While metamizole did not change troponin levels, it significantly increased alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine levels compared to HG. Histopathologically, mild damage was detected in heart tissue, moderate damage in liver tissue, and severe damage in renal tissue. However, no histopathologic damage was found in any groups’ lung and gastric tissues. Conclusion: Metamizole should be used under strict control in patients with cardiac and liver diseases and it would be more appropriate not to use it in patients with renal disease.Öğe Effect of Rutin on Pulmonary Injury in Everolimus-Administered Rats Biochemical and Histopathological Evaluation(Asian Network Scientific Information-Ansinet, 2024) Demir, Omer Faruk; Suleyman, Zeynep; Suleyman, Halis; Coban, Taha Abdulkadir; Mokhtare, BehzadBackground and Objective: Everolimus is an anticancer agent that inhibits the Mammalian Target of Rapamycin (mTOR). It causes side effect such as pneumonia. This study aimed to evaluate rutin's effect on potential pulmonary injury in everolimus-administered rats biochemically and histopathologically. Materials and Methods: All rats were split into: Healthy (HG), everolimus-treated (EVR) (2 mg/kg) and rutin (50 mg/kg)+everolimus-treated (REV). Rutin was administered to the REV group and physiological saline was given orally tothe EVR and HG groups. As 1 hr later, everolimus 2 mg/kg was administered to REV and EVR groups. The process was repeated daily, 4 times weekly. Then, high dose anaesthesia was used to kill the rats and lung tissue samples were extracted. Oxidative stress and pro-inflammatory cytokine markers were examined and ANOVA test was applied. Results: Oxidative and inflammatory lung damage developed in the everolimus-treated rats. Rutin attenuated this oxidative and pro-inflammatory lung damage induced by everolimus. Rats administered with everolimus developed severe interstitial pneumonia, lymphoid hyperplasia and desquamation in lung tissues. This severe damage was reduced to mild level by administering rutin. Conclusion: The adding rutin to the treatment regimen for pulmonary damage associated with everolimus may have a preventive impact.Öğe Effect of vitamin D3 and a stinging nettle extract on the gastric tissue of rats administered with trinitrobenzene sulfonic acid(Czech Academy Agricultural Sciences, 2024) Gezer, Arzu; Aras, Sukran Yediel; Baygutalp, Nurcan Kilic; Sari, Ebru Karadag; Bedir, Gursel; Mokhtare, Behzad; Yilmaz, KadriyeIn this study, the effects of vitamin D-3 (Vit. D) and a stinging nettle [Urtica dioica L. (UD)] extract were examined using histopathological and immunohistochemical methods in the stomach tissues of an experimentally created rat model of Crohn's disease (CD). The CD model was created using trinitrobenzene sulfonic acid (TNBS). The animals in the study were divided into control, TNBS, TNBS+Vit. D, and TNBS+UD groups. At the end of the experiment, the animals were euthanised and their stomach tissues were evaluated for necrosis, degeneration, apoptosis, and inflammation. Additionally, an immunohistochemical method was applied to determine the somatostatin (SSTR), aquaporin-1 (AQP-1), caspase-3, and tumour necrosis factor-alpha (TNF-a) immunoreactivity in the gastric tissues. In the evaluations, degenerative and necrotic changes and mononuclear cell infiltration areas were observed in the TNBS group, but such changes could be improved with Vit. D and UD applications. The results suggest that the combination of the Vit. D and UD extract may have a protective and therapeutic role in mitigating TNBS-induced damage to the gastric tissues, potentially through the regulation of SSTR, AQP-1, caspase-3, and TNF-a expression. This indicates a promising avenue for further research and the exploration of these compounds in the context of gastrointestinal health.Öğe Formulation development of dual drug-loaded thermosensitive ocular in situ gel using factorial design(Springer, 2023) Polat, Heybet Kerem; Arslan, Aslıhan; Ünal, Sedat; Haydar, Muhammet Kerim; Aytekin, Eren; Gözcü, Sefa; Mokhtare, BehzadPurpose: To overcome the problems of low bioavailability of the drug associated with the short pre-corneal residence time, a thermoresponsive in situ gel system containing poloxamer P407, hydroxypropyl methylcellulose, and chitosan was developed to prolong the pre-corneal residence time of the drug. Methods: The central composite design was utilized to assess the effects of the concentration of poloxamer 407 hydroxypropyl methylcellulose and chitosan, the concentration of polymer, and the polymer type on the viscosity, pH, and gelation temperature, which were considered indicators of optimum formulations. Results: After model selection for response analysis, the quadratic model was found to be the best-fitting model for the relationship between independent factors and response variables. As a result of the central composite design, the optimized formulation contained 15.17% poloxamer 407 and 2.141% chitosan. Viscosity 25 °C = 2199.4 ± 26.2, viscosity 35 °C = 15,487.2 ± 117.4, pH = 6.5 ± 0.01, and gelation temperature °C = 33.3 ± 0.47 were obtained. The ex-vivo study revealed that the BRN formulation containing flurbiprofen-cyclodextrin inclusion complex has higher corneal penetration (P < 0.01). The cytotoxicity of ARPE-19 cells and irritation studies, as measured by in situ gel, was found to be acceptable. In lipoxygenase studies, the effectiveness of the BRN formulation was found to be significantly higher than other formulations (P < 0.01). Conclusions: It is thought that the BRN formulation may be an alternative to the treatment of ocular allergic disease.