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Reproduction is characterized by a series of massive renovations at molecular, cellular, and tissue levels. Recent studies have strongly tended to reveal the involvement of basic molecular pathways such as autophagy, a highly conserved eukaryotic cellular recycling, during reproductive processes. This review comprehensively describes the current knowledge, updated to September 2022, of autophagy contribution during reproductive processes in males including spermatogenesis, sperm motility and viability, and male sex hormones and females including germ cells and oocytes viability, ovulation, implantation, fertilization, and female sex hormones. Furthermore, the consequences of disruption in autophagic flux on the reproductive disorders including oligospermia, azoospermia, asthenozoospermia, teratozoospermia, globozoospermia, premature ovarian insufficiency, polycystic ovarian syndrome, endometriosis, and other disorders related to infertility are discussed as well. Abbreviations: AKT/protein kinase B: AKT serine/threonine kinase; AMPK: AMP-activated protein kinase; ATG: autophagy related; E2: estrogen; EDs: endocrine disruptors; ER: endoplasmic reticulum; FSH: follicle stimulating hormone; FOX: forkhead box; GCs: granulosa cells; HIF: hypoxia inducible factor; IVF: in vitro fertilization; IVM: in vitro maturation; LCs: Leydig cells; LDs: lipid droplets; LH: luteinizing hormone; LRWD1: leucine rich repeats and WD repeat domain containing 1; MAP1LC3: microtubule associated protein 1 light chain 3; MAPK: mitogen-activated protein kinase; MTOR: mechanistic target of rapamycin kinase; NFKB/NF-kB: nuclear factor kappa B; P4: progesterone; PCOS: polycystic ovarian syndrome; PDLIM1: PDZ and LIM domain 1; PI3K: phosphoinositide 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate; PtdIns3K: class III phosphatidylinositol 3-kinase; POI: premature ovarian insufficiency; ROS: reactive oxygen species; SCs: Sertoli cells; SQSTM1/p62: sequestosome 1; TSGA10: testis specific 10; TST: testosterone; VCP: vasolin containing protein. [ABSTRACT FROM AUTHOR]

Background: Diabetes has become an important health problem in the world. Natural agents, with antidiabetic property, are potential candidates for improving diabetes. Urtica Dioica Distillate (UDD) or Araghe Gazaneh is widely used for the treatment of diabetes as per traditional medicine. Despite the tremendous use of UDD as an antidiabetic compound in folk medicine, the antidiabetic effects of UDD has been neglected by medical scientists. In this study, we aimed to evaluate the effects of UDD on the glucose metabolism in diabetic rats. Methods: A total of 24 male rats were divided equally into four groups, two treatment and two control groups, each containing normal or Streptozotocin (STZ)-induced diabetic rats. During 4 weeks, control and treatment rats received water or UDD, respectively. Fasting blood sugar (FBS), HbA1c, serum creatinine, blood urea nitrogen, and specific activities of hepatic enzymes including glucokinase (GK), hexokinase (HK), glucose-6-phosphate dehydrogenase (G6PD), and muscle glucose transporter type 4 (GLUT4) and liver phosphoenolpyruvate carboxykinase (PEPCK) mRNA levels were measured. Results: FBS and HbA1c increased in diabetic groups. Treatment with UDD significantly lowered FBS and prevented weight loss. Decreased FBS level was associated with higher activity levels of GK and HK in UDD-treated diabetic rats. G6PD-specific activity decreased in diabetic control rats compared to nondiabetic ones, but UDD treatment improved it to the normal levels. A significant decrease in the expression level of GLUT4 was observed in diabetic control rats compared to nondiabetic ones, but UDD increased it to the normal levels. Conclusions: These findings suggest that UDD might exert therapeutic effects against diabetes by improving glucose metabolism and can be used as an alternative or complementary medicine for the treatment of diabetic patients. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis is a bone disease leading to bone fracture and affects 200 million women worldwide. Autophagy and apoptosis are two fundamental mechanisms that are involved in the development of osteoporosis. In this study we aim to investigate the combined effects of quercetin and alendronate on the markers of osteoporosis, autophagy, and apoptosis in the bone of ovariectomized rats. Methods and results: Fifty adult female Sprague–Dawley rats were ovariectomized and treated with alendronate alone (5 µg/kg/day) or alendronate (5 µg/kg/day) in combination with quercetin (15 mg/kg/day) for 12 weeks. Then, ELISA, stereological tests, Real-time PCR analysis, and immunofluorescence assay were used to measure the markers of osteoporosis, autophagy, and apoptosis in the serum and tibia of rats. The serum osteocalcin was significantly decreased in ovariectomized rats that received quercetin and alendronate compared with alendronate only. Stereological data showed that except for osteoclasts, the total trabecular volume, bone weight, bone volume, osteocyte, and osteoblast numbers were increased in an ovariectomized group that was treated with quercetin and alendronate compared with alendronate alone. Except for Bcl2, the autophagy markers (Beclin-1 and LC3B) and Caspase-3 were significantly downregulated in ovariectomized rats that received quercetin and alendronate compared with those treated with alendronate alone. Conclusion: Our results show that quercetin enhances the anti-osteoporotic effects of alendronate, possibly through the regulation of autophagy and apoptosis mechanisms. These findings suggest that the combination of quercetin and alendronate could be a useful therapeutic strategy in the treatment of osteoporosis in postmenopausal women. [ABSTRACT FROM AUTHOR]

