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Öğe Ameliorative effects of crocin on tartrazine dye-induced pancreatic adverse effects: a biochemical and histological study(Springer Heidelberg, 2021) Erdemli, Zeynep; Altinoz, Eyup; Erdemli, Mehmet Erman; Gul, Mehmet; Gozukara, Harika; Gul, SemirThe present study aimed to analyze the impact of tartrazine (T) and crocin (Cr) applications on the pancreas tissues of the Wistar rats. A total of 40 Wistar rats were randomly divided into 4 groups with 10 rats in each group, including the Control, T, Cr, and T + Cr groups. After 3 weeks of application, the pancreatic tissues of the rats were removed under anesthesia and rat blood samples were obtained. Tissues were analyzed with biochemical and histopathological methods. It was determined that T administration increased malondialdehyde (MDA), total oxidant status (TOS), oxidative stress index (OSI), glucose, triglyceride, LDL, VLDL, and total cholesterol levels. However, it decreased reduced glutathione (GSH), total antioxidant status (TAS), superoxide dismutase (SOD), catalase (CAT), and HDL levels when compared with the other groups. It was observed that Cr administration significantly increased GSH, SOD, CAT, TAS, and HDL levels when compared with the control group. In the T group, histopathological changes were observed in pancreatic tissue, leading to damages in exocrine pancreas and islets of Langerhans and increased caspase-3 immunoreactivity (p <= 0.001). Co-administration of Cr and T brought the biochemical and histopathological findings closer to the control group levels. The administration of T induced damage in the pancreas with the administered dose and frequency. Cr can increase the antioxidant capacity in pancreas tissue. Co-administration of T and Cr contributed to the reduction of the toxic effects induced by T. It could be suggested that Cr administration ameliorated T toxicity.Öğe Ameliorative effects of crocin on the inflammation and oxidative stress-induced kidney damages by experimental periodontitis in rat(Mashhad Univ Med Sciences, 2021) Erdemli, Zeynep; Erdemli, Mehmet Erman; Gul, Mehmet; Altinoz, Eyup; Gul, Semir; Kocaman, Gulhan; Kustepe, Elif KayhanObjective(s): The present study aimed to investigate the effects of periodontitis on kidneys and the protective role of crocin in periodontitis-induced kidney damage. Materials and Methods: Ethics committee approval was obtained and 30 Wistar rats were randomly divided into 3 groups of 10 rats: Control (C), Periodontitis (P), and Periodontitis + Crocin (P + Cr). After the treatments, rat kidney tissues were incised under anesthesia and blood samples were collected. Biochemical and histopathological analyses were conducted on the samples. Results: Malondialdehyde (MDA), total oxidant status (TOS), and oxidative stress index (OSI) increased in P group rat kidney tissues; urea, creatinine, Tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin 1 beta (IL-1 beta) levels increased in the serum; glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and total antioxidant status (TAS) levels were reduced in rat kidney tissues, and renal histopathology deteriorated. In the P + Cr group, we observed improvements in biochemical and histopathological parameters when compared with the P group. Conclusion: Periodontitis (P) led to deterioration in oxidative stress parameters and histopathology by increasing the oxidants in kidney tissue. P also led to inflammation in the blood of the rats. Periodontitis + Crocin (P + Cr) administration alleviated the effects of P due to powerful antioxidant anti-inflammatory properties. Cr could be employed as a protective agent in P-induced inflammation and oxidative damage.