RESUMO
Importance: Physicians are exposed to high stress and strain that results in burnout, which affects them, their families, their patients, and the entire health care system; thus, there is an urgent need to develop methods to increase the resiliency of physicians. Sudarshan Kriya Yoga (SKY) is a comprehensive yoga breathing and meditation-based program that is a potential approach to mitigate physician burnout. Objective: To determine whether SKY can reduce psychological distress and improve wellness in physicians. Design, Setting, and Participants: This randomized clinical trial assessed the potential efficacy of SKY compared with a stress management education (SME) training as control. This study was conducted online from November 11, 2021, to March 14, 2022, and included physicians from Turkey, Germany, and Dubai. Both the SKY and the SME control groups received 1.5 hours of training for 3 consecutive days via a group video conference call. Participants were physicians willing to do some form of relaxation exercise everyday for 2 months. Exclusion criteria included presence of major illness and maintaining a regular mind-body program practice. Statistical analysis took place from March to November 2023. Interventions: Participants were randomly assigned 1:1 into 2 groups-the SKY group or the SME (control) group-using a computer algorithm. After the 3-day instruction period, the participants in the SKY group practiced for approximately 30 minutes per day on their own and participated in a weekly 1-hour, group-based online follow-up practice. After the 3-day instruction period, participants in the SME group reviewed and applied the notes from stress management education training at their initiative and had a weekly 1-hour group-based online follow-up session. Main Outcomes and Measures: The primary outcomes were stress and depression (measured by the 42-item Depression, Anxiety, and Stress Scale [DASS-42]) and insomnia measured by the Regensburg Insomnia Scale (RIS) with primary end point at 8 weeks. Secondary outcomes included anxiety (DASS-42); optimism (Life Orientation Test-Revised [LOT-R]); professional fulfillment, work exhaustion, interpersonal disengagement, and overall burnout (Professional Fulfillment Index [PFI]); and self-reported professional errors (Self-Reported Professional Error Questionnaire). Results: This study included 129 participants (SME, 63 participants [48.9%]; SKY, 66 participants [51.1%]; 115 females [89.2%]; 14 males [10.8%]; mean [SD] age, 46.2 [9.0] years). Compared with the SME control group, participants in the SKY group had significantly decreased stress on the DASS-42 at posttraining (difference, -6.8 points; 95% CI, -9.6 to -4.1 points; P = .006) and at postintervention (difference, -6.0 points; 95% CI, -8.8 to -3.3 points; P = .03), significantly decreased depression at posttraining (difference, -5.7 points; 95% CI, -8.6 to -2.8 points; P < .001) and postintervention (difference, -5.4 points; 95% CI, -8.3 to -2.5 points; P < .001), and significantly decreased anxiety at postintervention. In addition, there was a significant decrease in insomnia from baseline to postintervention in the SKY group (difference, -0.3 points; 95% CI, -2.3 to 1.7 points; P = .01). The SKY group also showed significantly increased professional fulfillment as well as significant decreases in work exhaustion, interpersonal disengagement, and burnout. There was no effect on self-reported medical errors. Conclusions and Relevance: In this randomized clinical trial, physicians who regularly practiced SKY throughout a 2-month period experienced improvements in wellness and decreased burnout. These data suggest that SKY may be an effective, practical, and safe strategy to increase wellness and mitigate burnout in physicians. Trial Registration: ClinicalTrials.gov Identifier: NCT05956470.