The present study is the first attempt made to investigate the effects of diabetes on expression and promoter DNA methylation of TGF-β1, ESR-1, and CDH-1 genes and also the effects of folic acid (FA) and vitamin E (Vit E) supplementations on improving diabetes mellitus. STZ-induced diabetic rats were treated with Vit E (200 mg/kg/day) and FA (25 mg/kg/day) for 8 weeks and expression and DNA methylation of TGF-β1, ESR-1, and CDH-1 genes in uterus were analysed. Data indicated that diabetes increases the expression of TGFβ-1 and ESR-1 and decreases CDH-1 expression and TGFβ-1 promoter methylation in the uterus of rats. Vit E and FA improved the negative effects of diabetes by decreasing the expression of TGFβ-1 and ESR-1 and increasing that of CDH-1 in diabetic rats. In conclusion, these findings emphasise that Vit E and FA supplementations could improve negative effects caused by diabetes on uterus function and fertility in diabetic rats. [ABSTRACT FROM AUTHOR]

To assess the effect of sequential treatment with Vitamin C (VC) and Quercetin (Q) on Nrf2-related oxidative stress in PC3 and DU145 cells, viability was measured by MTT assay. Intracellular ROS levels were determined, using 2'-7'-dichlorodihydrofluorescein diacetate fluorescent as a probe. Nrf2 gene expression was investigated by quantitative reverse transcription polymerase chain reaction, and Nrf2 protein levels were defined by western blot analysis. The activity of glutathione peroxidase (GPx), glutathione reductase (GR), nicotinamide adenine dinucleotide phosphate dehydrogenase quinone 1 (NQO1) and hemeoxygenase 1 (HO-1) enzymes were measured. The IC50 values for VC + Q were 263.03–372.1 µM and 144.2–194.1 µM respectively and 200 µM VC + 50 µM Q (dose no.1) and 100 µM VC + 75 µM Q (dose no.2) were selected. Sequential treatment of PC3 cells led to a significant reduction of Nrf2 mRNA expression and protein levels in addition to a significant reduction of GPx, GR and NQO1 enzymatic activity. Although the data was slightly different for DU145 cells after the treatments, in terms of Nrf2 gene expression, we obtained the same results. Our study revealed the significant effects of sequential treatment with VC + Q on Nrf2 suppression in prostate cancer cells. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD) is one of the most important liver diseases. High-density lipoprotein (HDL) has anti-atherogenic properties and its reduction can be associated with fatty liver. Serum ferritin levels are usually elevated in patients with NAFLD. This study aimed to evaluate the correlation between HDL subtypes and serum ferritin levels with evidence of NAFLD in liver histology of organ donors.Methods: One hundred organ donor patients who were eligible for the study were included in the study and ferritin; HDL2 and HDL3 were measured in blood samples. Donated liver tissue biopsy specimens were evaluated for fatty liver and NAFLD activity score (NAS). In addition, AST and ALT were measured in recipients 24 h after transplant. All data abstracted and analyzed statistically.Results: Serum HDL2 levels and HDL2/HDL3 ratio in patients with NAS > 1 were significantly lower (P < 0.05). Serum levels of HDL3 and ferritin were not significantly associated with NAS >1 (P > 0.05). In addition, serum ferritin > 1000 ng/ml in organ donors associated with increased AST and ALT levels 24 h after transplantation in the liver organ recipient.Conclusions: Lower HDL2 values and HDL2/HDL3 ratio were associated with increased NAFLD activity score, but HDL3 and ferritin did not show such a relationship. In addition, higher levels of ferritin in organ donors may be associated with increased AST and ALT 24 h after liver transplantation in the organ recipient. [ABSTRACT FROM AUTHOR]

Introduction: Nowadays, the prevalence of nicotine abuse among women has increased dramatically. In the current study, we aimed to investigate the effect of nicotine exposure on breast MCF-7 and ovarian OVCAR-3 cell lines for assessing the toxicity of nicotine in the cells of these organs. Methods: The MCF-7 and OVCAR-3 cells were treated with increasing nicotine concentrations ranging from 0 (control), 10-11, 10-8 and 10-6 M for 24h. Effect of nicotine treatments on major antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), cellular levels of glutathione (GSH) and malondialdehyde (MDA) were monitored. Results: We showed that the CAT activity in MCF-7 cells increased only at 10-6 M dose of nicotine. The GPx and GR activity was decreased at 10-8 and 10-6 M of nicotine in MCF-7 cells, but in OVCAR-3 cells, this decrease was significant only at 10-6 M dose of nicotine. Reduced GSH decrease was statistically significant only at 10-8 and 10-6 M of nicotine in MCF-7 cells; otherwise, in OVCAR-3 cells, this decline was significant only at 10-6 M of nicotine. Nicotine at 10-8 and 10-6 M concentration caused a significant increase in MDA levels in MCF-7 cells. Conclusion: This study showed that breast MCF-7 cells are more vulnerable than ovarian OVCAR-3 cells against nicotine-induced oxidative toxicity. [ABSTRACT FROM AUTHOR]

