Exogenous Apelin-13 Administration Ameliorates Cyclophosphamide- Induced Oxidative Stress, Inflammation, and Apoptosis in Rat Lungs.

BACKGROUND: Apelin-13 is an endogenous adipocytokine known for its antioxidant, antiinflammatory, and antiapoptotic properties. OBJECTIVE: We aimed to investigate the possible protective effects of exogenous Apelin-13 administration on oxidative stress, inflammation, and apoptosis induced by the cytotoxic agent cyclophosphamide (CP) in the lungs. METHODS: Twenty-four male Wistar albino rats were divided into four groups: Control (saline), CP (200 mg/kg), Apelin-13 (10 µg/kg/day), and CP+Apelin-13. CP was administered as a single dose on the fifth day, and apelin-13 was administered intraperitoneally for five days. Total oxidant status (TOS), total antioxidant status (TAS), and lipid peroxidation were determined with spectrophotometry, TNFα and IL1ß were determined with ELISA, APJ, Sirt1, NF-κB, and p53 mRNA expressions were determined with qRT-PCR, cytochrome (Cyt) C and caspase-3 protein expressions were studied with western blotting in lung tissues. The oxidative stress index (OSI) was also calculated. Furthermore, serum surfactant protein-D (SP-D) and Krebs von den Lungen-6 (KL-6) levels were measured with ELISA. RESULTS: Compared to the control group, TOS, OSI, lipid peroxidation, TNFα, IL1ß, cyt C, caspase-3, APJ, NF-κB, and p53 were higher, and Sirt1 was lower in the lung tissue of rats in the CP group. Serum KL-6 and SP-D levels were higher in the CP group. Co-administration of CP with Apelin-13 completely reversed the changes induced by CP administration. CONCLUSION: Exogenous Apelin-13 treatment protected lung tissue against injury by inhibiting cyclophosphamide-induced oxidative stress, inflammation, and apoptosis. This protective effect of apelin-13 was accompanied by upregulation of the Sirt1 and downregulation of NF-κB/p53 in the lungs.

The Effects of Curcumin on Mechanical Functions and Cardiac Contractility in Isolated Rat Hearts.

OBJECTIVE: Curcumin is a bioactive compound that has well-known pharmacological activities. Numerous studies have shown that curcumin provides potential cardiovascular benefits through a variety of mechanisms.The present study aims to discuss different concentrations of curcumin's impact on mechanical functions and cardiac contractility in isolated perfused rat hearts. METHODS: The hearts were isolated under sodium thiopental (50 mg/kg) anesthesia and perfused with a modified Krebs-Henseleit solution (mK-Hs). After stabilization, curcumin was applied in concentrations of 0.1, 1, and 10 µM. In isolated rat hearts, indexes of + dP / dt max, LVDP, MAP, and LVEDP were evaluated for cardiac contractility and ventricular function. RESULTS: All curcumin concentrations reduced +dP/dtmax and LVDP. Ten µM curcumin also significantly decreased heart rate. Curcumin (1 and 10 µM) increased LVEDP and reduced MAP amplitude with a concomitant increase in MAP duration. Curcumin at all concentrations did not affect dMAPdtmax and dMAPdtmin. CONCLUSION: Our results might suggest that curcumin at higher concentrations (≥ 1 µM) increases LVEDP with a negative chronotropic effect and decreases MAP amplitude with an increase in MAP duration. There is sufficient evidence from this study that Curcumin possesses an adverse inotropic action. Different disease models should support the pathophysiological role of Curcumin on cardiac contraction.

Effects of curcumin and melatonin treatment in the cerebral cortex of adult rats.

The study investigated the effect of exogenous melatonin and (or) curcumin treatment on the cerebral cortex of adult rats. In this context, malondialdehyde (MDA), nitric oxide (NO), glutathione (GSH), superoxide dismutase (SOD), nuclear factor E2-related factor 2 (Nrf2) and SIRT2 protein expression were examined. A total of 30 Wistar albino rats involved in the study were randomly divided into five groups. Over 30 days, the control groups received phosphate-buffered saline or dimethyl sulfoxide injections, and the treatment groups received melatonin, curcumin, or a combination of melatonin and curcumin injections. In the cerebral cortex homogenates, the MDA, GSH, and sum of NO were respectively determined by the thiobarbituric acid, modified Ellman and Griess test methods. The SOD and Nrf2 levels were examined using the ELISA method and SIRT2 protein expression using the Western blot technique. The study found that both melatonin and curcumin treatments significantly reduced lipid peroxidation and SIRT2 protein expression levels (p < 0.05) and increased the Nrf2 level in the cytoplasm (p < 0.05). The study revealed that curcumin and melatonin treatments reduced MDA and SIRT2 protein expression level and increased intracellular Nrf2, GSH, and SOD in the cortex tissue. We also found that the combined melatonin and curcumin treatment produced no synergistic effect.