Öğe Formulation development of Lornoxicam loaded heat triggered ocular in-situ gel using factorial design(Taylor and Francis Ltd., 2023) Polat, Heybet Kerem; Ünal, Sedat; Aytekin, Eren; Karakuyu, Nasıf Fatih; Pezik, Esra; Haydar, Muhammet Kerim; Mokhtare, BehzadObjective: In the current research, lornoxicam-loaded in situ gels were developed, and their potential usage in ocular inflammation was evaluated. Significance: Lornoxicam cyclodextrin complex prepared with hydroxypropyl methylcellulose and poloxamer P407 because of the low viscosity of in situ gels to provide easy application. However, washing and removing it from the ocular surface becomes difficult due to the gelation formation with heat. Methods: A three-level factorial experimental design was used to evaluate the effects of poloxamer 407 concentration, polymer type, and polymer concentration on viscosity, pH, gelation capacity, gelation time, and gelation temperature, which were considered the optimal indicators of lornoxicam-containing formulations. Results: As a result of the three-level factorial experimental design, the optimized formulation contained 15 (%w/v) poloxamer 407 and 1 (%w/v) hydroxypropyl methylcellulose. The optimize formulation viscosity 25 °C = 504 ± 49cP, viscosity 35 °C = 11247 ± 214cP, pH = 6.80 ± 0.01, gelation temprature = 35 ± 0.2 °C, and gelation time= 34 ± 0.2 s was obtained. In the in vitro release studies, 68% of lornoxicam was released with a burst effect in the first three hours; then, the release continued for eight hours with controlled release. Release kinetics of the formulations were modeled mathematically, and it was found to be compatible with the Korsemeyer-Peppas and Weibull models. In cell culture studies, cell viability at 100 µg/mL was 83% and 96% for NL6 and NL6-CD, respectively. In Draize’s in vivo test, no negative conditions occurred in rats. Conclusions: Therefore, the NL6-CD formulation has the potential to be a favorable option for treating ocular inflammation.Öğe Harnessing silk fibroin microparticles for metformin delivery: A novel approach to treating corneal neovascularization(Editions de Sante, 2024) Polat, Heybet Kerem; Aytekin, Eren; Karakuyu, Nasıf Fatih; Çaylı, Yağmur Akdağ; Çalamak, Semih; Demirci, Nazire; Mokhtare, BehzadCorneal neovascularization (CV) poses significant challenges in ophthalmology, often leading to impaired vision and discomfort. Silk fibroin microparticles have emerged as promising candidates for drug delivery applications, owing to their biocompatibility, biodegradability, and controlled release characteristics. In the current research, metformin-loaded silk microparticles were developed, and their potential for treating corneal neovascularization was evaluated. Silk microparticles were prepared using silk fibroin and polyvinyl alcohol (PVA) at various weight ratios, facilitating phase separation to create a porous structure conducive to drug loading. Metformin (MT), a widely used antidiabetic agent with potential anti-angiogenic properties, was incorporated into the silk microparticles at different concentrations. The formulation termed TB (0.3 % MT loaded Microparticles) emerged as the most promising candidate was identified through comprehensive in vitro evaluations. In in vitro cytotoxicity studies, it was determined that all formulations provided cell viability above 80%, however, in permeability studies and encapsulation efficiency studies, TB was determined to be more effective than other formulations. TB demonstrated a particle size of approximately 8.9 ± 3.6 ?m and an encapsulation efficiency of 96.3 ± 2.1%. In vitro release studies revealed that TB exhibited a burst release of 62% within the initial two days, followed by sustained release over a period of 14 days, consistent with Peppas-Sahlin kinetics. Mathematical modeling further corroborated the diffusion mechanism underlying drug release from TB microparticles. In vivo studies on rats and histochemical analyzes on corneas showed that TB exhibited efficacy comparable to dexamethasone, a standard treatment for CV, despite being administered once daily. Histological analyses of corneal tissues revealed reduced neovascularization and inflammation in the TB-treated group, underscoring its therapeutic potential. Overall, our findings highlight the promise of metformin-loaded silk fibroin microparticles as a novel therapeutic approach for managing CV, offering sustained drug release and enhanced efficacy in treating this challenging ocular