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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.

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]

Objective: To examine the effect of quercetin on stereological parameters and autophagy-related genes in ovaries of polycystic ovary syndrome (PCOS) rats. Methods: Fifty female Sprague-Dawley rats were randomly divided into five groups: the control group, the ethanol group, the quercetin group (15 mg/kg/day), the PCOS group, as well as the PCOS + quercetin group. After the induction of PCOS, quercetin was administered orally for 30 days. Histological, stereological and real-time PCR analyses were carried out to evaluate the effect of quercetin on PCOS rats. Results: Stereological analysis revealed that quercetin significantly increased the number of ovarian follicles and the volume of corpus luteum and induced a significant decrease in atretic follicles in comparison to the PCOS group. In addition, quercetin markedly increased mTOR gene expression while decreasing Beclin-1 and LC3 gene expression. Conclusions: Quercetin strongly modulates the expression of ovarian autophagy-related genes and stereological parameters in PCOS rats. Therefore, it can be considered as an ameliorative component for ovarian follicular impairments. [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]

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 formation 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 nonfibrillar 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 [micro]M) 1) attenuated collagenolysis, 2) enhanced fibrillogenesis, and 3) inhibited proliferation. In contrast, knockdown of the [beta]1-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 pericellular environment by degrading collagen fibrils and spinning them into larger collagen assemblies. Moreover, the collagen fibrils limit proliferation and activate autocrine MMPs in a [beta]-integrin-dependent manner, suggesting a potential negative feedback on modeling executed through fibrillar collagen activation of [beta]-integrins. asthma; extracellular matrix; integrin; matrix metalloprotease; proliferation doi:10.1152/ajplung.00312.2009

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]

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]

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]

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]

A high risk of reproductive disorders can be seen in diabetic pregnancy. Reproductive disorders associated with diabetes may result from alterations in the function of the ovary. In this study, we investigated the ameliorative effects of quercetin as a phytoestrogen and antidiabetic agent on the folliculogenesis in diabetic mice. Streptozotocin-induced diabetic mice were treated with 30 mg/kg/day quercetin for four weeks. The volume of ovary, follicles, and corpus luteum were significantly decreased in the diabetic mice. The number of growing follicles (secondary, antral, and Graafian follicles) and corpus luteum was significantly decreased in the diabetic mice. Also, the volume of oocytes was significantly decreased in antral and Graafian follicles. Our results indicated that the administration of quercetin in diabetic mice increased the volume of the ovary and growing follicles, the number of growing follicles and corpus luteum. It also significantly decreased the number of atretic follicles. As a result, it may be concluded that the impaired follicular growth and development caused by hyperglycemia in diabetic mice can be alleviated by quercetin treatment. [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]

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]