Copyright of Gynecological Endocrinology is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: Hyperglycemia is a severe consequence of diabetes mellitus (DM). Throughinduction of oxidative stress, it plays a major role in the pathogenesis of several complications in DM. Therefore, new strategies and antioxidants should be implemented inthe treatment of DM. Quercetin is a flavonoid with strong antioxidant capacity found dominantly in vegetables, fruits, leaves, and grains. The current study aimed to investigate quercetin protective effects under D-glucose-induced oxidative stress by assessing antioxidant defense enzymes inHepG2 cells as an in vitro model. Materials and Methods: HepG2 cells were cultured with different concentrations of D-glucose (5.5, 30 and 50 mM) and/or 25 µM quercetin for 48 and 72 hr, respectively. The effect of treatments on cellular integrity, antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) activity, andcellular levels of glutathione (GSH) and malondialdehyde (MDA) wasdetermined. Results: D-glucose had various effects on intracellular antioxidant defense atdifferent doses and time-points and quercetin could attenuate oxidative stress and modulate antioxidant defenses. Conclusion: The results of this study indicated that flavonoid quercetin could be proposed as an agent protecting hepatic HepG2 cells against oxidative stress associated with hyperglycemia. [ABSTRACT FROM AUTHOR]

Osteoporosis is the most prevalent metabolic bone disease and one of the most important postmenopausal consequences. The aim of this study was to investigate the effects of quercetin (Q) and vitamin E (vitE) on ovariectomy‐induced osteoporosis. Animals were ovariectomized and treated with Q (15 mg/kg/day), vitE (60 mg/kg/day), estradiol (10 µg/kg/day), and Q (7.5 mg/kg/day) + vitE (30 mg/kg/day) for 10 weeks by gavage, and osteoporosis markers and messenger RNA (mRNA) expression of autophagy and apoptosis‐related genes were analyzed in serum and tibia of rats. Data indicated that ovariectomy resulted in development of osteoporosis as demonstrated by reduction in serum calcium, bone weight, bone volume, trabeculae volume, and the total number of osteocytes and osteoblasts, and increase in the total number of osteoclasts and serum osteocalcin. Total mRNA expressions of LC3, beclin1, and caspase 3 were also increased and bcl2 expression was decreased in the tibia. By reversing these changes, treatment with Q and vitE markedly improved osteoporosis. In conclusion, Q, and to a lesser extent, vitE, prevented osteoporosis by regulating the total number of bone cells, maybe through regulating autophagy and apoptosis. [ABSTRACT FROM AUTHOR]

Endometriosis, as the leading cause of infertility, is attributed to oxidative stress, inflammation, and autophagy dysregulation. This study was conducted to evaluate the effect of quercetin and metformin, alone or in combination, on the ectopic and eutopic endometrial tissues in a rat model of endometriosis. We divided 60 female rats into 6 groups, including SH, Endo, Endo + Oil, Endo + Q, Endo + M, and Endo + Q + M. The last five groups underwent a surgery, so that we could induce endometriosis, and after 4 weeks, daily treatment began, lasting for a month. Subsequently, the size and histoarchitecture of the endometrial implants, serum levels of 17β-estradiol, progesterone and tumor necrosis factor (TNF)-α, and markers of oxidative stress and autophagy were assessed utilizing ELISA and gene expression analysis. Our results shed light to the fact that serum TNF-α and 17β-estradiol levels significantly increased in endometriosis rats. Moreover, NADPH: quinone oxidoreductase (NQO1) enzyme activity and gene expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and autophagy markers significantly decreased; meanwhile, mammalian target of rapamycin (mTOR) gene expression increased in the ectopic endometrial tissues, as compared with eutopic ones. Surprisingly, our results demonstrated that the treatment in which we applied the combination of quercetin and metformin significantly reversed these changes and had a pronounced effect on the endometrial implant size and gene expression levels of mTOR and autophagy markers in ectopic endometrium. The findings of the present study suggest that quercetin, metformin, and their combination were of potential therapeutic effects on the rat model of endometriosis. [ABSTRACT FROM AUTHOR]