condition. © 2024Öğe Helichrysum Plicatum DC Subsp Plicatum Etanol Ekstraktının sıçanlarda Talyum Sülfatın neden olduğu testis toksisitesi üzerine etkilerinin belirlenmesi(Van Yuzuncu Yıl University, 2024) Ömür, Ali Doğan; Yıldırım, Betül Apaydın; Küçükler, Sefa; Mokhtare, Behzad; Karataş, Özhan; Özkaraca, Mustafa; Akarsu, Serkan AliIn this study, we aimed to determine the effects of the ethanol extract of Helichrysum plicatum DC plant on Thallium Sulfate (TS)-induced testicular toxicity in rats. For this purpose, a total of 24 Sprague Dawley rats, 6 each in four groups, were used in the study. Rats were administered a single dose of TS via IP and HPE via oral gavage for 8 days. After the administrations, the rats were sacrificed and blood and testicular tissues were collected. Testicular tissues were preserved for use in biochemical, histopathological, immunohistochemistry and in situ hybridization analyzes. The cauda epididymis was trimmed by separating from the testis and the resulting liquid was used for semen analysis. The sperm motility decreased and the rate of dead and abnormal spermatozoa increased in parallel to the increase (PÖğe Therapeutic Potential of Bacopa monnieri L. in Sciatic Nerve Ligation: Modulation of Regeneration and Oxidative Stress(2023) Al-Yaqoobı, Ziadoon; Altunlu, Öznur; Burul, Feyza; Topatan, Esma; Mokhtare, Behzad; Budak Savaş, Ayşenur; Yörük, Mehmet AliBacopa monnieri L. is a plant known for its neuroprotective properties with positive effects on neuronal regeneration and synaptic activity. In this study, the effects of Bacopa monnieri L. extract on the regeneration process in sciatic nerve injury, which is a peripheral nerve injury model, were investigated. Within the scope of this study, 18 Sprague–Dawley rats, each group containing six animals, were divided into three groups. Surgical ligation of the sciatic nerve was performed at the beginning of the experiment to induce sciatic nerve injury in the positive control and treatment groups. Following surgical intervention, the treatment group received a daily dose of 400 mg/kg extract for 15 days starting from the 14th day post surgery. The oxidative stress status in serum samples obtained from rats was investigated biochemically. Immunohistochemical measurements of tumor necrosis factor alpha and inducible nitric oxide synthase were also performed in the muscles surrounding the sciatic nerve. Upon examination of the results, it was observed that the treatment group exhibited a significant increase in antioxidant capacity compared to the control groups. Furthermore, the oxidant status in the treatment group was lower than that in the positive control group. Immunohistochemical examinations revealed an increase in tumor necrosis factor alpha- and inducible nitric oxide synthase immunoreactivity in the positive control group, while a decrease in the immunoreactivity of these inflammation markers was observed in the treatment group. In conclusion, Bacopa monnieri L. extract may contribute to recovery in peripheral nerve injury by regulating antioxidant and anti-inflammatory processes.Öğe Therapeutic Potential of Bacopa monnieri L. in Sciatic Nerve Ligation: Modulation of Regeneration and Oxidative Stress(Atatürk Üniversitesi, 2023) Al-yaqoobi, Ziadoon; Altunlu, Öznur; Burul, Feyza; Topatan, Esma; Mokhtare, Behzad; Savaş, Ayşenur Budak; Yörük, Mehmet AliBacopa monnieri L. is a plant known for its neuroprotective properties with positive effects on neuronal regeneration and synaptic activity. In this study, the effects of Bacopa monnieri L. extract on the regeneration process in sciatic nerve injury, which is a peripheral nerve injury model, were investigated. Within the scope of this study, 18 Sprague–Dawley rats, each group containing six animals, were divided into three groups. Surgical ligation of the sciatic nerve was performed at the beginning of the experiment to induce sciatic nerve injury in the positive control and treatment groups. Following surgical intervention, the treatment group received a daily dose of 400 mg/kg extract for 15 days starting from the 14th day post surgery. The oxidative stress status in serum samples obtained from rats was investigated biochemically. Immunohistochemical measurements of tumor necrosis factor alpha and inducible nitric oxide synthase were also performed in the muscles surrounding the sciatic nerve. Upon examination of the results, it was observed that the treatment group exhibited a significant increase in antioxidant capacity compared to the control groups. Furthermore, the oxidant status in the treatment group was lower than that in the positive control group. Immunohistochemical examinations revealed an increase in tumor necrosis factor alpha- and inducible nitric oxide synthase immunoreactivity in the positive control group, while a decrease in the immunoreactivity of these inflammation markers was observed in the treatment group. In conclusion, Bacopa monnieri L. extract may contribute to recovery in peripheral nerve injury by regulating antioxidant and anti-inflammatory processes.
