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The aim of the present study was to investigate the effects of cadmium (Cd) (5 and 50 mg Cd/l in drinking water) and ethyl alcohol (ethanol, EtOH) (5 g EtOH/kg b.wt., intragastrically), administered alone or simultaneously, on the concentrations of pro-inflammatory (interleukin-1, IL-1α; interleukin-6, IL-6; tumor necrosis factor-α, TNFα and interferon γ, INFγ) and anti-inflammatory (interleukin-4, IL-4) cytokines in the serum of rats. In order to estimate the involvement of Cd- or/and EtOH-induced oxidative stress in damage to cytokines, the concentration of protein carbonyl groups (PC), as a marker of oxidative protein damage, was also determined. Exposure to 5 and 50 mg Cd/l, alone or in combination with EtOH, led to an increase in the serum concentrations of IL-1α, TNFα and INFγ with a simultaneous decrease in IL-4 concentration, compared to the control. The concentration of IL-6 was elevated only after administration of 50 mg Cd/l, both alone and in combination with EtOH. The exposure to EtOH alone resulted in increased concentrations of TNFα and INFγ, as well as in decreased concentrations of IL-4. In rats co-exposed to Cd and EtOH, the changes observed in the concentrations of the cytokines, except in IL-6, were more advanced, compared to the animals treated with these xenobiotics alone. Exposure to Cd and EtOH, both alone and in combination, caused an increase in the serum PC concentration. The concentration of PC positively correlated with the concentrations of IL-1α, IL- 6, TNFα and INFγ and negatively with IL-4 concentration. The results suggest that changes in the cytokines examined are more enhanced after combined exposure to Cd and EtOH, especially at higher Cd dosage. Moreover, it can be hypothesized that oxidative stress may be involved in the mechanism leading to changes in the concentration of cytokines after exposure to Cd and EtOH alone and in combination. [ABSTRACT FROM AUTHOR]

The activity of glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) was investigated in liver and kidney of rats exposed to cadmium (Cd) and ethanol (EtOH) alone and in combination. Rats were treated with 50 mg Cd/dm³ in drinking water and/or 5 g of EtOH/kg body wt/24 h intragastrically, for 12 weeks. Exposure to Cd led to an increase in GPx and GST activity with a simultaneous decrease in GR activity in the liver. In the kidney of rats treated with Cd, an increase in the activity of GPx and GR was noted. In the EtOH-exposed rats, GPx activity decreased in the liver, but increased in the kidney. Exposure to EtOH caused a reduction in GR activity only in the liver. The co-exposure to Cd and EtOH led to an increase in the liver and kidney GPx activity compared to control. In the rats simultaneously exposed to Cd and EtOH liver activity of GR decreased compared to control, whereas the kidney GR activity increased compared to control as well as to the groups treated with Cd and EtOH seperately. The co-exposure to Cd and EtOH led to an increase in the liver activity of GST compared to the control and EtOH groups. Analysis of variance (ANOVA/MANOVA) revealed that the changes noted in the activity of investigated enzymes in the Cd + EtOH group resulted from the independent action of both Cd or EtOH as well as from their interactive action. Numerous correlations (negative or positive) were noted between the activity of GPx, GR and GST, and the concentration of GSH, Cd and MDA in the liver and kidney. On the basis of our results it can be concluded that changes in the activity of GPx, GR and GST in the liver and kidney may be involved in the mechanism leading to a decrease in GSH concentration in these organs due to exposure to Cd and EtOH alone and in conjunction with each other. [ABSTRACT FROM AUTHOR]

The aim of our study was to evaluate oxidative stress in hepatic mitochondria of rats exposed for 12 weeks alone and in conjunction to cadmium (Cd) (50 mg Cd/dm³, in drinking water) and ethanol (EtOH) (5g of EtOH/kg body wt, intragastrically). In hepatic mitochondria the concentrations of malondialdehyde (MDA), hydrogen peroxide (H2O2), reduced glutathione (GSH) and the activities of manganese superoxide dismutase (MnSOD), glutathione peroxidase (GPx) and glutathione reductase (GR) were measured. After exposure to Cd, an increase in MDA and H2O2 concentrations with a simultaneous decrease in GSH concentration and the activities of MnSOD, GPx and GR were noted. Exposure to EtOH caused an increase in MDA and H2O2 concentration, as well as MnSOD and GPx activities and a decrease in GSH concentration and GR activity. Co-exposure to Cd and EtOH caused an increase in MDA and H2O2 concentration as well as in MnSOD activity and resulted in a decrease in GSH concentration as well as GPx and GR activities in comparison to the control group. The increase in H2O2 concentration and MnSOD activity as well as the decrease in GSH concentration were significant compared to the animals exposed to Cd alone. The changes noted in the investigated parameters in hepatic mitochondria of the rats co-exposed to Cd and EtOH resulted from an independent action of Cd (H2O2, GSH and GPx) or EtOH (H2O2, GSH and MnSOD) as well as from their mutual interaction (GSH, MnSOD and GPx). Based on all results, it can be concluded that exposure to Cd and EtOH, both alone and in conjunction, leads mainly to changes in the concentration of H2O2 and GSH and MnSOD activity in the liver mitochondria. [ABSTRACT FROM AUTHOR]

