Association of endometriosis and breast cancer: mini review of the literature

Background: Endometriosis is a common, estrogen-dependent, gynecological disease, which is defined as the presence of endometrial tissue outside the uterine cavity. Current data have associated endometriosis with specific malignancies, including ovarian and breast cancer. Purpose: The purpose of our study is to summarize and present published literature providing evidence regarding the possible relationship between endometriosis and breast cancer. Methods: Pubmed and Scopus databases were searched systematically for studies that sought to identify a potential association of endometriosis and breast cancer. 15 relevant articles were retrieved and included in the present review. Results: A small number of observational studies have shown a correlation of endometriosis and breast cancer. Other studies found that the risk of breast cancer increases with age. The scenario of an early interruption of the inflammatory process, derived from endometriosis, by oophorectomy and a possible consequent decrease in the risk of breast cancer has also been proposed. The hypothesis that both conditions could be related through common mutations on BRAC1 and BRAC2 genes has also been investigated. Conclusion: The available published evidence is inconclusive. Further studies are needed to evaluate the association of endometriosis and breast cancer and the possible pathogenetic pathways that relate the two disorders. © 2015, Springer-Verlag Berlin Heidelberg

Effects of adult-onset streptozotocin-induced diabetes on the rat brain antioxidant status and the activities of acetylcholinesterase, (Na +,K+)- and Mg2+-ATPase: Modulation by L-cysteine

Uncontrolled diabetes is known to affect the nervous system. The aim of this study was to investigate the effect of the antioxidant L-cysteine (Cys) on the changes caused by adult-onset streptozotocin (STZ)-induced diabetes on the rat brain total antioxidant status (TAS) and the activities of acetylcholinesterase (AChE), (Na+,K+)-ATPase and Mg 2+-ATPase. Thirty-eight male Wistar rats were divided into six groups: CA (8-week-control), CB (8-week-control + 1-week-saline-treated), C + Cys (8-week-control + 1-week-Cys-treated), D A (8-week-diabetic), DB (8-week-diabetic + 1-week-saline-treated) and D + Cys (8-week-diabetic + 1-week-Cys-treated). All diabetic rats were once treated with an intraperitoneal (i.p.) STZ injection (50 mg/kg body weight) at the beginning of the experiment, while all Cys-treated groups received i.p. injections of Cys 7 mg/kg body weight (daily, for 1-week, during the 9th-week). Whole rat brain parameters were measured spectrophotometrically. In vitro incubation with 0.83 mM of Cys or 10 mM of STZ for 3 h was performed on brain homogenate samples from groups CB and DB, in order to study the enzymes' activities. Diabetic rats exhibited a statistically significant reduction in brain TAS (-28%, D A vs CA;-30%, DB vs CB) that was reversed after 1-week-Cys-administration into basal levels. Diabetes caused a significant increase in AChE activity (+27%, DA vs CA; +15%, DB vs CB), that was further enhanced by Cys-administration (+57%, D + Cys vs CB). The C + Cys group exhibited no significant difference compared to the CB group in TAS (+2%), but showed a significantly increased AChE activity (+66%, C + Cys vs C B). Diabetic rats exhibited a significant reduction in the activity of Na+,K+-ATPase (-36%, DA vs C A;-48%, DB vs CB) that was not reversed after 1-week Cys administration. However, in vitro incubation with Cys partially reversed the diabetes-induced Na+,K+-ATPase inhibition. Mg2+-ATPase activity was not affected by STZ-induced diabetes, while Cys caused a significant inhibition of the enzyme, both in vivo (-14%, C + Cys vs CB;-17%, D + Cys vs CB) and in vitro (-16%, D B + in vitro Cys vs CB). In vitro incubation with STZ had no effect on the studied enzymes. The present data revealed a protective role for Cys towards the oxidative effect of diabetes on the adult rat brain. Moreover, an increase in whole brain AChE activity due to diabetes was recorded (not repeatedly established in the literature, since contradictory findings exist), that was further increased by Cys. The inhibition of Na +,K+-ATPase reflects a possible mechanism through which untreated diabetes could affect neuronal excitability, metabolic energy production and certain systems of neurotransmission. As concerns the use of Cys as a neuroprotective agent against diabetes, our in vitro findings could be indicative of a possible protective role of Cys under different in vivo experimental conditions. © 2009 Springer Science+Business Media, LLC

