Asprosin improved neuronal survival by suppressing apoptosis and enhancing the activity of the autophagy pathway in the MCAO model in rats.

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.

Effects of glucagon as a neurohormone on the central nervous system and glucose homeostasis.

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.

The role of miRNAs targeting K-ras and APC genes in colorectal cancer.

OBJECTIVES: The occurrence of abnormal expression patterns in different types of cancer suggests that micro RNAs (miRNAs) may play an important role in tumorigenesis. The aim of this study was to examine the expression levels of miRNAs known to be associated with the regulation of the expression levels of the APC and K-ras, which are important in the development of colorectal cancer (CRC). METHODS: The expression levels of miR-27, miR-663, miR-217, miR-181d, APC and K-ras in the serum, tumor and adjacent tumor-free (healthy) tissues of the patients and serum of the healthy controls were investigated with qRT-PCR. RESULTS: Expression levels of miR-217, mR-181d, miR-663, miR-27 and K-ras were found to be higher in CRC tissues than in adjacent tumor-free tissues of the patients. In patient serum samples, miR-663 levels were statistically more elevated than in controls. In patient tumor tissues, miR-217, miR-181d and miR-27 expressions were found to be higher. CONCLUSIONS: Increased miR-181d and miR-217 expression levels are associated with increased K-ras expression in the tumor tissues, and the expression of K-ras, which takes part as an oncogene in the CRC development, might be regulated by these miRNAs (Tab. 4, Ref. 33).

The effect of varicocoelectomy on the relationship of oxidative stress in peripheral and internal spermatic vein with semen parameters.

The aim of this prospective controlled study was to investigate the levels of reactive oxygen species (ROS), including asymmetric dimethylarginine (ADMA), oxidative stress index (OSI) and total oxidant capacity (TOC), and antioxidants with total antioxidant capacity (TAC) in peripheral and internal spermatic veins blood, the relationship of these factors with sperm parameters in the infertile varicocoele patients, and the amelioration effect of varicocoelectomy on these outcomes. Thirty-one primary infertile varicocoele patients and 31 fertile control patients evaluated for determining the levels of ADMA, TOC, OSI, superoxide dismutase (SOD), glutathione (GSH), TAC, and semen analysis. The patients' preoperative SOD, GSH and TAC levels, which were significantly lower than the controls, significantly increased postoperatively. Although SOD and GSH were significantly higher in spermatic vein compared to median cubital vein, TAC was significantly higher in median cubital vein. ADMA, TOC and OSI were significantly higher in the patient group. TOC and OSI were significantly higher in spermatic vein compared to median cubital vein. Postoperative TOC, OSI and ADMA reduced to the control levels. Total antioxidant capacity in the peripheral circulation and oxidative stress index in the internal spermatic vein could give an idea about the possible improvement in sperm count acquired by varicocoelectomy.

Beneficial effects of aminoguanidine on radiotherapy-induced kidney and testis injury.

This experimental study was designed to investigate both protective and therapeutic effects of aminoguanidine (AG), on radiotherapy (RT)-induced oxidative stress in kidney and testis. Forty rats were divided into five groups equally as follows: (i) control, (ii) RT, (iii) AG, (iv) AG+RT and (v) RT+AG group. Histopathological findings and biochemical evaluations, including tissue malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione (GSH), total oxidant status (TOS), total antioxidant capacity, oxidative stress index (OSI), blood urea nitrogen (BUN), serum creatinine (Cr) and testosterone levels, were determined. MDA, TOS and OSI were significantly higher in RT-treated groups, whereas SOD, CAT, GPX and GSH were significantly lower in these groups when compared with the control rats in the kidney and testis tissue. AG treatment significantly decreased MDA, TOS and OSI levels and increased SOD, CAT, GPX and GSH levels, when compared to the RT-treated groups in both kidney and testis tissue. BUN and Cr levels did not change among the groups, whereas testosterone levels were found as reduced in the RT-treated rats. AG treatment significantly augmented these hazardous effects of RT on testis tissue. According to our results, AG has beneficial effects against RT-induced kidney and testis injury.

Melatonin, quercetin and resveratrol attenuates oxidative hepatocellular injury in streptozotocin-induced diabetic rats.