Öğe A bioactive product lipoxin A4 attenuates liver fibrosis in an experimental model by regulating immune response and modulating the expression of regeneration genes(Aves, 2019) Kurtoglu, Elcin Latife; Kayhan, Basak; Gul, Mehmet; Kayhan, Burcak; Kayhan, Meral Akdogan; Karaca, Zeynal Mete; Yesilada, ElifBackground/Aims: Lipoxin A4 (LXA4), an anti-inflammatory lipid mediator, regulates leukocyte cellular activity and activates gene transcription. The therapeutic effect of LXA4 on liver fibrosis and its mechanism on the immune system are largely unknown. Because the regenerative capacity of hepatocytes in acute and chronic liver failure models of mouse increases by silencing MKK4, we aimed to investigate the effect of parenteral administration of LXA4 on the genes responsible for regeneration of liver, namely MKK4, MKK7, and ATF2, and visualize the therapeutic effects in an experimental model. Materials and Methods: Fibrosis was induced in mice by administration of thioacetamide (TAA). LXA4 was administered during the last two weeks of fibrosis induction. The fibrosis level was measured by Knodell scoring. The liver function was measured by analyzing serum ALT, AST, and AP levels. Expression levels of genes responsible for liver fibrosis (TGF-alpha) and cell regeneration (MKK4, MKK7, and ATF2) have been measured by RT-PCR analysis. Inflammatory and anti-inflammatory cytokine levels were measured in serum samples and liver homogenates by Enzyme Linked Immunosorbent Assay (ELISA). Ultrathin sections were examined using a transmission electron microscope and analyzed. Results: We observed significant healing in liver of the LXA4-treated group, histologically. This finding was in parallel with reduction of serum ALT, AST, but not AP levels. TGF-alpha and MKK4 expressions were significantly reduced in the LXA4-treated group. Administration of LXA4 caused significant elevation of IL-10 in systemic circulation; however, that elevation was not detected in liver homogenates. Nevertheless, significant reductions in TNF-alpha and IL-17 have been observed. Conclusion: The anti-inflammatory effect of LXA4 maintains the regenerative capacity of liver during fibrosis in an experimental liver fibrosis model. LXA4 may be therapeutically beneficial in liver fibrosis.Öğe Can crocin play a preventive role in Wistar rats with carbon tetrachloride-induced nephrotoxicity?(Mashhad Univ Med Sciences, 2018) Erdemli, Mehmet Erman; Gul, Mehmet; Altinoz, Eyup; Aksungur, Zeynep; Gul, Semir; Bag, Harika GozukaraObjective(s): To investigate protective role of crocin by attempting to create nephrotoxicity with carbon tetrachloride. Materials and Methods: Ethics committee approval was obtained and 50 male Wistar rats were randomly divided into 5 groups that included 10 rats each: Control, Corn oil, Crocin, Carbon tetrachloride (CCl4), and Crocin + Carbon tetrachloride. Following the experiments, the rats were decapitated under anesthesia and incised kidney tissues were subjected to biochemical and histological examinations. Results: In the CCl4 administered group, MDA, TOS, Bun, and creatinine levels increased, GSH, SOD, CAT, and TAS levels decreased (P <= 0.05), glomerular collapse in kidney sections, narrowing and local occlusion in Bowman's space in certain glomeruli, inflammatory cell infiltration and congestion were observed when compared to all other groups. There was a significant decrease in increased MDA, TOS, Bun, and creatinine levels, and a significant increase in decreased GSH, SOD, CAT, and TAS levels in CCl4 + crocin administered group compared to the CCl4 group (P <= 0.05), local minimal glomerular damage, tubular damage, inflammatory infiltration, and vascular collagen symptoms were observed in kidney sections, however significant improvement was observed in damage findings when compared to the CCl4 group. Conclusion: At this dose and time interval, against a highly toxic chemical such as CCl4, crocin was able to suppress oxidative stress by playing a protective role in the kidney tissue.