In the present study, the effect of co-exposure to cadmium (Cd) and ethanol (EtOH) on concentrations of vitamins E and C were evaluated in the liver and kidney homogenates of rats which were administered, singly or in combination, Cd (50 mg Cd/dm³ in drinking water) and EtOH (5 g EtOH/kg b. wt./24 h, intragastrically) for 12 weeks. The exposure to Cd caused a decrease in the concentration of vitamins E and C in the liver, whereas the concentration of vitamin E increased in the kidney, compared to control group. EtOH administration led to a decrease in vitamins E and C concentrations in the liver. Exposure to Cd alone enhanced the concentration of vitamin C in the kidney. In the co-exposed group, the concentration of vitamin E decreased in the liver as compared to control and Cd group but increased in comparison to EtOH group. The concentration of vitamin C in this organ decreased compared to control and Cd- or EtOH-exposed groups. The co-exposure to both substances caused a rise in vitamin E concentration in the kidney compared to control and EtOH groups, whereas the concentration of vitamin C increased compared to control and Cd group. In the liver positive correlation was noted between vitamin E or C concentrations and glutathione (GSH) concentration. In the kidney, negative correlation was found between the concentration of vitamin E and GSH. No correlation was observed between the concentration of vitamin C and GSH in this organ. The results obtained suggest that the change in vitamin E concentration in the liver of rats co-exposed to Cd and EtOH resulted from an independent action of EtOH and its interaction with Cd, whereas in the kidney it was due to an independent Cd effect. In the animals co-exposed to Cd and EtOH, the change in vitamin C detected in the liver was the result of an independent action of either Cd or EtOH. In the kidney, the concentration of vitamin C was only EtOH-dependent. The results of this study together with our previous finding in the model used suggest the involvement of vitamins E and C in the development of Cd- and/or EtOH-induced oxidative stress. [ABSTRACT FROM AUTHOR]

The involvement of some low-molecular thiol compounds in the mechanisms of peroxidative action of cadmium (Cd) and ethanol (EtOH) was studied. Concentrations of reduced glutathione (GSH), metallothionein (Mt) and thiol (-SH) groups in protein and non-protein fractions were assessed in the homogenates of the liver and kidney of rats exposed to Cd (50 Cd/dm³ of drinking water) and EtOH (5 g EtOH/kg body weight/24 h, intragastrically), singly or in combination, for 12 weeks. Exposure to Cd caused a reduction in the concentration of GSH and non-protein SH groups in the liver and kidneys with a simultaneous increase in Mt level in these organs. The concentration of total SH groups increased only in kidneys. Administration of EtOH had no effect on Mt concentration in both organs, but caused a reduction in the concentration of GSH and non-protein SH groups. A reduction in the level of total SH groups following exposure to EtOH was also noted in the liver. In the group of rats with a simultaneous exposure to Cd and EtOH, GSH concentration was decreased in the liver compared to the control and Cd-exposed animals, and in the kidney in comparison to the control and EtOH-receiving rats. Following the combined exposure to Cd and EtOH, the concentration of non-protein SH groups decreased in the liver and kidneys in comparison to the control and Cd-exposed rats, and in the liver also in comparison to the EtOH group. Mt concentration increased in the liver and kidneys of animals exposed to a combination of Cd and EtOH, compared to the control and EtOH group, but was reduced compared to the Cd group. Combined administration of Cd and EtOH caused an increase in the concentration of total SH groups in the kidneys compared to the control, Cd and EtOH groups. A negative correlation was found between GSH concentration and malondialdehyde (MDA) levels and positive correlation between Mt and MDA. The intensity of lipid peroxidation as well as GSH and Mt concentrations influencing this process in the state of combined exposure to Cd and EtOH results both from independent actions of these substances and interactions between them. The study outcome seems to indicate that the Cd-and EtOH-induced reduction in GSH and non-protein SH groups in the liver and kidneys may be one of the mechanisms that leads to lipid peroxidation in these organs. [ABSTRACT FROM AUTHOR]