Copyright of Gynecological Endocrinology is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aim: Maternal diabetes adversely retards the development of preimplantation embryos. Quercetin is a flavonoid belonging to phytoestrogens family and may be useful in treatment of reproductive disorders. The aim of this study was investigation of the ameliorative effects of quercetin administration on preimplantation embryo development in diabetic pregnancy. Methods: Diabetic and healthy female mice were treated with 30 mg/kg/day quercetin 4 weeks before conception. Blastocysts were recovered at the 4th day of pregnancy for protein and mRNA expression changes. Plasma sex‐steroid levels were also analyzed. Results: Quercetin significantly decreased blood glucose levels in diabetic mice. Embryos retrieved from diabetic mice exhibited a considerable delay in morphological development. In diabetic mice with quercetin treatment, morphological distribution was shifted considerably to the well‐developed stages. Serum estradiol level reduced in diabetic mice but, treatment with quercetin significantly increased serum estradiol level. While IGF1R, integrin αvβ3, and Cox2 mRNA expression in the blastocyst of diabetic mice decreased significantly, quercetin treatment caused increasing expression levels of these genes. Expression of the Caspase3 gene increased dramatically in the collected blastocysts from diabetic mice and reduced following quercetin treatment. Besides, the inactive β‐catenin protein level in the blastocysts of diabetic mice was higher than that in normal mice, while treatment with quercetin decreased the level of inactive β‐catenin protein in the blastocyst of diabetic mice. Conclusion: Quercetin protects preimplantation embryos from destructive effects of diabetes. The amelioration of sex hormones disturbance in early pregnancy may help to treat reproductive disorders in diabetic women. Quercetin can be considered as a novel solution to the improvement of reproductive disorders in the diabetic females. [ABSTRACT FROM AUTHOR]

The exact mechanisms of polycystic ovary syndrome (PCOS) are unknown and there is no effective cure for the disease. The aim of this study was to evaluate the alterations in serum oestradiol and adiponectin levels and in the expression of some important genes in the uterine and ovarian tissues of PCOS rats. The therapeutic effect of quercetin on PCOS was also assessed. Rats were divided into five groups: control, ethanol, quercetin (Q), PCOS and PCOS+Q. After 30 days of oral treatments, the rats' ovaries and uteri were removed and nesfatin-1, aromatase and adipoR1 expressions were quantified with real-time polymerase chain reaction. Serum adiponectin and oestradiol levels were evaluated using enzyme-linked immunosorbent assay technique. The results of this study showed that expression of nesfatin-1 and adipoR1 genes and adiponectin serum levels decreased in the PCOS rats, but aromatase expression and oestradiol level increased. Treatment with quercetin increased the adiponectin level and expression of adipoR1 and nesfatin-1 and decreased both the expression of aromatase and the oestradiol level. Quercetin improved PCOS by phytoestrogenic effects and mimicking oestrogen's function. Quercetin also affects important factors in both the uterus and ovary and could improve the obesity and the diabetic and infertility symptoms of PCOS. Quercetin could improve polycystic ovary syndrome (PCOS) by its phytoestrogenic effects, mimicking oestrogen's function. Also, quercetin affects obesity and diabetes factors such as adiponectin, nesfatin-1 and adiponectin receptor, thus improving the symptoms of PCOS. Quercetin significantly decreased oestrogen levels and might help fertility problems in PCOS patients. [ABSTRACT FROM AUTHOR]

Background: There is increasing evidence indicating an incidence of infertility and also the risk of endometrial cancers among smokers. However, the mechanism underlying nicotine adverse effect on female reproduction remains unclear. Growing evidence has suggested that environmental exposures such as nicotine could modulate the epigenome. No study has yet been published to evaluate the direct effect of nicotine on the epigenome profiling of human endometrial stromal cells (HESC). Herein, we decided to examine the direct effects of nicotine on global genomic DNA methylation status and DNA methyl- transferases (DNMTs) gene expression in HESC. HESC were treated with different doses of nicotine (0 or control, 10− 11, 10− 8 and 10− 6) M for 24 h and their genomic global DNA methylation and gene expression of DNMTs (DNMT1, DNMT3A, and DNMT3B) were investigated using ELISA and real-time PCR, respectively. Results: Nicotine treatments reduced the average level of DNMTs gene expression by 90, 79, and 73.4% in 10− 11, 10− 8 and 10− 6 M of nicotine treated cells as compared to control cells, respectively (p < 0.05). Also, 10− 8 and 10− 6 M of nicotine concentrations effectively reduced the amounts of 5-methylated cytosine (5-mC) by 1.09 and 1.87% compared to control cells, respectively (p < 0.05). The 5-mC percentages were positively correlated with the relative cellular DNMTs expression in HESC as verified by the Pearson correlation test. Conclusion: An interesting possibility raised by the current study is that the reduced genomic global DNA methylation level in HESC may be partly due to the suppression of DNMTs gene expression caused by nicotine in these cells. [ABSTRACT FROM AUTHOR]

Estrogen deficiency after menopause accelerates redox imbalance, leading to oxidative stress (OS) and other postmenopausal complications such as osteoporosis and cardiovascular disease. In the present study, the effects of quercetin (Q), vitamin E (vitE) and estradiol (E2) on the oxidative status in ovariectomized (OVX) rats were investigated. OVX animals were treated with Q (15 mg/kg/day), vitE (60 mg/kg/day), E2 (10 μg/kg/day) and Q (7.5 mg/kg/day)+vitE (30 mg/ kg/day) for 10 weeks. OS markers were analyzed in the serum and tibia of rats. Data indicated that after ovariectomy, rats exhibited a reduction in serum and tibia antioxidants and elevation of oxidant markers. The activities of antioxidant enzymes (AOEs), glutathione peroxidase (GPx), catalase (CAT) and glutathione reductase were decreased and the glutathione (GSH) content was reduced, whereas the malondialdehyde (MDA) level was increased. Treatment with Q, vitE and E2 markedly reversed these changes and improved OS. In conclusion, prevention by antioxidant agents, including Q and vitE, could be a potential approach in the management of menopause-related complications. [ABSTRACT FROM AUTHOR]