Öğe Crocin (active constituent of saffron) improves CCl4-induced liver damage by modulating oxidative stress in rats(Walter De Gruyter Gmbh, 2019) Cosgun, Binnaz Elif; Erdemli, Mehmet Erman; Gul, Mehmet; Gul, Semir; Bag, Harika Gozukara; Erdemli, Zeynep; Altinoz, EyupBackground: CCl4 is a widely used xenobiotic for the purpose of causing liver damage in experimental studies. In this study, we aimed to reveal the effects of crocin on liver injury caused by CCl4 via free radical scavenging properties. Materials and methods: Animals were divided into five groups of 10: control; corn oil; crocin; CCl4 ; CCl4 + crocin. Tissue samples were carefully removed and separated for biochemical and histological investigations. Results: CCl4 administration led to significant increases in MDA, SOD, CAT and TOS in liver tissue, and AST, ALT and ALP levels in plasma (p <0.05). In addition, CCl4 caused significant decreases in GSH and TAS (p < 0.05). When animals were treated with crocin, high MDA, SOD, CAT, TOS levels, and AST and ALP activities decreased and GSH and TAS levels increased. Control group exhibited normal histological appearance; however extensive necrosis areas were detected in the CCl4 group. In the CCl4 +crocin group, pathological changes were markedly decreased and the appearance of liver tissue was almost similar to the control groups. Conclusion: Our results showed that crocin suppresses oxidative stress with antioxidant properties and has a protective effect on tissue damage caused by CCl4.Öğe Crocin attenuates oxidative and inflammatory stress-related periodontitis in cardiac tissues in rats(Wroclaw Medical Univ, 2021) Kocaman, Gulhan; Altinoz, Eyup; Erdemli, Mehmet Erman; Gul, Mehmet; Erdemli, Zeynep; Zayman, Emrah; Bag, Harika Gozde GozukaraBackground. Periodontitis, a chronic inflammatory disease affecting the supporting tissues around the teeth, causes significant inflammatory and oxidative changes in cardiac tissue. Crocin is the active constituent of Crocus sativus (saffron) which has antioxidant properties and is protective against cardiovascular disturbances. Objectives. The present study aimed to investigate the protective effects of crocin on periodontitis-induced oxidative/inflammatory cardiac degeneration in rats in vivo. Materials and methods. Thirty female Sprague Dawley rats were randomly divided into 3 groups: control group, periodontitis group (PD) and periodonditis plus crocin group (PD+Cr). Experimental periodontitis was induced by placing silk ligatures on the maxillary second molar teeth for 30 days. Afterward, crocin (100 mg/kg body weight/day) was administered to the PD+Cr group and saline was administered to the PD group and the control group for 15 days. The subjects were sacrificed on the 45th day. Results. Histological and biochemical analyses demonstrated that inducing periodontitis caused obvious damage to cardiac tissues which was significantly ameliorated by crocin (p < 0.05). Significant improvements in bone resorption parameters (cross-linked C-telopeptide of type I collagen and bone alkaline phosphatase) were also observed in the PD+Cr group (p < 0.05). In addition, crocin caused significant reductions of malondialdehyde levels and total oxidant score while antioxidant levels (glutathione, superoxide dismutase, total antioxidant score, and catalase) were significantly higher in PD+Cr group (p < 0.05). Conclusions. This study reveals that periodontitis may cause oxidative damage in cardiac tissue and crocin improves periodontitis-induced degenerative changes in heart tissue, which is associated with its antioxidant properties.Öğe Crocin protects intestine tissue against carbon tetrachloride-mediated oxidative stress in rats(Aepress Sro, 2018) Cosgun, Binnaz E.; Erdemli, Mehmet E.; Gul, Mehmet; Gul, Semir; Bag, Harika G.; Aksungur, Zeynep; Altinoz, EyupSaffron is used in traditional medicine for its hypolipidemic, anti-inflammatory and anti carcinogenic properties as a natural remedy in treatment of diseases. The objective of the present study was to demonstrate the protective effect of crocin (one of the main ingredients of saffron) on carbon tetrachloride (CCl4) damage in intestinal mucosa. MDA, GSH, SOD, CAT, TAS and TOS levels were measured in experimental animal tissue samples and these were compared with histologic lesions induced by CCl4.CCl4 caused an increase in MDA, SOD, CAT and TOS levels and a significant decrease in GSH and TAS levels in rat intestinal tracts. After crocin treatment, serious improvements were observed in histological lesions and biochemical results in the intestinal tract. In conclusion, crocin inhibited the toxic effects induced by CCl4 in the intestine by its strong antioxidant properties.