— The effects of continuous exposure to cadmium (Cd) and ethanol on Cd turnover and zinc (Zn) and copper (Cu) body status of male Wistar rats were studied. The animals received an aqueous solution of 10% (w/v) ethanol and/or 50 mg Cd/l as the only drinking fluid for 12 weeks. The concentrations of Zn, Cu and Cd in the serum (or blood), liver, kidneys, spleen, brain, heart, femoral muscle and femur as well as in 24-h urine and faeces specimens were assessed by atomic absorption spectrometry (AAS). Ethanol alone had no effect on Cd accumulation or excretion. By contrast, co-administration of ethanol with Cd influenced the turnover of this toxic metal. Long-term consumption of ethanol alone caused a decrease in femur Zn and liver Cu concentrations. Moreover, the urinary loss of both bioelements decreased, whereas their faecal excretion was increased. Exposure to Cd resulted in an increase in liver and kidney and in a decrease in femur and 24-h urine Zn concentrations. An increase in Cu concentration in the kidney and a decrease in the brain were also noted. Moreover, Cd increased the total pool of Zn in organs (kidneys, liver, spleen, heart and brain), but did not influence that of Cu. Zn concentration in the liver, kidney and spleen of rats co-exposed to Cd and ethanol were increased, but were decreased in the brain and femur, compared to controls. The concentrations of Cu in livers and brains of these rats were decreased, whereas those in kidney, spleen and heart were increased. The urinary excretion of the elements was decreased, whereas their faecal excretion was increased. Moreover, the total amount of Cu in organs decreased below the control value and that of Zn was in the normal range. These changes in Zn and Cu levels could be explained by different effects of both toxic substances, differences in bioelement intakes (due to reduced consumption of drinking solutions and food), and the modifying effect of ethanol on Cd turnover. Our results suggest that alcoholics may be more susceptible to Cd accumulation and its effects on body Zn and Cu. [ABSTRACT FROM PUBLISHER]

The present study was performed to assess the effect of short-term ethanol administration on cadmium retention and accumulation as well as on bioelement metabolism (zinc, copper, calcium, and magnesium) in rats exposed to an aqueous solution of cadmium chloride for 8 weeks. Intoxication with cadmium led to accumulation of this toxic metal, particularly in the liver and kidney, which was linked to metallothionein synthesis as well as to a disturbance in the metabolism of zinc, copper, and calcium. These effects were dependent on the level of exposure. The administration of ethanol in the final phase of cadmium treatment increased cadmium retention and accumulation in the body with simultaneous elevation in liver and kidney metallothionein concentration. Ethanol alone or with cadmium caused or intensified the cadmium-induced changes in metabolism of zinc and copper. Calcium metabolism disturbed by cadmium was not influenced by ethanol. Neither agents had any effect on magnesium metabolism. We conclude that even short-term ethanol consumption in conditions of exposure to cadmium can increase this heavy metal body burden and lead to more serious disturbances in metabolism of important elements such as zinc and copper. Cadmium- and ethanol-induced changes in the homeostasis of these microelements are probably connected with the ability of both xenobiotics to cause metallothionein induction. [ABSTRACT FROM PUBLISHER]

Objective: To study experiences of women who gave birth in maternity units that have implemented a 'care bundle' quality improvement initiative to reduce obstetric anal sphincter injury (OASI) and associated morbidity., Design: Postnatal electronic questionnaire., Setting: Twenty-nine maternity units across England, Scotland and Wales., Population: Women with live vaginal births., Methods: Descriptive statistics for quantitative results. Analysis of free-text responses informed by framework method., Main Outcome Measures: Experience with components of the care bundle: information provision, manual perineal protection (MPP) and post-birth rectal examination., Results: In this study, 1208 women completed the survey: 684 (56.6%) said they received antenatal information about perineal health, 377 (31.2%) recalled MPP, and 664 (55.0%) recalled rectal examination. Of the 684 women who said they received antenatal information, 595 (87.0%) agreed that the information was easy to understand, and 423 (61.8%) agreed that it helped them to make their own choices to reduce their OASI risk. One hundred and fifty-four (22.5%) agreed that the information made them fearful about giving birth vaginally. Of the 377 women who recalled MPP, 203 (53.9%) felt it provided them with support, and another 97 (25.7%) did not mind the sensation. Of the 664 women who recalled rectal examination, 281 (42.3%) did not mind the exam, and another 335 (50.5%) felt it was uncomfortable but understood its importance. Free-text responses aligned with quantitative results., Conclusions: Many women did not recall MPP or rectal examination. The reported experiences for those who recalled these components do not support concerns that the OASI care bundle has negative effects on women's experiences., (© 2024 The Author(s). BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Background: The objective of this study was to understand health care providers' perspectives regarding the facilitators of and barriers to the success of the former Pap and VIA-based cervical cancer program in Iquitos, Peru, using the Consolidated Framework for Implementation Research (CFIR) to inform the transition to the HPV screen-and-treat intervention. By exploring the pre-implementation organizational context, or inner setting, through the opinions of those who would implement the HPV-based intervention at the patient care level, this research lays the foundation to assess readiness before implementation and understand what's necessary to design contextually appropriate and sustainable interventions in LMIC settings., Methods: We conducted 19 semi-structured interviews with health professionals (12 nurse-midwives, 4 doctors, and 3 laboratory technicians) who administered the former Pap- and VIA-based cervical cancer EDT program., Results: Providers identified information gaps between the primary level of care, where cervical cancer screening occurs, and the hospital level of care, where diagnosis and treatment occurs. These gaps, which were caused in part by fragmented, antiquated, and overlapping data systems, resulted in the loss of patients between levels of care. Participants also noted a lack of trained personnel and basic materials. Some providers found their way around these gaps by facilitating informal information exchanges among providers to ensure women were not lost to follow-up., Conclusions: PPC relied on these findings and other data from INSPIRE Phase 1 to implement a HPV-based screen-and-treat program that dramatically increased screening and treatment; however, challenges remain regarding resources and sustainability related to HPV technology., Competing Interests: Competing Interests The authors declare that they have no other competing interests. PEG and VPS, on behalf of the Proyecto Precancer, received discounted prices and/or donated supplies from Copan and Cepheid.