Assuntos
Meditação , Distúrbios do Início e da Manutenção do Sono , Yoga , Feminino , Masculino , Humanos , Pessoa de Meia-Idade , Esgotamento Psicológico , RespiraçãoRESUMO
Various aspects of the in vitro culture conditions can impact the functional response of immune cells. For example, it was shown that a Ca2+ concentration of at least 1.5 mM during in vitro stimulation is needed for optimal cytokine production by conventional αß T cells. Here we extend these findings by showing that also unconventional T cells (invariant Natural Killer T cells, mucosal-associated invariant T cells, γδ T cells), as well as B cells, show an increased cytokine response following in vitro stimulation in the presence of elevated Ca2+ concentrations. This effect appeared more pronounced with mouse than with human lymphoid cells and did not influence their survival. A similarly increased cytokine response due to elevated Ca2+ levels was observed with primary human monocytes. In contrast, primary human monocyte-derived macrophages, either unpolarized (M0) or polarized into M1 or M2 macrophages, displayed increased cell death in the presence of elevated Ca2+ concentrations. Furthermore, elevated Ca2+ concentrations promoted phenotypic M1 differentiation by increasing M1 markers on M1 and M2 macrophages and decreasing M2 markers on M2 macrophages. However, the cytokine production of macrophages, again in contrast to the lymphoid cells, was unaltered by the Ca2+ concentration. In summary, our data demonstrate that the Ca2+ concentration during in vitro cultures is an important variable to be considered for functional experiments and that elevated Ca2+ levels can boost cytokine production by both mouse and human lymphoid cells.
Assuntos
Cálcio , Macrófagos , Humanos , Cálcio/metabolismo , Macrófagos/metabolismo , Citocinas/metabolismo , Monócitos/metabolismo , Diferenciação Celular , Linfócitos/metabolismoRESUMO
Macrophages are highly plastic cells that can polarize into functionally distinct subsets in vivo and in vitro in response to environmental signals. The development of protocols to model macrophage polarization in vitro greatly contributes to our understanding of macrophage biology. Macrophages are divided into two main groups: Pro-inflammatory M1 macrophages (classically activated) and anti-inflammatory M2 macrophages (alternatively activated), based on several key surface markers and the production of inflammatory mediators. However, the expression of these common macrophage polarization markers is greatly affected by the stimulation time used. Unfortunately, there is no consensus yet regarding the optimal stimulation times for particular macrophage polarization markers in in vitro experiments. This situation is problematic, (i) as analysing a particular marker at a suboptimal time point can lead to false-negative results, and (ii) as it clearly impedes the comparison of different studies. Using human monocyte-derived macrophages (MDMs) in vitro, we analysed how the expression of the main polarization markers for M1 (CD64, CD86, CXCL9, CXCL10, HLA-DR, IDO1, IL1ß, IL12, TNF), M2a (CD200R, CD206, CCL17, CCL22, IL-10, TGM2), and M2c (CD163, IL-10, TGFß) macrophages changes over time at mRNA and protein levels. Our data establish the most appropriate stimulation time for the analysis of the expression of human macrophage polarization markers in vitro. Providing such a reference guide will likely facilitate the investigation of macrophage polarization and its reproducibility.
Assuntos
Interleucina-10 , Ativação de Macrófagos , Biomarcadores/metabolismo , Humanos , Interleucina-10/metabolismo , Macrófagos/metabolismo , Reprodutibilidade dos TestesRESUMO
Regulatory B cells (Bregs) play a crucial role in immunological tolerance primarily through the production of IL-10 in many diseases including autoimmune disorders, allergy, infectious diseases, and cancer. To date, various Breg subsets with overlapping phenotypes have been identified. However, the roles of Bregs in Helicobacter infection are largely unknown. In the present study, we investigate the phenotype and function of Helicobacter -stimulated B cells. Our results demonstrate that Helicobacter felis -stimulated IL-10- producing B cells (Hfstim- IL-10+ B) are composed of B10 and Transitional 2 Marginal Zone Precursor (T2-MZP) cells with expression of CD9, Tim-1, and programmed death 1 (PD-1). On the other hand, Helicobacter felis -stimulated IL-10- nonproducing B (Hfstim- IL-10- B) cells are mainly marginal zone (MZ) B cells that express PD-L1 and secrete TGF-ß, IL-6, and TNF-α, and IgM and IgG2b. Furthermore, we show that both Hfstim- IL-10+ B cells and Hfstim- IL-10- B cells induce CD49b+LAG-3+ Tr1 cells. Here, we describe a novel mechanism for PD-1/PD-L1- driven B cell-dependent Tr1 cell differentiation. Finally, we explore the capability of Hfstim- IL-10- B cells to induce Th17 cell differentiation, which we find to be dependent on TGF-ß. Taken together, the current study demonstrates that Hfstim- B cells induce Tr1 cells through the PD-1/PD-L1 axis and Th17 cells by secreting TGF-ß.
