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Öğe Adipose-Derived Stem Cell Treatment Induces Early-Term Hes1 Upregulation in a Sox9- and Notch1-Independent Manner in a Rat Model of Bile Duct Ligation(Mdpi, 2026) Satilmis, Basri; Cicek, Egemen; Karakas, Serdar; Kutluturk, Koray; Kayhan, Elif; Gul, Mehmet; Yilmaz, SezaiBackground/Objectives: Bile duct ligation (BDL), characterized by marked inflammation and fibrosis, effectively mimics many clinical conditions and is a valuable tool for investigating biliary regeneration. Our objective was to clarify the therapeutic benefits of adipose-derived stem cell (ADSC) treatment and signaling pathways mediating regenerative processes in a rat model of BDL. Methods: The BDL model was performed on Sprague-Dawley rats, and ADSC was administered intrasplenically at a dose of 106 cells per animal. Liver function tests, gene and protein expression analyses, histological evaluation, and immunohistochemistry staining were performed to assess liver function, signaling pathways, inflammation, and fibrosis. Results: ADSC treatment returned liver function to sham levels. ADSC upregulated the Hes1 gene and protein expression in the early and late term. Inflammation, fibrosis, and total damage scores were decreased following ADSC treatment compared with the control. Immunohistochemistry staining revealed higher CD90, CD44, and CD29 stem cell marker expression in the ADSC treatment group. Conclusions: ADSC administration reduced fibrosis and biliary damage and restored liver function, potentially in a manner mediated by upregulated Hes1 expression, supporting its promise in biliary regeneration.Öğe Ameliorative Effects of Larazotide Acetate on Intestinal Permeability and Bacterial Translocation in Acute Pancreatitis Model in Rats(Springer, 2024) Karahan, Dogu; Harputluoglu, Muhsin Murat Muhip; Gul, Mehmet; Gunduz, Ayten; Ozyalin, Fatma; Inceoglu, Feyza; Satilmis, BasriBackground Intestinal barrier dysfunction in acute pancreatitis (AP) may progress to systemic inflammatory response syndrome (SIRS) and multi-organ failures by causing bacterial translocation. Larazotide acetate (LA) is a molecule that acts as a tight junction (TJ) regulator by blocking zonulin (Zo) receptors in the intestine. Aims In our study, we aimed to investigate the effects of LA on intestinal barrier dysfunction and bacterial translocation in the AP model in rats. Methods Thirty-two male Sprague-Dawley rats were divided into 4 groups; control, larazotide (LAR), AP, and AP + LAR. The AP model was created by administering 250 mg/100 g bm L-Arginine intraperitoneally 2 times with an hour interval. AP + LAR group received prophylactic 0.01 mg/mL LA orally for 7 days before the first dose of L-Arginine. For intestinal permeability analysis, fluorescein isothiocyanate-dextran (FITC-Dextran) was applied to rats by gavage. The positivity of any of the liver, small intestine mesentery, and spleen cultures were defined as bacterial translocation. Histopathologically damage and zonulin immunoreactivity in the intestine were investigated. Results Compared to the control group, the intestinal damage scores, anti-Zo-1 immunoreactivity H-Score, serum FITC-Dextran levels and bacterial translocation frequency (100% versus 0%) in the AP group were significantly higher (all p < 0.01). Intestinal damage scores, anti-Zo-1 immunoreactivity H-score, serum FITC-Dextran levels, and bacterial translocation frequency (50% versus 100%) were significantly lower in the AP + LAR group compared to the AP group (all p < 0.01). Conclusions Our findings show that LA reduces the increased intestinal permeability and intestinal damage by its effect on Zo in the AP model in rats, and decreases the frequency of bacterial translocation as a result of these positive effects.Öğe Ameliorative Effects of Quercetin on Tartrazine-Induced Hepatotoxicity in Rats: Insights Into Body Weight, Caspase Signaling, Cytokine Storm, Oxidative Stress, and Hepatocellular Proliferation(Wiley, 2026) Aylaz, Bulent; Erdemli, Zeynep; Gul, Mehmet; Bulut, Nilufer; Zayman, Emrah; Demirtas, Sezin; Erdemli, Mehmet ErmanProtective role of Quercetin against the possible harmful effects of Tartrazine, which is widely used. These doses have been studied for the first time in the literature. Rats were divided: Control, Tartrazine, Quercetin, and Tartrazine + Quercetin. The substances were administered for 30 days. Afterward, liver tissues and blood samples were collected and biochemically