Background: Cervical cancer is preventable with vaccination and early detection and treatment programs. However, for these programs to work as intended, stigma related to HPV and cervical cancer must be understood and addressed. We explored pre-existing stigma associated with HPV and cervical cancer in the public healthcare system and community of a low-resource setting prior to implementation of an HPV screen-and-treat program., Methods: This study conducted thematic analysis of data collected during implementation of a novel HPV screen-and-treat system for cervical cancer early detection and treatment in Iquitos, Peru. We included 35 semi-structured interviews (19 health professionals, 16 women with cervical precancer or cancer), eight focus groups (70 community women), one workshop (14 health professionals), 210 counseling observations (with 20 nurse-midwives), and a document review. We used the Socio-Ecological Model to organize the analysis., Results: We identified three main themes: 1. the implication that women are to blame for their HPV infection through characterizations of being easy or promiscuous, 2. the implication that men are to blame for women's HPV infections through being considered careless or unfaithful, 3. HPV is shameful, embarrassing, and something that should be hidden from others. Consequently, in some cases, women refrained from getting screened for HPV. These themes were seen at the individual level among women, relationship level among women, men, and family members, community level among healthcare staff, and societal level within components of cervical cancer guidelines and male chauvinism., Conclusions: Cervical cancer early detection and treatment programs in limited resource settings must address stigma entrenched throughout the entire healthcare system and community in order to sustainably and successfully implement and scale-up new programs. Interventions to tackle this stigma can incorporate messages about HPV infections and latency to lessen the focus on the influence of sexual behavior on HPV acquisition, and instead, promote screening and treatment as paramount preventative measures., (© 2023. The Author(s).)

Background: The study's objective was to explore the factors associated with loss to follow-up among women with abnormal cervical cancer screening results in Iquitos, Peru from women's perspectives., Methods: In-depth interviews were conducted with 20 screen-positive women who were referred for follow-up care but for whom evidence of follow-up was not found. Interview transcripts were thematically analyzed inductively, and the codes were then categorized using the Health Care Access Barriers Model for presentation of results., Results: All interviewed women were highly motivated to complete the continuum of care but faced numerous barriers along the way, including cognitive barriers such as a lack of knowledge about cervical cancer and poor communication from health professionals regarding the process, structural barriers such as challenges with scheduling appointments and unavailability of providers, and financial barriers including out-of-pocket payments and costs related to travel or missing days of work. With no information system tracking the continuum of care, we found fragmentation between primary and hospital-level care, and often, registration of women's follow-up care was missing altogether, preventing women from being able to receive proper care and providers from ensuring that women receive care and treatment as needed., Conclusions: The challenges elucidated demonstrate the complexity of implementing a successful cervical cancer prevention program and indicate a need for any such program to consider the perspectives of women to improve follow-up after a positive screening test., (© 2023. The Author(s).)