Öğe The effects of acrylamide and vitamin E on kidneys in pregnancy: an experimental study(Taylor & Francis Ltd, 2019) Erdemli, Mehmet Erman; Aksungur, Zeynep; Gul, Mehmet; Yigitcan, Birgul; Bag, Harika Gozukara; Altinoz, Eyup; Turkoz, YusufObjectives: The objective of this study is to investigate possible damages to kidney tissues of pregnant rats and their fetuses exposed to acrylamide during pregnancy and possible protective effects of vitamin E against these damages. Material and methods: Rats were randomly assigned to five groups of control, corn oil, vitamin E, acrylamide, vitamin E + acrylamide, six pregnant rats in each. Mother and fetal kidney tissues were examined for malondialdehyde (MDA), reductase glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), total antioxidant status (TAS), total oxidant status (TOS), urea, creatine, trace elements such as Zn and Cu in the serum and histopathological analyses were conducted. Results: It was determined that acrylamide, administered during pregnancy, statistically significantly increased MDA and TOS levels, maternal serum urea, creatinine, and Zn levels, while it decreased GSH, TAS, SOD, and CAT levels (p <= .05) when compared with all other groups in the kidney tissues of pregnant rats and their fetuses and caused tubular degeneration, hemorrhage, narrowing, and closure in Bowman's space, and, in the E vitamin group, it statistically significantly increased GSH, TAS, SOD, CAT, urea, creatinine, and Zn levels when compared with other groups and lowered TOS and MDA levels to those of the control group (p < .05) and there were no differences between the groups histologically. Conclusion: It was observed that acrylamide administered during pregnancy caused oxidative stress in kidney tissues of mother rats and their fetuses, resulting in tissue damage, and vitamin E application, which is considered to be a powerful antioxidant, inhibited oxidative stress.Öğe Effects of Cerebral Glucagon Administration on Blood Glucose Homeostasis in Rats(Wiley, 2023) Tanbek, Kevser; Yilmaz, Umit; Gul, Mehmet; Koc, Ahmet; Sandal, Suleyman[No abstract available]Öğe Hepatoprotective effects of crocin on biochemical and histopathological alterations following acrylamide-induced liver injury in Wistar rats(Elsevier France-Editions Scientifiques Medicales Elsevier, 2017) Gedik, Sema; Erdemli, Mehmet Erman; Gul, Mehmet; Yigitcan, Birgul; Bag, Harika Gozukara; Aksungur, Zeynep; Altinoz, EyupThe objective of the present study is the treatment of oxidative damage caused by acrylamide induced oxidative stress in rats with the administration of a strong antioxidant, namely crocin. High acrylamide (AA) levels have genotoxic, carcinogenic and neurotoxic effects on living organisms. In the present study, 40 Wistar rats were randomly divided into four equal groups. These groups were control, acrylamide (25 mg/kg), crocin (50 mg/kg), acrylamide + crocin (25 mg/kg acrylamide and 50 mg/kg crocin) groups. At the end of the application, biochemical and histological variations were examined in liver and blood samples. It was observed that acrylamide administration significantly decreased liver GSH and TAS levels when compared to the control group. On the contrary, it was also observed that AST, ALT, ALP, SOD and CAT activities and TOS and MDA levels increased as a result of acrylamide administration. Histopathological examinations demonstrated inflammatory cell infiltration, hepatocellular necrosis and hemorrhage areas in AA group liver sections. Furthermore, intracytoplasmic vacuolization was detected in hepatocytes. After crocin treatment, it was observed that GSH and TAS levels increased while AST, ALT, ALP, SOD and CAT activities and TOS and MDA levels decreased. Significant decreases were observed in inflammatory cell infiltration and vascular congestion in liver sections and intracytoplasmic vacuolization in hepatocytes after the crocin treatment, while no hepatocellular necrosis and hemorrhages were observed. In the present study, it was demonstrated that crocin treatment removed acrylamide induced liver damage due to the strong antioxidant properties of crocin.