Assuntos
Subpopulações de Linfócitos B/imunologia , Infecções por Helicobacter/imunologia , Ativação Linfocitária/imunologia , Subpopulações de Linfócitos T/imunologia , Animais , Antígeno B7-H1/imunologia , Diferenciação Celular/imunologia , Helicobacter felis , Camundongos , Camundongos Endogâmicos C57BL , Receptor de Morte Celular Programada 1/imunologiaRESUMO
BACKGROUND: Nitric oxide (NO) seems to play an important role during renal ischemia/reperfusion (I/R) injury. We investigated whether rutin inhibits inducible nitric oxide synthase (iNOS) and reduces 3-nitrotyrosine (3-NT) formation in the kidneys of rats during I/R. METHODS: Wistar albino rats were nephrectomized unilaterally and, 2 weeks later, subjected to 45 minutes of left renal pedicle occlusion followed by 3 hours of reperfusion. We intraperitoneally administered L-N6-(1-iminoethyl)lysine (L-NIL; 3 mg/kg) for 30 minutes or rutin (1 g/kg) for 60 minutes before I/R. After reperfusion, kidney samples were taken for immunohistochemical analysis of iNOS and 3-NT. We measured plasma nitrite/nitrate and cyclic guanosine monophosphate (cGMP) to evaluate NO levels. RESULTS: Ischemia/reperfusion caused plasma cGMP to increase significantly. Similarly, plasma nitrite/nitrate was elevated in the I/R group compared with the control group. Histochemical staining was positive for iNOS and 3-NT in the I/R group. Pretreatment with L-NIL or rutin significantly mitigated the elevation of plasma cGMP and nitrite/nitrate. These changes in biochemical parameters were also associated with changes in immunohistochemical appearance. Pretreatment with L-NIL or rutin significantly decreased the incidence and severity of iNOS and 3-NT formation in the kidney tissues. CONCLUSION: Our findings suggest that high activity of iNOS causes renal I/R injury, and that rutin exerts protective effects, probably by inhibiting iNOS.
Assuntos
Inibidores Enzimáticos/farmacologia , Rim/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Substâncias Protetoras/farmacologia , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Rutina/farmacologia , Tirosina/análogos & derivados , Animais , Biomarcadores/sangue , GMP Cíclico/sangue , Inibidores Enzimáticos/administração & dosagem , Imuno-Histoquímica , Infusões Parenterais , Rim/enzimologia , Rim/metabolismo , Lisina/análogos & derivados , Lisina/farmacologia , Masculino , Nefrectomia , Nitratos/sangue , Óxido Nítrico Sintase Tipo II/metabolismo , Nitritos/sangue , Substâncias Protetoras/administração & dosagem , Ratos , Ratos Wistar , Traumatismo por Reperfusão/enzimologia , Rutina/administração & dosagem , Tirosina/efeitos dos fármacos , Tirosina/metabolismoRESUMO
The aim of this study was to investigate whether bisphenol A (BPA), nonylphenol (NP), and octylphenol (OP) induce oxidative stress on the kidney tissue of male rats and whether coadministration of vitamin C, an antioxidant, can prevent any possible oxidative stress. The Wistar male rats were divided into seven groups, including control, BPA, NP, OP, BPA+C, NP + C, OP +C. BPA, NP, and OP (25 mg/kg/day) was administered alone; vitamin C (60 mg/kg/day) was administered along with BPA, OP, and NP to the rats for 50 days. There was a decrease in serum concentration of blood urea nitrogen (BUN) in NP and OP groups compared with control group. Vitamin C coadministration with BPA, NP, and OP did not produce significant increase in BUN concentration in BPA +C, NP+ C, and OP + C group as compared with BPA, NP, and OP groups, respectively. The lowest serum creatinine activity and the highest lactate dehydrogenase (LDH) activity was present in kidney of BPA+C, NP+C and OP+C groups compared with BPA, NP, and OP groups. The malondialdehyde (MDA) levels were significantly higher while glutathione (GSH) levels were lower in treatment groups than controls. Furthermore, an increase was observed in MDA levels whereas a decrease was observed in GSH levels in BPA+ C, NP + C, and OP+ C groups compared with BPA, NP, and OP groups, respectively. These finding are in accordance with immunohistochemical staining of MDA and GSH. Histopathological examination of the kidneys of rats in BPA, OP, NP, BPA+ C, NP + C, and OP+ C groups revealed necrotic lesions, congestion, and mononuclear cell infiltration. In conclusion BPA, NP, and OP might induce oxidative damage in kidney of rats. In addition, coadministration of vitamin C with BPA, NP, and OP to male rats augments this damage in the kidney of male rats.