Hybrid effectiveness-implementation studies allow researchers to combine study of a clinical intervention's effectiveness with study of its implementation with the aim of accelerating the translation of evidence into practice. However, there currently exists limited guidance on how to design and manage such hybrid studies. This is particularly true for studies that include a comparison/control arm that, by design, receives less implementation support than the intervention arm. Lack of such guidance can present a challenge for researchers both in setting up but also in effectively managing participating sites in such trials. This paper uses a narrative review of the literature (Phase 1 of the research) and comparative case study of three studies (Phase 2 of the research) to identify common themes related to study design and management. Based on these, we comment and reflect on: (1) the balance that needs to be struck between fidelity to the study design and tailoring to emerging requests from participating sites as part of the research process, and (2) the modifications to the implementation strategies being evaluated. Hybrid trial teams should carefully consider the impact of design selection, trial management decisions, and any modifications to implementation processes and/or support on the delivery of a controlled evaluation. The rationale for these choices should be systematically reported to fill the gap in the literature., Competing Interests: NS is the director of the London Safety and Training Solutions Ltd, which offers training in patient safety, implementation solutions and human factors to healthcare organisations and the pharmaceutical industry. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer JM declared a shared affiliation, with no collaboration, with one of the authors, NS, to the handling editor at the time of the review., (© 2023 Jurczuk, Thakar, Carroll, Phillips, Meulen, Gurol-Urganci and Sevdalis.)

Rising rates of obstetric anal sphincter injury (OASI) led to a collaborative effort by the Royal College of Obstetricians and Gynaecologists (RCOG) and the Royal College of Midwives (RCM) to develop and evaluate the OASI Care Bundle (OASI-CB). The OASI-CB comprises four practices (antenatal discussion about OASI, manual perineal protection, mediolateral episiotomy at 60° from the midline, and systematic examination of the perineum, vagina and ano-rectum after vaginal birth) and was initially implemented as part of a quality improvement (QI) project-"OASI1"-in 16 maternity units across Great Britain. Evaluation of the OASI1 project found that the care bundle reduced OASI rates and identified several barriers and enablers to implementation. This paper summarises the key findings, including strengths, limitations and lessons learned from the OASI1 QI project, and provides rationale for further evaluation of the OASI-CB., (© 2021. The Author(s).)

Background: The Obstetric Anal Sphincter Injury (OASI) Care Bundle comprises four primary and secondary prevention practices that target the rising rates of severe perineal tearing during childbirth, which can have severe debilitating consequences for women. The OASI Care Bundle was implemented in 16 maternity units in Britain in the OASI1 project (2017-2018), which demonstrated the care bundle's effectiveness in reducing OASI rates. In OASI2, the care bundle will be scaled up to 20 additional National Health Service (NHS) maternity units in a hybrid effectiveness-implementation study that will examine the effectiveness of strategies used to introduce, implement and sustain the care bundle., Methods: OASI2 is a two-arm cluster-randomised control trial (C-RCT) of maternity units in England, Scotland and Wales, with an additional non-randomised study arm. C-RCT arm 1 (peer support, n = 10 units) will be supported by 'buddy' units to implement the OASI Care Bundle. C-RCT arm 2 (lean implementation, n = 10 units) will implement without external support. The additional study arm (sustainability, n = 10 units) will include some original OASI1 units to evaluate the care bundle's sustainability and OASI rates over time, from before OASI1 and through the end of OASI2. Units in all three study arms will receive an Implementation Toolkit with training resources and implementation support. The C-RCT arms will be compared in terms of OASI rate reduction (primary effectiveness outcome) and clinicians' adoption of the care bundle (primary implementation outcome). Clinical data will be collated from maternity information systems; implementation data will be collected through validated surveys with women and clinicians, supplemented by qualitative methods. Descriptive statistics and regression modelling will be used for analysis. Emergent themes from the qualitative data will be assessed using framework analysis., Discussion: OASI2 will study the impact of various implementation strategies used to introduce and sustain the OASI Care Bundle, and how these strategies affect the bundle's clinical effectiveness. The study will generate insights into how to effectively scale-up and sustain uptake and coverage of similar interventions in maternity units. A locally adaptable 'implementation blueprint' will be produced to inform development of future guidelines to prevent perineal trauma., Trial Registration: ISRCTN26523605.

Background: The World Health Organization (WHO) has called for a systems thinking approach to health systems strengthening to increase adoption of evidence-based interventions (EBI). The Integrative Systems Praxis for Implementation Research (INSPIRE) methodology operationalizes the WHO systems thinking framework to meet cervical cancer elimination-early detection and treatment (CC-EDT) goals., Methods: Using a systems thinking approach and grounded in the consolidated framework for implementation research, INSPIRE integrates multiple research methodologies and evaluation frameworks into a multilevel implementation strategy., Results: In phase I (creating a shared understanding), soft systems methodology and pathway analysis are used to create a shared visual understanding of the CC-EDT system, incorporating diverse stakeholder perspectives of the "what, how, and why" of system behavior. Phase II (finding leverage) facilitates active stakeholder engagement in knowledge transfer and decision-making using deliberative dialogues and multiple scenario analyses. Phase III (acting strategically) represents stakeholder-engaged implementation planning, using well-defined implementation strategies of education, training, and infrastructure development. In phase IV (learning and adapting), evaluation of key performance indicators via a reach, effectiveness, adoption, implementation, and maintenance framework is reviewed by stakeholder teams, who continuously adapt implementation plans to improve system effectiveness., Conclusions: The INSPIRE methodology is a generalizable approach to context-adapted implementation of EBIs., Impact: Replacing static dissemination of implementation "roadmaps" with learning health systems through the integration of systems thinking and participatory action research, INSPIRE facilitates the development of scalable and sustainable implementation strategies adapted to local contexts., (©2020 American Association for Cancer Research.)