Öğe Intracerebroventricular BDNF infusion may reduce cerebral ischemia/reperfusion injury by promoting autophagy and suppressing apoptosis(Wiley, 2024) Yilmaz, Umit; Tanbek, Kevser; Gul, Semir; Koc, Ahmet; Gul, Mehmet; Sandal, SuleymanHere, it was aimed to investigate the effects of intracerebroventricular (ICV) Brain Derived Neurotrophic Factor (BDNF) infusion for 7 days following cerebral ischemia (CI) on autophagy in neurons in the penumbra. Focal CI was created by the occlusion of the right middle cerebral artery. A total of 60 rats were used and divided into 4 groups as Control, Sham CI, CI and CI + BDNF. During the 7-day reperfusion period, aCSF (vehicle) was infused to Sham CI and CI groups, and BDNF infusion was administered to the CI + BDNF group via an osmotic minipump. By the end of the 7th day of reperfusion, Beclin-1, LC3, p62 and cleaved caspase-3 protein levels in the penumbra area were evaluated using Western blot and immunofluorescence. BDNF treatment for 7 days reduced the infarct area after CI, induced the autophagic proteins Beclin-1, LC3 and p62 and suppressed the apoptotic protein cleaved caspase-3. Furthermore, rotarod and adhesive removal test times of BDNF treatment started to improve from the 4th day, and the neurological deficit score from the 5th day. ICV BDNF treatment following CI reduced the infarct area by inducing autophagic proteins Beclin-1, LC3 and p62 and inhibiting the apoptotic caspase-3 protein while its beneficial effects were apparent in neurological tests from the 4th day.Öğe Lipoxin A4 Improves Ultrastructural View of Liver and Reduces Expression Levels of MKK4 and TGF-? During Thioacetamide (TAA) Induced Fibrosis(Wiley, 2017) Kurtoglu, Elcin; Kayhan, Basak; Gul, Mehmet; Kayhan, Burcak; Akdogan, Meral; Yilmaz, Sezai[No abstract available]Öğe Prevention of toxic effects of orally administered tartrazine by crocin in Wistar rats(Taylor & Francis Ltd, 2021) Altinoz, Eyup; Erdemli, Mehmet Erman; Gul, Mehmet; Erdemli, Zeynep; Gul, Semir; Turkoz, YusufTartrazine is used in the pharmaceutical, cosmetic, and food industries worldwide, despite its many toxic effects. The therapeutic effects of crocin (50mg/kg/day) against tartrazine-induced (500mg/kg/day) oxidative damage in ileum and colon tissues in rats have been investigated. Malondialdehyde and total oxidant status levels elevated by tartrazine within the ileum and colon tissues were reduced with crocin treatment, while tartrazine decreased antioxidative parameters (glutathione, total antioxidant status, superoxide dismutase, and catalase) were reverted. Tartrazine-induced histopathological changes of ileum and colon tissues were ameliorated following crocin treatment. In conclusion, Tartrazine consumption elicited tissue injury via lipid peroxidation, and crocin ameliorated oxidative injury by its antioxidant and free radical scavenger properties.Öğe Protective effect of crocin on food azo dye tartrazine-induced hepatic damage by improving biochemical parameters and oxidative stress biomarkers in rats(Aepress Sro, 2019) Velioglu, Cigdem; Erdemli, Mehmet E.; Gul, Mehmet; Erdemli, Zeynep; Zayman, Emrah; Bag, Harika G.; Altinoz, EyupThe objective of the present study was to demonstrate the protective effect of crocin on the adverse effects of tartrazine on liver. Crocin is a carotenoid and a strong free radical scavenger. Forty rats were randomly divided into 4 groups (n = 10). The first group was the control group (C) and saline solution was administered to this group. The second group (Cr) was administered 50 mg/ kg crocin. The third group (T) was administered 500 