Assuntos
Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Disruptores Endócrinos/toxicidade , Rim/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fenóis/toxicidade , Animais , Compostos Benzidrílicos , Peso Corporal/efeitos dos fármacos , Catalase/metabolismo , Creatinina/sangue , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Rim/metabolismo , Rim/patologia , Masculino , Malondialdeído/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Wistar , Albumina Sérica/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
The purpose of this study was to investigate whether bisphenol A (BPA), nonylphenol (NP) and octylphenol (OP) induce oxidative stress in the liver of male rats and co-administration of vitamin C can prevent any possible oxidative stress. Wistar male rats were divided into seven groups (vehicle, BPA, NP, OP, BPA+C, NP+C, OP+C). BPA, OP and NP groups (25 mg kg(-1)day(-1)) were administered orally to rats three times a week for 50 days. In BPA+C, NP+C, OP+C groups, vitamin C (60 mg kg(-1)day(-1)) was administered along with BPA, OP and NP (25 mg kg(-1)day(-1)) treatments. Aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), thiobarbituric acid-reactive substances (TBARS) were increased, glutathione (GSH) levels were decreased in treatment groups. AST, ALT, LDH and TBARS levels were increased whereas GSH levels were decreased in BPA+C, NP+C and OP+C groups compared to BPA, NP, and OP groups, respectively. Hepatic necrosis and congestion were observed in livers of rats treated. In conclusion, the present results demonstrate that BPA, NP, and OP cause oxidative damage by disturbing the balance between ROS and antioxidant defenses system in liver of male rats. Vitamin C co-administration along with BPA, NP, OP aggravates the damage in liver of male rats.
Assuntos
Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Fígado/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fenóis/toxicidade , Animais , Compostos Benzidrílicos , Contagem de Células Sanguíneas , Análise Química do Sangue , Peso Corporal/efeitos dos fármacos , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Tamanho do Órgão/efeitos dos fármacos , Fenóis/antagonistas & inibidores , Ratos , Ratos Wistar , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
Reactive oxygen species (ROS) are suggested to participate in ischemia/reperfusion (I/R) injury in the kidney. This study was designed to investigate the effect of rutin, a bioflavonoid, in I/R induced renal injury. Wistar albino rats were unilaterally nephrectomized, and 2 wk later they were subjected to 45 min of left renal pedicle occlusion followed by 3h of reperfusion. Either rutin (1g/kg) or saline was administrated (i.p.) 1h prior to ischemia. At the end of the reperfusion period, kidney samples were taken for determination of renal malondialdehyde (MDA) and glutathione (GSH) levels, manganese-superoxide dismutase (MnSOD) activity and histological examination. Serum creatinine, blood urea nitrogen (BUN), and lactate dehydrogenase (LDH) concentrations were measured for the evaluation of renal function. I/R caused a significant decrease in GSH level and MnSOD activity, which was accompanied by a significant increase in MDA level of kidney tissues. Similarly, serum BUN and creatinine levels, as well as LDH were elevated in the I/R group compared with the control group. Pretreatment of rats with rutin (1g/kg/ i.p.) significantly attenuated renal dysfunction, reduced elevated MDA levels, and restored the depleted MnSOD activity and GSH levels. These beneficial changes in the biochemical parameters were also associated with parallel changes in histopathological appearance. These findings suggest that ROS play a causal role in I/R induced renal injury, and that rutin exerts renal-protective effects, probably by inhibiting ROS and antioxidant activities.