The neuroprotective role of l-cysteine towards the effects of short-term exposure to lanthanum on the adult rat brain antioxidant status and the activities of acetylcholinesterase, (Na+,K+)- and Mg 2+-ATPase

Lanthanum (La) is a rare earth element that is widely used for industrial, medical and agricultural purposes. Its neurotoxic effects are linked to its physical and chemical properties and its interaction with certain trace elements and membrane-bound enzymes. The aim of this study was to investigate the effects of short-term La-administration (as LaCl3, 53 mg/kg) on the adult rat whole brain total antioxidant status (TAS) and the activities of acetylcholinesterase (AChE), Na+,K+-ATPase and Mg 2+-ATPase, as well as the potential effect of the co-administration of the antioxidant l-cysteine (Cys, 7 mg/kg) on the above parameters. Twenty-eight male Wistar rats were divided into four groups: A (saline-treated control), B (La), C (Cys),and D (La and Cys). All rats were treated once daily with intraperitoneal injections of the tested compounds, for 1-week. Rats were sacrificed by decapitation and the above mentioned parameters were measured spectrophotometrically. Rats treated with La exhibited a significant reduction in brain TAS (-36%, P < 0.001, BvsA), that was partially limited by the co-administration of Cys (-13%, P < 0.01, DvsA), while Cys (group C) had no effect on TAS. The rat brain AChE activity was found significantly increased by both La (+23%, P < 0.001, BvsA) and Cys (+59%, P < 0.001, CvsA), while it was adjusted to control levels by the co-administration of La and Cys. The activity of rat brain Na+,K+-ATPase was significantly decreased by La-administration (-28%, P < 0.001, BvsA), while Cys supplementation could not reverse this decrease. The activity of Mg 2+-ATPase exhibited a slight but statistically significant reduction due to La (-8%, P < 0.01, BvsA), that was further reduced by Cys co-administration (-25%, P < 0.001, DvsA). The above findings suggest that La short-term in vivo administration causes a statistically significant decrease in the rat brain TAS and an increase in AChE activity. Both effects can be, partially or totally, reversed into control levels by Cys co-administration, which could thus be considered for future applications as a neuroprotective agent against chronic exposure to La. The activities of Na+,K +- and Mg2+-ATPase that were inhibited by La, could not be reversed by Cys co-administration. A role for the already reported concentration-dependent interaction of La with Ca-binding sites (such as Ca 2+-ATPase) might be considered for certain of the above phenomena. © 2008 Springer Science+Business Media, LLC

Effects of adult-onset choline deprivation on the activities of acetylcholinesterase, (Na+,K+)- and Mg2+-ATPase in crucial rat brain regions