mg/kg tartrazine. The fourth group (T+Cr) was administered the same doses of both crocin and tartrazine as the previous groups for 21 days. It was determined that tartrazine increased liver superoxide dismutase (SOD) activity, malondialdehyde (MDA) and total oxidant status (TOS) levels and catalase (CAT) activity, decreased glutathione (GSH), and total antioxidant status (TAS) levels. Furthermore, tartrazine administration resulted in significant increases in plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities and pathological changes in the liver. When tartrazine administered rats were treated with crocin for 21 days, the biochemical parameters improved, and liver tissues were restored. Thus, it was demonstrated that crocin had protective effects on the adverse effects caused by tartrazine administration.Öğe Protective effects of crocin on acrylamide-induced testis damage(Wiley, 2021) Gul, Mehmet; Kayhan Kustepe, Elif; Erdemli, Mehmet Erman; Altinoz, Eyup; Gozukara Bag, Harika Gozde; Gul, Semir; Gokturk, NurcanExposure to acrylamide (Ac) through food is almost inevitable and this kind of toxicity may cause lifelong harm. In present study, we researched effects of Crocin (Cr) on testis histopathology in Ac-induced testis of rats. Adult male rats were grouped as: group 1, 1 ml saline only; group 2, 50 mg/kg Cr only; group 3, 25 mg/kg Ac only and group 4, 25 mg/kg Ac + 50 mg/kg Cr. All administrations were given as 1 ml/day by gavage for 21 days. It was found that Ac adversely influenced the levels of FSH, testosterone and LH in the blood serum; malondialdehyde (MDA), total antioxidant status (TOS), oxidative stress index (OSI)/ glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), total antioxidant status (TAS) oxidant/antioxidant parameters in testis tissue (p < .01) and the histopathological parameters like Johnson's score, seminiferous tubule diameter, seminiferous epithelial height and H-score for caspase-3 immunoreactivity. In contrary, Cr treatment resulted in increase in testosterone, follicle stimulating hormone (FSH), luteinizan hormone (LH) levels and SOD, CAT, GSH, TAS levels (p < .01) and improved all the histopathological changes. In conclusion, Cr has a promising protective potential against Ac-caused toxic damages in testicular tissue.Öğe The protective role of crocin in tartrazine induced nephrotoxicity in Wistar rats(Elsevier France-Editions Scientifiques Medicales Elsevier, 2017) Erdemli, Mehmet Erman; Gul, Mehmet; Altinoz, Eyup; Zayman, Emrah; Aksungur, Zeynep; Bag, Harika GozukaraThe present study was conducted to investigate the changes in rat kidney tissues after administration of tartrazine (T) and crocine (Cr). The latter was applied for its protective properties. The present study was conducted with the approval of Inonu University, Faculty of Medicine, Experimental Animals Ethics Committee. Forty rats were randomly divided into 4 equal groups (Control, T, Cr, T + Cr). At the end of the experiment, the rats were decapitated. Biochemical and histopathological studies were conducted on excised rat kidney tissues. It was determined that there was a significant increase in MDA, TOS, SOD, CAT, Bun, Creatinine levels in tartrazine administered rat kidney tissues for 21 days, while GSH and TAS levels decreased (P <= 0.05) when compared to all other groups. On the other hand, it was identified that Cr administration statistically significantly increased GSH and TAS levels in rat kidney tissues when compared to all other groups and decreased MDA and TOS levels to control group levels (P < 0.05). T group kidney sections exhibited different degrees of collapse in the glomeruli. In most sections, different levels of inflammatory cell infiltration and vascular and capillary congestion were detected in peritubular interstitial tissue. It was determined that T leads to adverse effects on rat kidney tissues. Administration of Cr + T prevented T induced nephrotoxicity. Thus, it was concluded that Cr could be utilized as a new type of anti-tartrazine toxicity agent.