Assuntos
Nefropatias/patologia , Traumatismo por Reperfusão/prevenção & controle , Rutina/uso terapêutico , Animais , Nitrogênio da Ureia Sanguínea , Creatinina/metabolismo , Glutationa/metabolismo , Nefropatias/metabolismo , Nefropatias/prevenção & controle , Nefropatias/cirurgia , L-Lactato Desidrogenase/sangue , Peroxidação de Lipídeos , Masculino , Malondialdeído/metabolismo , Necrose , Nefrectomia , Estresse Oxidativo , Ratos , Ratos Wistar , Reperfusão , Superóxido Dismutase/metabolismoRESUMO
This study was performed to investigate whether bisphenol A (BPA), nonylphenol (NP), and octylphenol (OP) induce oxidative stress on the reproductive tract of male rats and if coadministration of vitamin C can prevent any possible oxidative stress. Wistar male rats were divided into seven groups as control (vehicle; olive oil), BPA, NP, OP, BPA+C, NP+C, and OP+C. BPA, OP, and NP groups (25 mg/kg/day) were administered orally to rats three times a week for 45 days. In BPA+C, NP+C, and OP+C groups, vitamin C (60 mg/kg/day) was administered orally along with BPA, OP, and NP (25 mg/kg/day) treatments. Malondialdehyde (MDA) appeared at significantly higher concentrations in BPA-, NP-, and OP-treated groups, when compared to control group. No significant decrease was observed in testes MDA levels of vitamin C coadministrated groups, compared with BPA, NP, and OP treatment groups. Decreased levels of reduced glutathione (GSH) were found in testes of BPA-, NP-, OP-treated rats. No significant increase was observed in testes GSH levels of BPA+C, NP+C, and OP+C groups, compared with BPA, NP, and OP treatment groups. Histological examination showed that vitamin C coadministrated groups had much more congestion areas, atrophy, and germinal cell debris in testes than those observed in other groups. Abnormal sperm percentages of BPA, BPA+C, NP+C, and OP+C groups were increased. In conclusion, the present results demonstrated that BPA, NP, and OP generate reactive oxygen species that cause oxidative damage in testes of rats. Coadministration of vitamin C aggravates this damage.
Assuntos
Ácido Ascórbico/farmacologia , Fenóis/toxicidade , Espécies Reativas de Oxigênio/farmacologia , Testículo/efeitos dos fármacos , Administração Oral , Animais , Compostos Benzidrílicos , Peso Corporal/efeitos dos fármacos , Quimioterapia Combinada , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/fisiologia , Masculino , Malondialdeído/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Próstata/efeitos dos fármacos , Próstata/patologia , Ratos , Ratos Wistar , Glândulas Seminais/efeitos dos fármacos , Glândulas Seminais/patologia , Contagem de Espermatozoides , Espermatozoides/efeitos dos fármacos , Espermatozoides/patologia , Testículo/metabolismoRESUMO
There is increasing evidence to suggest that toxic oxygen radicals play an essential role in the pathogenesis of ischemia/reperfusion (I/R) injury in the kidney. This study was designed to investigate the effects of ascorbic acid (AA) in I/R-induced renal injury in rats. Thirty two male Sprague-Dawley rats were divided equally into four groups: group 1 (control; dissection of the right renal pedicle without nephrectomy), group 2 (sham operated; unilateral nephrectomy), group 3 (I/R; unilateral nephrectomy + I/R); and group 4 (AA+I/R; unilateral nephrectomy and I/R treated with ascorbic acid, 250mg kg(-1) i.p., for one hour prior to ischemia). On the 15th day following nephrectomy, groups 3 and 4 were subjected to 45 min of renal pedicle occlusion followed by 3 h of reperfusion. At the end of the treatment period, kidney samples were taken for histological examination or determination of the renal malondialdehyde (MDA) and glutathione (GSH) levels. Serum creatinine, blood urea nitrogen (BUN), and lactate dehydrogenase (LDH) concentrations were measured for the evaluation of renal function. I/R caused a significant decrease in GSH level, which was accompanied with a significant increase in MDA level of kidney tissues. Similarly, serum BUN and creatinine levels, as well as LDH, were elevated in the I/R group as compared to the control group. In group four, AA treatment reversed all the changes in these biochemical indices, as well as histopathological alterations normally induced by I/R. The findings imply that reactive oxygen species play a causal role in I/R-induced renal injury, and that AA exerts renoprotective effects, probably by radical scavenging and antioxidant activities.