Background: Live bivalve molluscs, echinoderms, tunicates and marine gastropod are referred in EU food laws, and require member states to implement official controls in classified production areas, with the monitoring and classification of those areas. If, due to contaminant tests results, a production area is closed, any product from there is prohibited to be commercialized. Mobile applications optical character recognition (OCR) functionalities could ease the access to contaminant levels and production area classifications. This study verifies what information is available in live bivalves' labels, describes an OCR algorithm for those labels and evaluates it., Methods: 86 labels were selected from four sale points in Lisbon, and photographed using smartphones. Each label was evaluated by a human to determine what data was available (either required or not). An OCR algorithm was developed and applied on the collected labels and validated against the data extracted by the human analysis., Results: The analysis shows that all the labels included the required information, and 63% of the labels included the identifier for the production zone. The label-reading algorithm performs with an accuracy of 79.85% for the individual values., Conclusion: High accuracy of the developed label-reading algorithm shows potential for providing instant automatic access to the date and production area, but is affected by the variability on the label structure. Although not required by food laws, the majority of the sampled labels included complementary information (classified production area) that will allow access to more precise information about the existing biotoxin tests and analysis results., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Public Health Association.)

It was investigated, in a female rat model of low and moderate lifetime human exposure to cadmium (Cd), whether polyphenols from Aronia melanocarpa berries (chokeberry; AMP) may offer protection from this heavy metal-induced disorders in bone metabolism. For this purpose, numerous indices of bone formation (osteocalcin, alkaline phosphatase, osteoprotegerin) and resorption (carboxy-terminal cross-linking telopeptides of type I collagen, soluble receptor activator of nuclear factor-κB ligand) in the serum and/or distal femur epiphysis (trabecular bone region), as well as bone mineral status (volumetric bone mineral density of the femur and content of mineral components, including calcium, in the bone tissue at the distal femur epiphysis) were evaluated in female Wistar rats that received a 0.1% aqueous extract of AMP, as the only drinking fluid (prepared from lyophilized extract by Adamed Consumer Healthcare), and/or Cd in diet (1 and 5mg/kg) for 3, 10, 17, and 24 months. Examination of the phytochemical profile of the aronia extract revealed high content of polyphenols (612.40 ± 3.33 mg/g), including anthocyanins, proanthocyanidins, phenolic acids, and flavonoids. Among detected compounds anthocyanins were identified as dominating. The exposure to Cd, dose- and duration-dependently, enhanced resorption and inhibited formation of the bone tissue resulting in its decreased mineralization. The administration of AMP under the exposure to 1 and 5 mgCd/kg diet provided important protection from this heavy metal-induced disturbances in the bone turnover and changes in the bone mineral status, and the beneficial impact of polyphenols resulted from their independent action and interaction with Cd. These findings suggest that consumption of Aronia melanocarpa polyphenols may play a role in prevention against female skeleton damage due to chronic exposure to Cd and that chokeberry represents the good natural plant candidate for further investigations of its prophylactic use under environmental exposure to this heavy metal., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Recently a growing attention has been paid to the possibility of using biologically active compounds, including polyphenols, for the prevention of unfavourable effects of exposure to xenobiotics. The study was aimed to investigate, in a female rat model, whether consumption of Aronia melanocarpa polyphenols (AMP) under chronic exposure to cadmium (Cd) decreases the gastrointestinal absorption and body burden of this heavy metal. For this purpose, Cd turnover (apparent absorption, retention in the body, concentration in the blood, soft tissues and bone tissue, total pool in internal organs, faecal and urinary excretion) was evaluated in the female Wistar rats who were administered only a 0.1% aqueous extract of AMP (prepared from the powdered extract containing 65.74% of polyphenols) as drinking fluid or/and Cd in diet (1 and 5 mg/kg) for up to 24 months. AMP administration under the low Cd treatment (1 mg/kg diet) had only a very slight protective impact against this metal accumulation in the organism, whereas polyphenols application under moderate exposure (5 mg Cd/kg diet) significantly decreased apparent absorption and retention in the body, and increased urinary concentration of this xenobiotic, resulting in its lower concentration in the blood and lower accumulation in soft tissues (mainly in the liver and kidneys) and bone tissue. Based on the study, it can be concluded that consumption of polyphenol- rich products may prevent Cd absorption from the diet polluted by this metal and its accumulation in the females' body, and thus also prevent its toxic action.