Nicotine is a major component of tobacco plants and is responsible for the development of reproductive problems in smokers. Nicotine has been recognized to result in oxidative stress by inducing the generation of reactive oxygen species (ROS) in some parts of female reproductive system, but the effect of nicotine on endometrium that plays an important role in reproductive biology stays unexplored. The aim of this work was to clarify the direct effects of nicotine administration on the antioxidant defense system and lipid peroxidation in human endometrial cells. Human endometrial stromal primary cells were treated with nicotine (0, 10−11, 10−8, and 10−6 M) for 24 hours. On nicotine administration, the endometrial cells were associated with a decrease in antioxidant defense markers such as Glutathione (GSH) level, glutathione peroxidase (GPx), glutathione reductase (GR), and catalase (CAT) enzymes activity and higher levels of malondialdehyde (MDA) in a dose-dependent manner when compared to the control. We concluded that nicotine as a pro-oxidant affects the oxidative state of the endometrial cells. [ABSTRACT FROM AUTHOR]

Insulin resistance (IR) and infertility are two major complications of polycystic ovary syndrome (PCOS), which are the results of changes in certain parts of the reproductive and metabolic systems. We aimed to observe the effect of quercetin on dehydroepiandrosterone (DHEA)-induced PCOS and insulin resistance in rats. All animals were divided into five groups and DHEA was used to induce PCOS. Bodyweight and ovarian morphology of all groups were observed. Fasting blood glucose and insulin levels were analysed. The homeostasis model assessment of insulin resistance (HOMA-IR) method was used for IR level determination. The expression of oestrogen receptor α (ERα) and glucose transporter 4 (GLUT4) genes in the uterus was examined by real-time polymerase chain reaction. Liver hexokinase (HK) and glucokinase (GK) activity was determined using spectrophotometry. Quercetin significantly improved the IR state in PCOS rats. PCOS resulted in a decrease in liver GK and an increase in liver HK specific activity, whereas quercetin increased both liver HK and GK activity. Our data also showed a significant reduction in uterine ERα and GLUT4 expression in the PCOS group, which was increased by quercetin. A remarkable effect of quercetin was the intensive reduction of PCOS-IR and significant induction of uterine GLUT4 and ERα gene expression; it could thus be a possible effective treatment for PCOS and its complications, IR and infertility. Insulin resistance (IR) and infertility are two major complications of polycystic ovary syndrome (PCOS). We found that quercetin as a natural flavonoid improved the IR state and increased expression of two important fertility related genes in the uterus of PCOS rats; it could thus be a possible treatment for PCOS and infertility. [ABSTRACT FROM AUTHOR]

Background: Bioactivation of nitroglycerin (NTG) leads to the production of reactive oxygen species and reactive nitrogen species. The aim of this study was to investigate the effects of NTG treatment on the redox homeostasis in rat uterus around the time of implantation and the number of pups. Materials and Methods: The rats in long-term test groups were treated subcutaneously with NTG (15mg/kg BW) and normal saline (1ml/kg B) in control groups for 4 weeks. Afterwards, they were mated and divided into four groups. Two groups were treated until 5 days after mating. Thereafter, they were sacrificed and the activities of glutathione peroxidase (GPx), catalase (CAT), and glutathione reductase as well as the levels of reduced glutathione (GSH) and malondialdehyde (MDA) in the uterus homogenates were measured. In other two groups, treatments were continued until their pups were counted. In the short-term groups, treatments were started after mating, and all above parameters were measured as similar as long-term groups. Results: Long-term NTG treatment significantly increased MDA level and decreased the GPx activity and the pups number compared to the controls (p<0.05), whereas no marked alteration in the activities of GR and CAT and the levels GSH were observed. However, short-term NTG treated groups showed no significant changes in all the parameters mentioned above as compared with the controls. Conclusion: Long-term NTG treatment, unlike short-term treatment, may cause impaired implantation and infertility, but there is also room for further improvement. [ABSTRACT FROM AUTHOR]