Assuntos
Injúria Renal Aguda/prevenção & controle , Antioxidantes/uso terapêutico , Ácido Ascórbico/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/patologia , Animais , Nitrogênio da Ureia Sanguínea , Glutationa/metabolismo , Peroxidação de Lipídeos/fisiologia , Masculino , Malondialdeído/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologiaRESUMO
N-ethylmaleimide (NEM) is a sulphydryl blocker which impairs the sulphydryl dependent antioxidant system (mainly glutathione) in the body by alkylating endogenous sulphydryls. This study was designed to investigate the effects of Anzer honey on NEM-induced liver injury in rats. Thirty female Wistar albino rats were divided equally into three groups. Group 1: control; Group 2: NEM; Group 3: Anzer honey+NEM. NEM (0.075mg kg(-1)) was given to both group 2 and 3 administered subcutaneously (s.c.) for 30 days. The animals in the Anzer honey+NEM group were treated with Anzer honey at a dose of 0.275g kg(-1), (p.o.) at 1h prior to every NEM injection. At the end of the 30 day treatment period, liver samples were taken for determination of the glutathione levels and histological examination. NEM treatment alone caused a significant reduction of the liver glutathione levels in group 2. Furthermore, NEM treatment caused congestion and mononuclear cell infiltration in the liver when compared to the control group. In group 3, Anzer honey treatment reversed all the changes in glutathione level, as well as histopathological alterations, normally induced by NEM. The findings imply that depletion of glutathione concentration plays a causal role in NEM-induced liver injury, and that the hepatoprotective effect of Anzer honey may be mediated through sulfhydryl-sensitive processes. They further imply that it may also possess antioxidant properties.
Assuntos
Antioxidantes/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Etilmaleimida/toxicidade , Mel , Fígado/efeitos dos fármacos , Reagentes de Sulfidrila/toxicidade , Animais , Antioxidantes/análise , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Feminino , Glutationa/metabolismo , Mel/análise , Fígado/metabolismo , Fígado/patologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismoRESUMO
Bisphenol A (BPA), nonylphenol (NP) and octylphenol (OP) are endocrine-disrupting chemicals that has been shown to exert both toxic and estrogenic effects on mammalian cells. The aim of this study was to investigate if BPA, NP and OP induce oxidative stress on the brain tissue of male rats and if co-administration of vitamin C, an antioxidant, can prevent any possible oxidative stress. The male rats were divided into seven groups as control (vehicle), BPA, NP, OP, BPA+C, NP+C, OP+C. BPA, OP and NP (25 mg/(kg day)) were administrated orally to male Wistar rats for 45 days. In vitamin C co-administration groups (BPA+C, NP+C, OP+C), vitamin C (60 mg/(kg day)) were administrated orally along with BPA, OP and NP (25 mg/(kg day)) treatments. The rats in the control group received olive oil orally. The final body and absolute organ weights of treated rats did not show any significant difference when compared with the control group. Also, there were no significant difference in relative organ weights of BPA, NP, OP, BPA+C and NP+C groups when compared with control group. Only, relative organ weights were increased significantly in OP+C group compared with control group. Decreased levels of reduced glutathione (GSH) were found in the brains of BPA, NP, OP treated rats. The end product of lipid peroxidation, malondialdehyde (MDA), appeared at significantly higher concentrations in the BPA, NP, and OP treated groups when compared to the control group. On the other hand, there were no changes in the brain MDA and GSH levels of BPA+C, NP+C and OP+C groups compared with BPA, NP and OP treatment groups, respectively. In histopathologic examination, the vitamin C co-administrated groups had much more hyperchromatic cells in the brain cortex than that observed in the groups treated with only BPA, NP, and OP. The results of this study demonstrate that BPA, NP and OP generate reactive oxygen species that caused oxidative damage in the brain of male rats. In addition, vitamin C co-administration along with BPA, NP, and OP aggravates this oxidative damage in the brain of rats.