In this study, effects of melatonin, quercetin and resveratrol on hepatocellular injury in streptozotocin (STZ)-induced experimental diabetes were aimed to be investigated by histological and biochemical methods. Thirty-five male Wistar albino rats were divided into five groups, namely, control, diabetes (STZ 45 mg/kg/single dose/intraperitoneally (ip)), diabetes + melatonin (10 mg/kg/30 days/ip), diabetes + quercetin (25 mg/kg/30 days/ip) and diabetes + resveratrol (10 mg/kg/30 days/ip). Initial and final blood glucose levels and body weights (BWs) were measured. At the end of the experimentation, following routine tissue processing procedure, sections were stained with haematoxylin-eosin (H-E), periodic acid Schiff and Masson's trichrome. Tissue malondialdehyde (MDA) and glutathione (GSH) levels and superoxide dismutase (SOD) and catalase (CAT) activities were examined. The diabetic rats had significantly higher blood glucose levels than those of control rats (p = 0.0001). Mean BWs of diabetic rats were significantly decreased when compared with the control rats (p = 0.0013). Histopathological alterations including cellular glycogen depletion, congestion, sinusoidal dilatation, inflammation and fibrosis were detected in diabetes group. On the other hand, histopathological changes markedly reduced in all of the treatment groups (p = 0.001). Mean tissue MDA level was increased but mean tissue CAT and SOD activities and GSH levels were decreased in the diabetes group. Melatonin, quercetin and resveratrol administered diabetic rats showed an increase in CAT activities and GSH levels and a decrease in MDA levels (p < 0.05, for all). Melatonin, quercetin and resveratrol administrations markedly reduced hepatocellular injury in STZ-induced experimental diabetes.

Preventive and early therapeutic effects of ß-glucan on the bleomycin-induced lung fibrosis in rats.

OBJECTIVE: The ß-glucans are long-chain polymers of glucose, which comprise the fungal cell wall, stimulate cells of the innate immune system, enhance disturbed epithelization, and have antioxidant effects. Oxidative stress has been implicated in the pathogenesis of bleomycin-induced lung fibrosis and various antioxidant agents have been studied for prevention and treatment of the disease. In this experimental animal study, we assessed effects of ß-glucan, extracted from barley, on the bleomycin-induced lung fibrosis, and evaluated differences of starting before and after bleomycin instillation. MATERIALS AND METHODS: Male Spraque-Dawley rats were given a single dose of bleomycin in pulmonary fibrosis groups. First dose of ß-glucan and NAC was given three days before the bleomycin injection, and at one of the other group ß-glucan was started 12 hours after bleomycin and continued until 14th day. Fibrotic changes in lung were estimated by using Aschoft's criteria and measuring lung hydroxyproline content. RESULTS: Bleomycin induced severe pulmonary fibrosis with marked increase in hydroxyproline content of lung tissue and typical lung fibrosis, which was prevented by ß-glucan. Hydroxyproline level was significantly higher in bleomycin treated rats than the other groups, and its level was decreased in the therapeutic groups, especially in the ß-glucan post-bleomycin group fibrosis score, hydroxyproline and MDA levels returned to the control levels. On the other hand, reduced glutathione level elevated in the same group. CONCLUSIONS: The data suggest that ß-glucans have protective and early therapeutic effects against bleomycin-induced lung fibrosis in rats.

Resveratrol successfully treats experimental endometriosis through modulation of oxidative stress and lipid peroxidation.

BACKGROUND AND AIMS: The purpose of this study was to investigate the potential therapeutic efficiency of resveratrol in the treatment of experimental endometriosis in rats. SETTINGS AND DESIGN: Experimental study was carried out in a University hospital. MATERIALS AND METHODS: Endometriosis was surgically induced in 24 female rats. Four weeks after this procedure, the viability and dimensions of the endometriosis foci were recorded. Rats were then randomly divided into three groups: (1) Control group (n = 8); (2) low dose (10 mg/kg) resveratrol group (n = 8); (3) high dose (100 mg/kg) resveratrol group (n = 8). At the end of the 7-day treatment, blood samples were taken and laparotomy was performed. The endometrial implants were processed for biochemical, histological and immunohistochemical studies. STATISTICAL ANALYSIS USED: The Kruskal-Wallis H test and one-way ANOVA test were used. RESULTS: Resveratrol-treated rats showed significantly reduced endometriotic implant volumes (P = 0.004). After treatment, a significant and dose-dependent increase in activities of superoxide dismutase and glutathione peroxidase in serum and tissue of the rats in Group 2 and Group 3 was detected. Similarly, serum and tissue malonyl dialdehyde levels and tissue catalase levels were significantly higher in Group 3 than that of control animals. Histological scores and proliferating cell nuclear antigen expression levels were also significantly reduced in Group 2 and Group 3 than that of control group. CONCLUSION: In a rat endometriosis model, resveratrol showed potential ameliorative effects on endometriotic implants probably due to its potent antioxidative properties.