The goal of this study was to evaluate the protective and mitigative effect of vitamin C on oxidative stress in differentiated thyroid cancer (DTC) patients ablated with radioiodine. 58 DTC patients selected for radioactive iodine therapy (RAIT) with 5550 MBq 131Iodine were divided into four groups. Group 1 (control group) consisted of patients who underwent RAIT routinely. Other patients received 1500 mg vitamin C daily 2 days after (group 2), 2 days before to 2 days after (group 3) and 2 days before RAIT (group 4). Serum oxidative stress markers including malondialdehyde (MDA), glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) were measured immediately before and 2 days after RAIT. A significant increase in MDA after RAIT was observed in all groups (p < 0.05). The concentrations of MDA were significantly higher in the control group compared to the intervention groups (p < 0.05). A significant decrease in the control group (p < 0.05) and increase in group 4 (p < 0.05) were observed in GSH level after RAIT (p < 0.05). Mean variation of GSH was significant between control group with groups 3 (p < 0.01) and 4 (p < 0.01). The results indicate that activity of SOD remained unchanged in all groups (p > 0.05). A significant increase was observed in CAT activity after RAIT in all groups (p < 0.05), which was higher in control group than intervention groups. In groups 3 (p < 0.05) and 4 (p < 0.05), this increase in CAT activity was significantly lower than the control group. RAIT causes serum oxidative stress, which can be ameliorated using vitamin C as an antioxidant. These results indicate that radioprotective effect of vitamin C is preferable to its mitigative effect. [ABSTRACT FROM AUTHOR]

Some types of cancers show a strong relationship with diabetes and play a central role in mortality in the patient population suffering from diabetes mellitus. In this study, HepG2 cells have been used to investigate the toxic effects of hyperglycemia and/or quercetin (Q) on mammalian target of rapamycin (m-TOR) and nuclear factor erythroid 2-related factor 2 (Nrf-2) expression as central molecules involved in cancer. HepG2 cells were cultured with different concentrations of glucose (5.5, 30, and 50 mM) and/or Q (25 µM) for 48 and 72 h. Effects of glucose and/or Q on m-TOR and Nrf-2 expression were assayed by quantitative real-time PCR (qRT-PCR). qRT-PCR results revealed that 30 and 50 mM of glucose increased m-TOR expression at 48 h, although after 72 h, only 30 mM had an increasing effect. At 50 mM, glucose-induced Nrf-2 gene expression after both 48 and 72 h. The results also showed that 25 µM of Q reduced m-TOR and Nrf-2 expression at both 30 and 50 mM after 48 and 72 h incubation. Q has potential effects on reducing oxidative stress caused by hyperglycemia and during diabetes may be able to modulate some carcinogenic signaling pathways. [ABSTRACT FROM AUTHOR]

Nicotine is a natural component of tobacco plants and is responsible for the addictive properties of tobacco. Nicotine has been recognized to result in oxidative stress by inducing the generation of reactive oxygen species (ROS). The purpose of this work was to estimate the hepatotoxicity effect of nicotine on viability and on antioxidant defense system in cultures of HepG2 cell line and the other hand, ameliorative effect of quercetin (Q) as an antioxidant was analyzed. Nicotine induced concentration dependent loss in HepG2 cell line viability. The results indicated that nicotine decreased activity of superoxide dismutase (SOD) and glutathione reductase (GR) and increased activities of catalase (CAT) and glutathione peroxidase (GPx) and glutathione (GSH) content in the HepG2 cells. Q significantly increased activity of SOD, GR and GSH content and decreased activity of GPX in nicotine + Q groups. Our data demonstrate that Q plays a protective role against the imbalance elicited by nicotine between the production of free radicals and antioxidant defense systems, and suggest that administration of this antioxidant may find clinical application where cellular damage is a consequence of ROS. [ABSTRACT FROM AUTHOR]

Background: This study aimed to assess several biochemical and oxidative stress parameters before and after radioiodine therapy in patients with well-differentiated thyroid cancer who consumed a low iodine diet and withdrawal of levothyroxine after total thyroidectomy. Methods: We enrolled 40 candidates for radioiodine therapy. Blood sampling was performed prior to as well as 72 h after consumption of 125-200 mCi of 1311. Total protein, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and creatinine were measured. Oxidative stress parameters that included malondialde-hyde and protein carbonyl levels were also assessed. Results: There were significantly decreased total protein, creatinine, aspartate aminotransferase, and alanine aminotransferase levels (P<0.00\) after treatment. However, malondialdehyde levels increased significantly (P<0.05) over the studied time. Conclusion: We found that radioactive iodine absorption in peripheral tissues due to a low-iodine diet and levothyroxine withdrawal could relieve iodine deficiency in the liver and kidneys which resulted in reduced total protein, aspartate aminotransferase, alanine aminotransferase, and creatinine levels. However, it induced oxidative stress by increasing malondialdehyde levels in the blood. [ABSTRACT FROM AUTHOR]

Cigarette smoke is a complex mixture of toxic chemicals, including nicotine, carbon monoxide, and several recognized carcinogens and mutagens. Nicotine has a direct disturbing influence on steroid hormones (estrogen and progesterone), which are essential components of the female reproductive system, but the effect of nicotine on the hormone receptors is not yet clear. The aim of this study was to elucidate the effect of nicotine on the expression of estrogen receptor (ER), progesterone receptor (PR), and vascular endothelial growth factor (VEGF) in endometrial stromal cells. Expression levels of PR, ER, and VEGF in human endometrial stromal primary cells treated with nicotine (0, 10−11, 10−8, and 10−6 μM) for 24 h were measured by quantitative real-time PCR. MTT assay demonstrated that nicotine decreased cell viability in a dose-dependent manner. Real-time PCR data showed that despite decrease in ER expression in the nicotine-treated groups compared with the control, nicotine exerted an increased inhibitory effect on PR expression compared to that on ER expression. VEGF mRNA expression in nicotine-treated endometrial stromal cells was increased. The results from this study provide novel evidence for inhibitory effects of nicotine on steroid hormones receptor expression in human primary endometrial cells. Also, our data suggest that nicotine might have angiogenesis effects on these cells. [ABSTRACT FROM PUBLISHER]