Effect of Skiing on Physical Performance, Pain, and Quality of Life Based on Gender.

CONTEXT: Identifying gender-specific differentiation in each sport type is significant. In this way, sport- and gender-specific gains can be predicted. Therefore, this study aimed to examine the effects of skiing on physical performance, pain, quality of life, and gender-based differentiation. DESIGN: Crossover trial. METHODS: Sixty-eight volunteers, between 18 and 25 years of age, with no history of severe trauma in the spine and extremities, participated in our study. The skiers group consisted of licensed athletes (17 males and 17 females) who did active skiing for at least the past 2 years, the control group consisted of nonathletic and age-matched participants with no skiing experience (17 males and 17 females). Step test, vertical jump test, Flamingo balance test, hand-grip strength, and back-leg-chest strength measurements were performed to evaluate physical performance. Visual Analog Scale, McGill Pain Questionnaire, and Oswestry Low Back Pain Disability Questionnaire were used to evaluate pain experience. Quality of life was evaluated with Short Form-36 (SF-36). RESULTS: Compared to the sedentary controls, VAS-activity and Oswestry Disability Index scores were lower; and aerobic performance, balance, hand-grip strength, back-leg-chest strength, and quality of life (SF-36-general health, SF-36-vitality, SF-36-mental health, and SF-total score) were higher in skiers. Skiing was found to be effective in eliminating gender-based differentiation of the variables of hand-grip strength, pain, and quality of life; however, back-leg-chest strength and anaerobic performance variables were found to be ineffective in eliminating gender differentiation. CONCLUSIONS: Skiing allows that the individual increases physical performance and quality of life. It can also minimize gender-based differentiation of certain variables, such as muscular force, pain, and quality of life.

SIRT2 and FOXO3a expressions in the cerebral cortex and hippocampus of young and aged male rats: antioxidant and anti-apoptotic effects of melatonin.

Melatonin has antioxidant, anti-apoptotic and anti-aging effects in the brain. Sirtuin2 (SIRT2) accumulates in the central nervous system with aging, and its inhibition appears to be protective in aging and aging-related neurodegenerative diseases. Forkhead Box-class O3a (FOXO3a) transcription factor is one of the main targets of SIRT2, and SIRT2-mediated FOXO3a deacetylation is closely related to aging, oxidative stress, and apoptosis. This study aimed to investigate the effects of melatonin on SIRT2 and FOXO3a expressions in the cerebral cortex and hippocampus of aged rats. Young (3 months, n = 18) and aged (22 months, n = 18) male Wistar rats were divided into control (4% DMSO-PBS, sc, for 21 days), melatonin (10 mg/kg, sc, for 21 days) and salermide (1 mM; 25 µl/100 g bw, ip, for 21 days) groups. SIRT2, FOXO3a, Bcl-2, Bax and Bim expressions in the cerebral cortex and hippocampus were demonstrated by Western blotting. SIRT2 and FOXO3a protein levels were also measured by a sandwich ELISA method. Oxidative stress index (OSI) was calculated by measuring total oxidant status (TOS) and total antioxidant status (TAS). Aging increased SIRT2, FOXO3a, Bim (only in the cerebral cortex), Bax (only in the hippocampus), TOS, and OSI, while decreasing Bcl-2, Bcl-2/Bax and TAS in both brain regions. Melatonin decreased SIRT2, FOXO3a, oxidative stress parameters and pro-apoptotic proteins, while increasing TAS, Bcl-2 and Bcl-2/Bax, more specifically in the hippocampus of the aged brain. Our results indicate that inhibition of SIRT2 and FOXO3a expressions appears to be involved in the protective effects of melatonin in the hippocampus of aged rats.

The significance of blood and salivary oxidative stress markers and chemerin in gestational diabetes mellitus.