It was investigated whether the ability of zinc (Zn) to prevent cadmium (Cd)-induced lipid peroxidation may be connected with its impact on glutathione peroxidase (GPx) activity and selenium (Se) concentration. GPx and Se were determined in the serum, liver and kidney of the rats that received Cd (5 or 50 mg/L) or/and Zn (30 mg/L) in drinking water for 6 months in whose the protective Zn impact was noted (Rogalska J, Brzóska MM, Roszczenko A, Moniuszko-Jakoniuk J. Enhanced zinc consumption prevents cadmium-induced alterations in lipid metabolism in male rats. Chem Biol Interact 2009;177:142-52). Moreover, dependences between these parameters, and indices of lipid peroxidation (F(2)-isoprostane, lipid peroxides, oxidized low density lipoprotein cholesterol) as well as concentrations of Cd and Zn were estimated. The supplementation with Zn during the exposure to 5 mg Cd/L entirely antagonized the Cd-induced increase in GPx activity and Se concentration in the liver and kidney, but not in the serum. Zn administration during the treatment with 50 mg Cd/L totally or partially prevented from the Cd-caused decrease in GPx activity and Se concentration in the serum, liver and kidney. At the higher level of Cd exposure, GPx activity in the serum and tissues positively correlated with Se concentration. Moreover, numerous correlations were noted between GPx and/or Se and the indices of lipid peroxidation. The results indicate that the protective impact of Zn against the Cd-induced lipid peroxidation during the relatively high exposure might be connected with its beneficial influence on Se concentration and GPx activity in the serum and tissues, whereas this bioelement influence at the moderate exposure seems to be independent of GPx and Se., (Copyright © 2011 Elsevier GmbH. All rights reserved.)

The study was aimed to estimate whether rat's exposure to cadmium (Cd; 50mg/l in drinking water for 12 weeks) and/or ethanol (EtOH; 5g/kg b.wt./24h p.o. for 12 weeks), noted by us to induce oxidative stress and stimulate lipid peroxidation, can cause oxidative damage to proteins and DNA, and whether and to what extent the effects of co-exposure differ from those observed under the treatment with each substance alone. Protein carbonyl groups (PC) and protein thiol groups (PSH) in the serum, liver and kidney, as markers of oxidative protein damage, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the serum, as a marker of DNA oxidation, were determined. The exposure to Cd or/and EtOH led to oxidative protein damage (increased PC and decreased PSH concentrations in the serum and/or liver), and to DNA oxidation (increased 8-OHdG concentration in the serum). The effects were more advanced at the co-exposure than at the treatment with each substance alone. The more serious damage to proteins and DNA at the co-exposure to Cd and EtOH seems to be the effect of independent action of both xenobiotics. The results of the present paper together with our recent findings in the same rats seem to indicate that at co-exposure to Cd and EtOH proteins and DNA may be more vulnerable to oxidation than lipids. The paper is the first report suggesting that excessive EtOH consumption during exposure to Cd may increase the risk of health damage via enhancing protein and DNA oxidation.

The present study was aimed at estimate, based on the rat model of human moderate and relatively high chronic exposure to cadmium (Cd), whether zinc (Zn) supplementation may prevent Cd-induced weakening in the bone biomechanical properties. For this purpose, male Wistar rats were administered Cd (5 or 50 mg/l) or/and Zn (30 or 60 mg/l) in drinking water for 6 and 12 months. Bone mineral density (BMD) and biomechanical properties (yield load, ultimate load, post-yield load, displacement at yield and at ultimate, stiffness, work to fracture, yield stress, ultimate stress and Young modulus of elasticity) of the femoral distal end and femoral diaphysis were examined. Biomechanical properties of the distal femur were estimated in a compression test, whereas those of the femoral diaphysis -- in a three-point bending test. Exposure to Cd, in a dose and duration dependent manner, decreased the BMD and weakened the biomechanical properties of the femur at its distal end and diaphysis. Zn supplementation during Cd exposure partly, but importantly, prevented the weakening in the bone biomechanical properties. The favorable Zn influence seemed to result from an independent action of this bioelement and its interaction with Cd. However, Zn supply at the exposure to Cd had no statistically significant influence on the BMD at the distal end and diaphysis of the femur. The results of the present paper suggest that Zn supplementation during exposure to Cd may have a protective influence on the bone tissue biomechanical properties, and in this way it can, at least partly, decrease the risk of bone fractures. The findings seem to indicate that enhanced dietary Zn intake may be beneficial for the skeleton in subjects chronically exposed to Cd.