and histopathologically analyzed. An increase was noted in oxidant (MDA, SOD) and oxidative stress index parameters (TOS, OSI) while decreases were seen in antioxidant parameters (GSH, CAT, TAS), inflammation markers (TNF-alpha, IL-6), apoptosis (Caspase 3) and histopathological deterioration (heterochromatic with pyknotic nuclei, pericentral hepatocyte necrosis, and inflammatory cell infiltration) in liver tissue. There was also an increase in oxidative stress index, inflammation markers, and liver function tests (ALT, AST, ALP, Direct and Total Bilirubin) in serum samples of the tartrazine group. In the quercetin group, antioxidant parameters in liver tissue increased, whereas oxidant parameters, inflammation markers, and liver function tests in serum samples decreased. Improvements in both biochemical, blood, and histopathological parameters were observed with the concomitant administration of quercetin compared to the tartrazine group. Tartrazine caused hepatotoxicity by increasing oxidative stress, inflammation, and apoptosis in the liver tissues. Additionally, it led to widespread damage by elevating inflammation and worsening liver function test results in blood samples. Quercetin, however, showed strong antioxidant, anti-inflammatory, and apoptotic effects. We recommend daily use of quercetin to protect the liver from the harmful effects of tartrazine.Öğe Ameliorative effects of thymoquinone on the caspase 3, kidney function and oxidative stress tartrazine-induced nephrotoxicity(Pergamon-Elsevier Science Ltd, 2024) Erdemli, Zeynep; Gul, Mehmet; Gokturk, Nurcan; Kayhan, Elif; Demircigil, Nursena; Ozsoy, Eda Nur; Bag, Harika GozukaraFirst in the literature this study aimed to investigate the effects of Tartrazine, a common industrial food dye, on kidney and whether Thymoquinone has a protective effect in tartrazine-induced nephrotoxicity. The study conducted on the rats bred at I(center dot)non & uuml; University Experimental Animals Production and Research Center. Wistar albino rats were randomly divided into 4 groups, where each group included 8 rats: control, Tartrazine, Thymoquinone, and Tartrazine + Thymoquinone groups. The experiments continued for 3 weeks and then, kidney tissues and blood samples were collected from the rats under anesthesia. Malondialdehyde (MDA), super oxidized dismutase (SOD), total oxidant status (TOS), increase in Oxidative stress index (OSI), glutathione (GSH), Glutathione peroxidase (GSH-Px), catalase (CAT), Total antioxidant status (TAS) levels decreased in the kidney tissues collected from the tartrazine group. Serum Bun and Creatinine levels increased in the tartrazine group. Tartrazine administration damaged and degenerated the glomeruli and cortical distal tubes in the histopathology of kidney tissues, also different degrees of inflammatory cell infiltration were observed in the renal cortex and medulla. Thymoquinone and tartrazine administration improved both biochemical and histopathological parameters. Tartrazine administration induced nephrotoxicity. This could be observed with the increase in oxidant capacity and the deterioration of kidney functions. Thymoquinone was observed to demonstrate strong antioxidant properties. Thymoquinone could be used primarily as a protective agent against Tartrazine-induced toxicity.Öğe High-fat and carbohydrate diet caused chronic kidney damage by disrupting kidney function, caspase-3, oxidative stress and inflammation(Elsevier Science Inc, 2024) Erdemli, Zeynep; Gul, Mehmet; Kayhan, Elif; Gokturk, Nurcan; Bag, Harika Gozukara; Erdemli, Mehmet ErmanThe study aimed to compare the effects of a diet rich in fat, carbohydrates and protein on rat kidneys. The study was conducted on 40 Wistar albino rats bred at Ino center dot nu University Faculty of Medicine after the approval of the ethics committee. Rats were randomly divided into 4 groups: Control group, and the groups where the animals were fed with high carbohydrate, fat and protein rich feed. After the applications, the rat kidney tissues were removed by laparoscopy under anesthesia and blood samples were collected. 