OBJECTIVE: Gestational diabetes mellitus (GDM) is a medical complication of pregnancy. The aim of this study was to evaluate the correlations between the salivary and blood levels of oxidative stress markers and an adipokine chemerin, which play a role in the pathogenesis of GDM. MATERIALS AND METHODS: Study groups (Control (n = 29), GDM (n = 22)) had been assessed clinically healthy oral hygiene, according to the age range between 25 and 40 years, BMI<30 kg/m2, who were non-smokers and who were not having systemic diseases. GDM was diagnosed using a 100 g OGTT. Saliva samples were collected without stimulation between 08.30 and 10.00 a.m.. Chemerin and TrxR levels were measured by ELISA. Malondialdehyde, sulfhydryl and NO levels were determined by spectrophotometric analysis. Statistical analysis were performed by Shapiro Wilk, Mann Whitney U, Student's t test. RESULTS: Blood pressure, BMI, and plasma chemerin, salivary chemerin, fasting glucose, LDL, triglyceride, CRP levels in GDM were not different when compared to Control. There were significant differences between Plasma TrxR and HDL levels. Also, significant differences between salivary TrxR and Malondialdehyde levels were observed in GDM. CONCLUSION: It was concluded that the optimal cut-off points for oxidative stress parameters and chemerin level can be used to distinguish between healthy pregnant and GDM.

The protective role of melatonin and curcumin in the testis of young and aged rats.

We aimed to investigate the effect of melatonin and curcumin treatment on oxidative stress, apoptosis, and histology of testicular tissue in our study. Four groups were formed using young (4 months old, n = 6) and aged (20-22 months old, n = 18) male Wistar albino rats: (a) Young control (1% ethanol:phosphate-buffered saline [PBS], subcutaneously [s.c.]); (b) Aged control (CTL; n = 6, 1% ethanol:PBS, s.c.); (c) Aged Melatonin (MLT; n = 6, 10 mg/kg, s.c.); (d) Aged Curcumin (CUR; n = 6, 30 mg/kg, i.p.). At the end of 21 days, the rats were sacrificed, and testicular tissues were removed. Malondialdehyde (MDA) in the testicular tissue was determined with thiobarbituric acid reactive substances formation, and glutathione (GSH) was determined with modified Ellman method; testosterone level was determined with chemiluminescence method and histologic changes were determined with Haematoxylin-Eosin and Johnsen's scoring; Apoptotic cell counts were made with TUNEL staining of seminiferous tubule in testis. With ageing, MDA level increased in testicular tissue, but GSH and blood testosterone levels decreased. Melatonin treatment for aged rats significantly decreased Paired total testicular/body weight ratio compared to aged control group (p < 0.05). Curcumin treatment for aged rats significantly increased GSH level compared to the aged control group (p < 0.05). Besides, melatonin and curcumin treatment significantly decreased the number of apoptotic cells and significantly increased Johnsen's score (p < 0.05).

The effects of melatonin and curcumin on the expression of SIRT2, Bcl-2 and Bax in the hippocampus of adult rats.

OBJECTIVE: Though the mechanisms are not clearly understood, melatonin and curcumin have been reported to have neuroprotective effects. However, the mechanisms of neuroprotective effects of melatonin and curcumin in the brain are not clearly understood. In the current study, we investigated the effects of melatonin and curcumin treatments on oxidative stress parameters, the expression of SIRT2, Bcl-2 and Bax in the hippocampus. METHODS: A total of thirty adult (13 months-old) male Wistar rats were divided into five groups: Control (1% ethanol:PBS), s.c. for 30 days), dimethyl sulfoxide (10%, s.c. for 30 days), Melatonin (10 mg/kg/day, s.c. for 30 days), Curcumin (30 mg/kg/day, i.p. for 30 days) and Salermide (100 µM, i.p. for 30 days). The levels of malondialdehyde (MDA) glutathione (GSH) were measured as oxidative stress parameters in the hippocampus. The expression levels of SIRT2, Bcl-2 and Bax proteins were tested by western blotting and the SIRT2 protein levels of the hippocampal region was measured by a sandwich ELISA method. RESULTS: Melatonin and curcumin significantly decreased MDA and SIRT2 expression in the hippocampus (p < 0.05). Accordingly, a significant increase in the GSH levels of curcumin-treated group and melatonin-treated group was observed. Melatonin, but not curcumin, significantly increased the Bcl-2 expression of the hippocampal region. There was a significant correlation between SIRT2 and MDA levels (p < 0.05). DISCUSSION: In conclusion, our results suggest that melatonin may increase cell survival in the hippocampus via decreasing oxidative stress and SIRT2 expression and increasing Bcl-2 expression.