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    Asprosin improved neuronal survival by suppressing apoptosis and enhancing the activity of the autophagy pathway in the MCAO model in rats
    (Verduci Editore s.r.l, 2024) Tanbek K.; Yuksel F.; Tekin S.; Tekin C.; Sandal S.
    OBJECTIVE: Cerebral ischemia (CI) is a condition in which metabolic stress increases when blood flow is interrupted in a part of the brain, resulting in oxygen and glucose deprivation. It is known that asprosin (Asp), secreted from adipose tissue during fasting, has an effect on some metabolic processes such as apoptosis, autophagy, and glucose metabolism. This study aimed to explain which of the cell death/survival Asp induces in the CI/reperfusion model. MATERIALS AND METHODS: In the study, 48 male Wistar Albino rats were divided into 6 groups: Sham, CI, Asp+CI, CI+Asp, CI+Asp+3-MA, and Asp+CI+3-MA (n=48). CI was created using the intraluminal filament technique for 60 minutes, autophagy inhibitor 3-MA (15 mg/kg/ day) and Asp (1 µg/kg/day) injections were administered 3 days before or 3 days during reperfusion. Beclin-1, ATG5, ATG7, p62, Bcl-2, Bax, active-caspase-3, and active-caspase-9 protein levels from brain tissues were determined by the Western-Blot method. The infarct area was determined by triphenyl tetrazolium chloride (TTC) staining. The Kruskal-Wallis’ test was used to compare differences between groups. p<0.05 was considered statistically significant. RESULTS: Compared to the Sham group, the increase in ischemic area and the decrease in Beclin-1, ATG-5, ATG-7, Bcl-2, Bax, active-caspase-3 and active-caspase-9 levels in the CI groups are statistically significant (p<0.05). The increase of Beclin-1, ATG-7, Bcl-2, and Bax levels in the Asp groups is statistically significant compared to the CI group (p<0.05). When Asp+CI groups and CI+Asp groups are compared, an increase in Beclin-1 levels in the Asp+CI group and the increase in Bcl-2, Bax, active-caspase-3/9 and ATG-5 levels in the CI+Asp groups are statistically significant (p<0.05). CONCLUSIONS: Asp has protective and therapeutic effects against CI/R damage. While applying Asp before ischemia activates the autophagy pathway more, applying it after ischemia protects the neuronal death/survival balance by activating the apoptosis pathway more. © 2024 Verduci Editore s.r.l. All rights reserved.
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    Effects of cholesterol and docosahexaenoic acid on cell viability and (Ca2+)i levels in acutely isolated mouse thymocytes
    (2009) Sandal S.; Tuneva J.; Yilmaz B.; Carpenter D.O.
    We investigated the effects of lipids on thymocyte function. The effects of application of cholesterol or docosahexaenoic acid (DHA), a C22, omega-3 (n-3) polyunsaturated fatty acid (PUFA), on viability and intracellular calcium concentrations of acutely isolated mouse thymocytes were investigated using flow cytometry. Cholesterol (100 ?M) caused significant cell death after 30-60 min whether or not calcium was present in the medium. Cell death was associated with an elevation of intracellular calcium whether or not calcium was present in the extracellular medium. However, the elevation of calcium concentration was not responsible for the cell death since calcium levels in the presence of ionomycin rose higher without significant cell death. DHA had similar actions but was more potent, causing significant cell death and elevation of calcium concentration within 5 min at 1 ?M. In the absence of extracellular calcium 1 ?M DHA caused 100% cell death within 15 min. Linolenic acid, a C18 omega-3 fatty acid also caused cytotoxicity at low concentrations whether or not albumin was present, but omega-6 or saturated C22 fatty acids were much less effective. These observations demonstrate that thymocyte viability is very sensitive to acute exposure to low concentrations of omega-3 fatty acids. Copyright © 2009 John Wiley & Sons, Ltd.
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    Effects of glucagon as a neurohormone on the central nervous system and glucose homeostasis
    (Verduci Editore s.r.l, 2024) Tanbek K.; Yilmaz U.; Gul S.; Koç A.; Gul M.; Sandal S.
    OBJECTIVE: This study aimed to elucidate the possible effects of the acute/ long-term infusion of glucagon in the brain as the regulatory role on the endocrine secretions of the pancreas. MATERIALS AND METHODS: Ninety male Wistar albino rats were divided as Control, artificial Cerebrospinal Fluid (aCSF) (120 min), Glucagon (120 min), pancreatic denervation (PD)+aCSF (120 min), PD+Glucagon (120 min), aCSF (7 days), Glucagon (7 days), PD+aCSF (7 days) and PD+Glucagon (7 days). Glucagon and solvent (aCSF) were administered after pancreatic denervation (PD) by Hamilton syringe and osmotic mini pump (1 µg/10 µl/min) in the third ventricle of the brain. RESULTS: Acute intracerebroventricular (icv) administration of glucagon resulted in an elevation of glucagon levels and a concurrent reduction in blood glucose levels. Furthermore, in both the PD+aCSF (7 days) and PD+Glucagon (7 days) groups, there was a notable decrease in propiomelanocortin (POMC) and agouti-related protein (AgRP). Significant changes were observed in feed consumption and body weight, as well as pancreatic glucagon levels, with a simultaneous decrease in insulin levels in the PD (7 days), Glucagon (7 days), and PD+Glucagon (7 days) groups. These alterations were statistically significant when compared to the control group (p<0.05). CONCLUSIONS: The research outcomes established that pancreas-secreted glucagon functions as a neurohormone within the brain, activating central pathways linked to blood glucose regulation. The presence of glucagon led to a decrease in POMC levels. Surprisingly, this reduction in POMC resulted in the suppression of AgRP. Contrary to expectations, the suppression of AgRP led to an increase in food intake rather than a decrease. As already highlighted in the results section, it was emphasized that POMC may play a more significant role than AgRP in influencing feeding behavior. © 2024 Verduci Editore s.r.l. All rights reserved.
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    Genotoxic effects of chlorpyrifos, cypermethrin, endosulfan and 2,4-D on human peripheral lymphocytes cultured from smokers and nonsmokers
    (2011) Sandal S.; Yilmaz B.
    Pesticides often cause environmental pollution and adverse effects on human health. We have chosen four structurally different pesticides (endosulfan, an organochlorine pesticide; chlorpyrifos, an organophosphate insecticide; cypermethrin, type II pyrethroid insecticide, and 2,4-dichlorophenoxyacetic acid, a chlorinated aromatic hydrocarbon acid pesticide) to examine and compare their effects on DNA damage in acutely cultured human lymphocytes by the comet assay. In addition, possible differences in response between smoking and nonsmoking subjects were also investigated. Venous blood samples were obtained from healthy male nonsmoker (n = 7) and smoker (n = 8) donors. Primary cultures of lymphocytes were prepared and test groups were treated with three different concentrations (1, 5, and 10 ?M) of endosulfan, chlorpyrifos, cypermehrin, and 2,4-D. DNA damage was assessed by alkaline comet assay. We determined an increase in the ratio of DNA migration in human lymphocyte cell cultures as a result of treatment with cypermethrin, 2,4-D and chlorpyrifos at high concentration. Endosulfan had no significant genotoxic effect even at 10 ?M concentration. We suggest that chlorpyrifos and cypermethrin are more potentially genotoxic than endosulfan and 2,4-D. Our findings also indicate that the only significant DNA damage between smokers and nonsmokers was observed in the 2,4-D-treated group. © 2010 Wiley Periodicals, Inc.