13 weeks long fat-rich and carbohydrate feed application had negative effects on oxidant-antioxidant balance, oxidative stress index, inflammation markers, kidney functions tests, histopathology and immunohistochemistry caspase-3 findings in rat kidney tissues, especially in the carbohydrate group when compared to the controls. Protein-rich feed, there were no significant difference in biochemical and histopathology compared to the control group. Fat and carbohydrate rich feed led to an increase in oxidative stress in rat kidney tissues. Oxidative stress led to nephrotoxicity, which in turn led to chronic kidney tissue damages. A more balanced and protein-rich diet instead of excessive sugar and fatty food intake could be suggested to prevent chronic kidney damage.Öğe Investigation of the effects of pinealectomy on acetylcholinesterase enzyme activity and oxidative stress in rat brain(Springer Japan Kk, 2025) Pekmez, Hidir; Ozkaya, Ahmet; Uckun, Mirac; Zayman, Emrah; Aydin, Merve; Canpolat, Sinan; Gul, MehmetThe pineal gland releases melatonin to regulate our body's circadian rhythm based on light and dark cycles. The pinealectomy (PINX) model is an experimental approach employed to investigate the potential impact of melatonin on various tissues and pathologies. In this study, acetylcholinesterase (AChE) enzyme activity levels, oxidative stress parameters, histopathological findings, and serum melatonin levels in rat brain tissue were evaluated following pinealectomy. 24 male Sprague Dawley rats were randomly divided into groups: control, Sham-Pinealectomy (SHAM), and PINX. Brain tissue samples were taken at the end of a 50-day experimental period to determine the parameters of AChE, glutathione s-transferase (GST), carboxylesterase (Ces) enzyme activities, and malondialdehyde (MDA), reduced glutathione (GSH) levels spectrophotometrically. Moreover, serum melatonin levels were measured, and tissues underwent standard histological analysis to determine the histopathological damage score. In this study, we found that the PINX group had decreased AChE and Ces enzyme activity, increased MDA, decreased GSH levels, and no change in GST enzyme activity. A relative decrease in serum melatonin levels was also observed in the PINX group. In the light microscopic examination of the brain tissue of pinealectomy rats, it was observed that the eosinophilic staining intensity increased, heterochromatic/pycnotic-looking neuron nuclei were prominent in the cortex layers and hippocampus, and perineural edematous areas were abundant. Excessive perineuronal edema, cytoplasmic eosinophilia, and heterochromatic/pycnotic nuclei were found based on the histopathological damage score. After pinealectomy, we observed an increase in oxidative stress and a decrease in AChE levels in the brain.Öğe Protective role of vitamin E against acrylamide-induced testicular toxicity from pregnancy to adulthood: insights into oxidative stress and aromatase regulation(Springer, 2024) Uremis, Muhammed Mehdi; Gultekin, Sevinc; Uremis, Nuray; Safak, Tarik; cigremis, Yilmaz; Gul, Mehmet; Turkoz, YusufAcrylamide (ACR) is a toxic chemical frequently encountered in daily life, posing health risks. This study aimed to elucidate the molecular-level mechanism of ACR's toxic effects on testicles and investigate whether Vitamin E can mitigate these effects. A total of 40 adult pregnant rats were utilized, divided into four groups: Control, ACR, Vitamin E, and ACR + Vitamin E. ACR and Vitamin E were administered to the mother rats during pregnancy and lactation, and to the male offspring until the 8th week post-birth. Serum hormone levels, oxidant-antioxidant parameters, histopathological examination of testicular tissue, and mRNA and protein levels of the testicular and liver aromatase gene were analyzed. Spermiogram analysis was conducted on the collected sperm samples from the male offspring. The results revealed that ACR exposure adversely affected hormone levels, oxidant-antioxidant parameters, histological findings, as well as aromatase gene and protein expressions. However, Vitamin E administration effectively prevented the toxic effects of ACR. These findings demonstrate that ACR application significantly impairs the reproductive performance of male offspring rats by increasing liver aromatase activity.