Background and objective: Cyclosporine A (CsA) is an immunosuppressive agent administered to transplant patients. A well-known reported oral side effect of CsA consumption is gingival overgrowth (GO). Changes in the expression of integrins occurring in the gingiva following CsA treatment have been reported but these reports are mainly concerned with the connective tissue of the gingiva. In this study we targeted the alterations in the oral epithelium using KB cells, an oral epithelial cell line. Methods: Cultured oral epithelial cells were treated with increasing concentrations of CsA (0.1, 1 and 10 µg/mL) and the molecular changes involving antioxidant enzymes [glutathione peroxidase (GPx) and glutathione reductase (GR)] and the level of reactive oxygen species (ROS) were measured. Quantitative real-time PCR was used to assess the expression of selected integrins (α2, α5 and β1). Results: At CsA concentration above 0.1 µg/mL GPx demonstrated an increase in activity while GR activity and the level of reduced glutathione were diminished ( p < 0.05). α5 and β1 integrin were downregulated at all treatment concentrations of CsA while α2 integrin presented this effect at concentrations above 1 µg/mL ( p < 0.05). Conclusion: The results suggest a possible role for oxidative stress and the altered expression of integrins in the pathology of CsA-induced gingival overgrowth. [ABSTRACT FROM AUTHOR]

Objectives: Propranolol, a beta-adrenergic blocker, is used in the treatment of a large number of cardiovascular diseases such as hypertension and arrhythmias. Propranolol, in combination with furosemide, is used to treat hypertensive disorders although their side effect profile is not very obvious. In present study, the effects of the drugs furosemide and propranolol were in corporately investigated both on glutathione homeostasis and their antioxidant effect on ACHN cells. Methods: The cytoxicities and antioxidant effects of these two clinically important drugs on human kidney cell lines were evaluated using MTT following by the determination of glutathione reductase (GR) and glutathione peroxidase (GPx) activities and measuring the level of reduced glutathione (GSH). Results: Propranolol induced a significant cytotoxic effect at 100 µM, while furosemide was cytotoxic at doses of 250 and 1000 µg/ml. A slight increase in GPx and GR activities and GSH level was observed with propranolol and furosemide treatment alone, while the two drugs together caused a significant increase in GPx and GR activities (35% and 42%, respectively) and GSH content (35%) in ACHN cell lysates ( p < 0.05). Conclusions: Our results demonstrate that although high doses of furosemide and propranolol are cytotoxic, co-administration of low doses may improve the antioxidant defense in patients undergoing treatment with these two important drugs. [ABSTRACT FROM AUTHOR]

Purpose: Oxidative stress and renin- angiotensin system are both involved in the pathophysiology of most of the systemic and central disorders as well as in aging. Angiotensin converting enzyme (ACE) inhibitors, well known for their cardiovascular beneficial effects, have also shown antioxidant properties in pathologic conditions. This study aimed to evaluate the central effect of ACE inhibitors on oxidative status under no pathologic condition. Methods: Adult male rats were divided into four groups of 9 rats each. Groups were treated orally by perindopril at the doses of 1, 2, 4 mg/kg/day or normal saline as the control for four consecutive weeks. At the end of the treatment period the reduced and oxidized glutathione (GSH and GSSG respectively) and malondialdehyde (MDA), the product of lipid peroxidation, were measured in the rats' hippocampus. Results: The GSH increased dose dependently and was significantly higher in the 2 mg/kg perindopril treated group than the control group (p<0.05) while the GSSG level remained unchanged. As a consequent, the ratio of GSH to GSSG increased significantly in a dose dependent manner. There was not any significant change in MDA. Conclusion: This study demonstrated that ACE inhibition may cause an increase in GSH as an anti- oxidant defense in the hippocampus. [ABSTRACT FROM AUTHOR]

Objective: Combined oral contraceptives (COCs) have some adverse effects on the serum lipid profile. Because hyperlipidemia is one of the risk factors in cardiovascular diseases, lipid abnormalities should be evaluated in women consuming COCs. Vitamins E and C are known to have beneficial effects on serum lipid profiles. Therefore, in this study, we evaluated the effects of vitamins E and C on serum lipids in women using COCs. Methods: The study compared changes in lipid parameters with and without vitamin therapy in women consuming COCs compared to those of a control group (40 non-contraceptive users or NCU) for 4 weeks. Total cholesterol and triglyceride, low-density lipoprotein (LDL), and highdensity lipoprotein (HDL) levels along with HDL/LDL ratios were measured for all participants. Results: COC users experienced significantly higher increases in the levels of triglycerides and LDL than non-users (p<0.05). However, no significant differences were noted in the total cholesterol and HDL levels. In the treated COC group receiving vitamins E and C, the HDL level and the HDL/LDL ratio increased and the LDL and triglycerides levels decreased significantly compared with those of the other groups. Conclusion: The results of our study indicate that supplementation with antioxidant vitamins E and C restores a normal lipid profile in COC users. [ABSTRACT FROM AUTHOR]