The aim of the present study is to investigate, based on the rat model of moderate and relatively high human exposure to cadmium (Cd), whether zinc (Zn) supplementation may prevent Cd-induced disorders in bone metabolism. For this purpose, male Wistar rats received Cd (5 and 50mg/l) or/and Zn (30 and 60mg/l) in drinking water for 6 and 12 months. Bone densitometry and biochemical markers of bone turnover were used to assess the effects of Cd or/and Zn. Bone mineral content (BMC) and density (BMD) were measured in the femur. Serum osteocalcin (OC) and alkaline phosphatase in trabecular (bT-ALP) and cortical (bC-ALP) bone were determined as bone formation markers, and carboxy-terminal cross-linking telopeptides of type I collagen (CTX) in serum were measured as bone resorption marker. Serum concentration of calcium (Ca) and its renal handling, as well as Zn and Cd concentrations in the serum/blood, urine and femur were evaluated as well. The exposure to 5 and 50mg Cd/l (0.340+/-0.026 and 2.498+/-0.093mg Cd/kg body wt/24h, respectively), in a dose and duration dependent manner, affected bone turnover (inhibited bone formation and stimulated its resorption) and disturbed bone mineralization (decreased BMC, BMD and Zn concentration). Zn supply at the concentration of 30 and 60mg/l (1.904+/-0.123 and 3.699+/-0.213mg/kg body wt/24h, respectively) during Cd exposure influenced the Cd-induced disorders in bone metabolism. Zn administration to the Cd-exposed rats enhanced the bone ALP activity and prevented Cd-induced bone resorption, but had no statistically significant effect on BMC and BMD; however, mean values of the densitometric parameters in the rats receiving both Cd and Zn were higher than in those treated with Cd alone. Moreover, Zn supplementation at both levels of Cd exposure was found to prevent Cd accumulation in the femur and the Cd-induced decrease in bone Zn concentration. The results of the present study allow the conclusion that Zn supplementation during Cd exposure may partly protect from disorders in bone metabolism. The influence of Zn may be accompanied by its ability to prevent Cd-induced Zn deficiency and to decrease Cd accumulation in bone tissue. The findings seem to indicate that enhanced dietary intake of Zn in subjects chronically exposed to moderate and relatively high Cd levels may have a protective influence on the skeleton.

The involvement of low-molecular thiols, such as reduced glutathione (GSH) and metallothionein (Mt), in the mechanisms of the peroxidative action of lead (Pb) and ethanol (EtOH) in liver and kidney was investigated on rats treated with 500 mg Pb/l (in drinking water) and 5 g EtOH/kg body wt./24h (p.o.), alone and in conjunction with each other for 12 weeks. Beside of GSH and Mt, concentration of total and non-protein SH groups (TSH and NPSH, respectively) in these organs as well as the blood activity of dehydratase of delta-aminolevulinic acid (delta-ALAD) and the urinary concentration of delta-aminolevulinic acid (delta-ALA) were determined. The exposure to Pb and EtOH alone and in conjunction with each other led to a decrease in the blood delta-ALAD activity and an increase in the urinary delta-ALA concentration, and these effects were more markedly advanced at co-exposure. In the liver and kidney of rats treated with Pb and/or EtOH, a decrease in concentrations of GSH and NPSH was noted, compared to control. However, in the Pb+EtOH group, only the liver concentrations of NPSH and GSH were lower also compared to the Pb and EtOH groups. The liver concentration of TSH decreased in the rats exposed to EtOH alone and in conjunction with Pb, whereas the kidney concentration of TSH decreased only at co-exposure to Pb and EtOH. Mt concentration was unchanged except for an increase in the liver in the Pb and Pb+EtOH groups. Two-way analysis of variance (ANOVA/MANOVA) revealed that the changes noted at the co-exposure to Pb and EtOH resulted from an independent action of the two xenobiotics as well as from their interactive action. Negative correlations noted between the liver and kidney concentrations of GSH and/or NPSH and recently reported malondialdehyde (MDA, an indicator of lipid peroxidation) concentration in both organs of those rats indicate the relationship between the content of SH groups and the intensity of the Pb and/or EtOH-induced lipid peroxidation. The results allow for the conclusion that the decrease in the liver and kidney concentrations of GSH and NPSH are involved in the mechanisms of the peroxidative action of Pb and EtOH alone and at co-exposure in these organs.