Öğe Quercetin Exhibits Nephroprotective Properties Against Tartrazine-Induced Nephrotic Injury: Effects on Oxidative Stress, Kidney Function, Inflammation, Renal Tissue Morphology, and Apoptotic Pathway(Wiley, 2026) Erdemli, Zeynep; Gul, Mehmet; Bulut, Nilufer; Zayman, Emrah; Demirtas, Sezin; Karaaslan, Ezgi; Erdemli, Mehmet ErmanWe investigated first time in the literature the effects of tartrazine, a common industrial dye, and quercetin, a possible protective, on the kidneys. The rats were randomly assigned to the control, tartrazine, quercetin, and tartrazine + quercetin groups, with each group consisting of eight Wistar albino rats. The trials lasted for 1 month, after which kidney tissues and blood samples were collected. In the tartrazine group, increases were observed in malondialdehyde (MDA), superoxide dismutase (SOD), total oxidant status (TOS), oxidative stress index (OSI), tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), glomerular diameter and damage, histopathological damage score, glomerular and tubular caspase-3 immunoreactivity H-score, as well as serum urea, uric acid, and creatinine levels in the kidney tissue. Additionally, kidney tissue histopathology and apoptotic deteriorated in the same group. The deteriorated biochemical and histopathological parameters improved with quercetin administration. Tartrazine led to nephrotoxicity in rats, as indicated by kidney tissue oxidant capacity, inflammation, apoptosis, increased kidney function tests, and deterioration in histopathology. Quercetin exhibited strong antioxidant, antiapoptotic, and anti-inflammation activity and can be used as a protective agent against tartrazine-induced nephrotoxicity.Öğe The protective effects of thymoquinone against tartrazine-induced pancreatic injury and its impact on oxidative stress, caspase 3, blood glucose, insulin and cholesterol levels(Taylor & Francis Ltd, 2025) Erdemli, Zeynep; Zayman, Emrah; Gokturk, Nurcan; Gul, Mehmet; Demircigil, Nursena; Levent, Ayse Betul; Aylaz, BulentThe present study examined the effects of Tartrazine, a common industrial food colourant, on the pancreas and the protective role of Thymoquinone. Thirty-two Wistar albino male rats were randomly divided into four equal groups: Control, Tartrazine, Thymoquinone, and Tartrazine + Thymoquinone. The rats received Tartrazine and Thymoquinone treatments for 21 days. At the end of this period, pancreatic tissues and blood samples were collected for analysis. Tartrazine administration elevated malondialdehyde (MDA), total oxidant status (TOS), and oxidative stress index (OSI) levels, while decreasing glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), and total antioxidant status (TAS) in pancreatic tissue. It increased glucose, total cholesterol, triglycerides, and LDL levels, while decreasing insulin and HDL levels in blood samples. Tartrazine administration aggravated pancreatic histopathology and enhanced Caspase-3 positive immunoreactivity. Thymoquinone administration reduced the harmful effects of Tartrazine on biochemical and histopathological parameters. Tartrazine administration negatively impacted pancreatic tissue and blood samples. The increased oxidant capacity and oxidative stress led to these harmful effects. Conversely, Thymoquinone alleviated oxidative stress by increasing antioxidant capacity and could act as a protective agent.Öğe Thymoquinone played a protective role against tartrazine- induced(Mashhad Univ Med Sciences, 2023) Demircigil, Nursena; Gul, Mehmet; Gokturk, Nurcan; Kustepe, Elif Kayhan; Bag, Harika Gozukara; Erman, MehmetObjective(s): The current study, the first of its kind in the literature, aimed to observe the toxic effects of Tartrazine, a commonly used dyestuff in industries and foods, on the liver, and investigate whether this toxicity could be eliminated with thymoquinone coadministration. Materials and Methods: 32 male Wistar albino rats were procured from Inonu University Experimental Animals Breeding and Research Center. The rats were randomly assigned to 4 equal groups: Control group, Thymoquinone group, Tartrazine group, and Thymoquinone + Tartrazine group. Rat liver tissue and blood samples were obtained and biochemical and histopathological examinations were conducted on the samples. Results: Tartrazine administration increased the oxidant (malondialdehyde and superoxide dismutase) and oxidative stress index parameters (total oxidant status) in the liver tissue and decreased the antioxidant parameters (glutathione, glutathione peroxidase, catalase, and total antioxidant status) leading to histopathological problems (hematoxylin-eosin staining and Caspase-3 immunoreactivity) and inflammation (tumor necrosis factor-alpha and interleukin-6) in the serum samples. Thymoquinone, on the other hand, improved antioxidant and anti-inflammatory effects. Conclusion: At this time and dose, thymoquinone has a protective effect against tartrazine hepatotoxicity. Thymoquinone can be used as a protective agent against tartrazine toxicity.