Airway wall remodeling comprises a broad range of structural changes including increases in the volume of airway smooth muscle (ASM) and fibrillar collagen. The impact of fibrillar collagen remodeling on ASM proliferation was investigated. Human ASM cultured on type I fibrillar collagen remodeled the collagen substrate by both degradation (collagenolysis) and fonnation of networks comprised of thicker reticular collagen fibrils (fibrillogenesis). In cultures maintained on fibrillar collagen, the levels of matrix metalloproteases (MMPs) -1 and -14 mRNA and active MMP-2 were higher than in cultures maintained on non-fibrillar type I collagen (gelatin) or plastic. Although there was no apparent increase in cytotoxicity or apoptosis, the number of ASM was lower on fibrillar collagen than on gelatin or plastic for control conditions. Furthermore, maintenance on fibrillar collagen attenuated basic fibroblast growth factor-stimulated increases in cell number and the percentage of cells entering S-phase. In cultures maintained on fibrillar collagen, the MMP inhibitor ilomastat (2.5 μM) I) attenuated collagenolysis, 2) enhanced fibrillogenesis, and 3) inhibited proliferation. In contrast, knockdown of the β1-integrin gene in ASM maintained on fibrillar collagen led to an increase in proliferation and reduced MMP- 1 and -14 expression. Thus, ASM remodel the pencellular environment by degrading collagen fibrils and spinning them into larger collagen assemblies. Moreover, the collagen fibrils limit proliferation and activate autocrine MMPs in a β-integrin-dependent manner, suggesting a potential negative feedback on modeling executed through fibrillar collagen activation of 31-integrins. [ABSTRACT FROM AUTHOR]

Aim: Cyclosporine A (CsA) is the most widely used immunosuppressive drug in transplant surgery. It is able to generate reactive oxygen species (ROS) and cause lipid peroxidation (thiobarbituric acid-reacting substances [TBARS]), which will directly result in CsA hepatotoxicity. Methods: In this study, the potential of quercetin (Q) and vitamin E (E), in attenuating CsA-induced liver dysfunction in rats was investigated. Male Sprague–Dawley rats were divided into six groups and treated with either olive oil, ethanol + olive oil, CsA, CsA + E, CsA + Q, or CsA + E + Q for both 4 and 8 weeks. Hepatotoxicity was assessed by morphological alterations in tissue architecture and by reduced serum total protein and increased serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. Results: The results indicated that CsA treatment increases TBARS and decreases activities of catalase (CAT) and glutathione peroxidase (GPx) in the rat liver. The co-administration of E and Q with CsA treatment improved both liver morphology changes and function. A combination of these antioxidants significantly reduced TBARS and increased CAT and GPx activities in the hepatic tissue. Conclusion: Our data demonstrates that E + Q plays a protective role against the imbalance elicited by CsA between the production of free radicals and antioxidant defence systems, and suggests that a combination of these two antioxidants may find clinical application where cellular damage is a consequence of ROS. [ABSTRACT FROM AUTHOR]

1. The aim of the present study was to investigate the effects of vitamin E and/or quercetin (Q) on renal function, oxygen radical concentrations in the kidney and some anti-oxidant enzyme activities in rats treated with cyclosporine A (CsA). 2. Groups of rats (270 ± 15 g), on standard rat chow and water, received all their treatments by gavage for either 4 or 8 weeks. Control groups received either olive oil (0.5 mL) or 25% ethanol (0.5 mL) + olive oil (0.5 mL) per day as vehicle. All experimental groups received 25 mg CsA/kg per day in 0.5 mL olive oil. The vitamin E group received 100 mg vitamin E/kg per day in olive oil in addition to CsA treatment. The quercetin group received 15 mg of Q/kg per day in 0.5 mL of 25% ethanol in addition to CsA treatment. The vitamin E + quercetin group received the two anti-oxidants at the concentrations given in addition to CsA treatment. 3. Quercetin, at a concentration less than one-quarter of vitamin E, was more efficient in lowering blood urea nitrogen, serum creatinine and kidney malondialdehyde in CsA-treated rats. However, neither of the two anti-oxidants was able to normalize these analytes to control values after either 4 or 8 weeks treatment. 4. Quercetin (50 µmol/kg per day) elevated all renal anti-oxidant enzyme activities to values observed in the negative controls. However, vitamin E (232 µmol/kg per day) only normalized glutathione peroxidase activity at the end of either 4 or 8 weeks treatment. Combination treatment with the two anti-oxidants abolished all the ill-effects of CsA. 5. Combination treatment with the two anti-oxidants of renal transplant patients receiving CsA may be beneficial in ameliorating the chronic nephrotoxic effects of the important immunosuppressive drug CsA. [ABSTRACT FROM AUTHOR]