Choline (Ch) plays an important role in brain neurotransmission, while Ch-deprivation (CD) has been linked to various pathophysiological states. Prolonged ingestion of Ch-deficient diet (CDD) is known to produce CD causing a reduction of rat brain acetylcholine (ACh) levels, as well as memory and growth disorders. The aim of this study was to investigate the effect of a 2-month adult-onset CD on the activities of acetylcholinesterase (AChE), (Na+,K+)- and Mg2+-ATPase in crucial brain regions of male rats. Adult rats were divided into two groups (control and CD). The CD group was fed with CDD for 2-months. At the end of the second month, rats were sacrificed by decapitation and the brain regions were rapidly removed. Enzyme activities were measured spectrophotometrically in the homogenated frontal cortex, hippocampus, hypothalamus, cerebellum, and pons. In CD rats, AChE activity was found statistically significantly increased in the hippocampus and the cerebellum (+28%, P < 0.001 and +46%, P < 0.001, respectively, as compared to control), while it was found unaltered in the other three regions (frontal cortex, hypothalamus and pons). (Na+,K+)-ATPase activity was found increased by CD in the frontal cortex (+30%, P < 0.001), decreased in both hippocampus and hypothalamus (-68%, P < 0.001 and -51%, P < 0.001, respectively), and unaltered in both cerebellum and pons. No statistically significant changes were observed in the activities of Mg2+-ATPase in the frontal cortex and the hypothalamus, while statistically significant increases were recorded in the hippocampus (+21%, P < 0.01), the cerebellum (+85%, P < 0.001) and the pons (+19%, P < 0.05), as compared to control levels. Our data suggest that adult-onset CD can have significant effects on the examined brain parameters in the examined crucial brain regions, as well as that CD is a metabolic disorder towards which different and brain region specific neurophysiological responses seem to occur. Following a 2-month adult-onset CD, the activity of AChE was found to be increased in the hippocampus and the cerebellum and unaltered in the other three regions (frontal cortex, hypothalamus and pons), while Na+,K+-ATPase activity was found to be increased in the frontal cortex, decreased in both hippocampus and hypothalamus, and unaltered in both cerebellum and pons. Moreover, Mg2+-ATPase activity was found to be unaltered in the frontal cortex and the hypothalamus, and increased in the hippocampus, the cerebellum and the pons. The observed differentially affected activities of AChE, (Na+,K+)-ATPase and Mg2+-ATPase (induced by CD) could result in modulations of cholinergic neurotransmission, neural excitability, metabolic energy production, Mg2+ homeostasis and protein synthesis (that might have a variety of neurophysiological consequences depending on the brain region in which they seem to occur). © 2008 Elsevier Ltd. All rights reserved

Effects of short-term exposure to manganese on the adult rat brain antioxidant status and the activities of acetylcholinesterase, (Na +,K+)-ATPase and Mg2+-ATPase: Modulation by L-cysteine

Manganese (Mn) is an essential metalloenzyme component that in high doses can exert serious oxidative and neurotoxic effects. The aim of this study was to investigate the potential effect of the antioxidant l-cysteine (Cys, 7 mg/kg) on the adult rat brain total antioxidant status (TAS) and the activities of acetylcholinesterase (AChE), Na+,K+-ATPase and Mg 2+-ATPase induced by short-term Mn administration (as Mn chloride, 50 mg/kg). Twenty-eight male Wistar rats were divided into four groups: A (saline-treated control), B (Mn), C (Cys) and D (Mn and Cys). All rats were treated once daily, for 1 week with intraperitoneal injections of the tested compounds. Rats were killed by decapitation and mentioned parameters were measured spectrophotometrically. Rats treated with Mn exhibited a significant reduction in brain TAS (-39%, P < 0.001, B versus A) that was partially reversed by Cys co-administration (-13%, P < 0.01, D versus A), while Cys (group C) had no effect on TAS. The rat brain AChE activity was found significantly increased by both Mn (+21%, P < 0.001, B versus A) and Cys (+61%, P < 0.001, C versus A), while it was adjusted into the control levels by the co-administration of Mn and Cys. The activity of rat brain Na +,K+-ATPase was not affected by Mn administration, while Mg2+-ATPase exhibited a slight but statistically significant reduction in its activity (-9%, P < 0.01, B versus A) due to Mn, which was further reduced by Cys co-administration. The above findings suggest that short-term Mn in vivo administration causes a statistically significant decrease in the rat brain TAS and an increase in AChE activity. Both effects can be, partially or totally, reversed into the control levels by Cys co-administration (which could thus be considered for future applications as a neuroprotective agent against chronic exposure to Mn and the treatment of manganism). The activity of Na+,K+-ATPase is not affected by Mn, while Mg2+-ATPase activity is slightly (but significantly) inhibited by Mn, possibly due to Mg replacement. © 2008 The Authors