RESUMEN
Bisphenol-A (BPA) is widely used in food packaging and household products, leading to daily human exposure and potential health risks including metabolic diseases like type 2 diabetes mellitus (T2DM). Understanding BPA's mechanisms and developing intervention strategies is urgent. Centella asiatica, a traditional herbal medicine containing pentacyclic triterpenoids, shows promise due to its antioxidant and anti-inflammatory properties, utilized for centuries in Ayurvedic therapy. We investigated the effect of Centella asiatica (CA) ethanol extract on BPA-induced pancreatic islet toxicity in male Swiss albino mice. BPA administration (10 and 100 µg/kg body weight, twice daily) for 21 days caused glucose homeostasis disturbances, insulin resistance, and islet dysfunction, which were partially mitigated by CA supplementation (200 and 400 mg/kg body weight). Additionally, heightened oxidative stress, elevated levels of proinflammatory cytokines, loss of mitochondrial membrane potential (MMP), abnormal cell cycle, and increased apoptosis were implicated in the detrimental impact of BPA on the endocrine pancreas which were effectively counteracted by CA supplementation. In summary, CA demonstrated a significant ability to mitigate BPA-induced apoptosis, modulate redox homeostasis, alleviate inflammation, preserve MMP, and regulate the cell cycle. As a result, CA emerged as a potent agent in neutralizing the diabetogenic effects of BPA to a considerable extent.
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Centella , Diabetes Mellitus Tipo 2 , Islotes Pancreáticos , Fenoles , Ratones , Animales , Masculino , Humanos , Diabetes Mellitus Tipo 2/inducido químicamente , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Islotes Pancreáticos/metabolismo , Antioxidantes/farmacología , Antioxidantes/metabolismo , Compuestos de Bencidrilo/farmacología , Peso CorporalRESUMEN
The estrogenic impact of Bisphenol-A (BPA), a widely recognized endocrine disruptor, causes disruption of pancreatic ß-cell function through estrogen receptors (ERs). While BPA's binding affinity for ERs is significantly lower than that of its natural counterpart, estrogen, recent observations of BPA's affinity for aryl hydrocarbon receptor (AhR) in specific cellular contexts have sparked a specific question: does AhR play a role in BPA's toxicological effects within the endocrine pancreas? To explore this question, we investigated BPA's (10 and 100 µg/ kg body weight/day for 21 days) potential to activate AhR within pancreatic islets and assessed the protective role of ethanol extract of Centella asiatica (CA) (200 and 400 mg/kg body weight/day for 21 days) against BPA-mediated toxicity in mouse model. Our results indicate that BPA effectively triggers the activation of AhR and modulates its target genes within pancreatic islets. In contrast, CA activates AhR but directs downstream pathways differentially and activates Nrf2. Additionally, CA was observed to counteract the disruption caused by BPA in glucose homeostasis and insulin sensitivity. Furthermore, BPA-induced oxidative stress and exaggerated production of proinflammatory cytokines were effectively counteracted by CA supplementation. In summary, our study suggests that CA influenced AhR signaling to mitigate the disrupted pancreatic endocrine function in BPA exposed mice. By shedding light on how BPA interacts with AhR, our research provides valuable insights into the mechanisms involved in the diabetogenic actions of BPA.
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Centella , Islotes Pancreáticos , Ratones , Animales , Receptores de Hidrocarburo de Aril/metabolismo , Centella/metabolismo , Homeostasis , Compuestos de Bencidrilo/toxicidad , Compuestos de Bencidrilo/metabolismo , Glucosa/metabolismo , Peso CorporalRESUMEN
Bisphenol A (BPA) is an endocrine disrupting chemical which poses great concern because of its high proportionate industrial production, omnipresent human exposure and budding toxic consequences in human. A plethora of previous studies has connected BPA to a variety of negative health outcomes and diabetes mellitus is among the first bencher. However, there is disagreement over the degree of toxic effects generated by low and high doses of BPA and critical period of exposure. Furthermore, the safe level of BPA determined by classical toxicological studies does not protect pancreatic islet cells from low dose effects of BPA. Thus, the extremities of toxic effects on pancreatic islets associated with BPA exposure are complicated and contentious. In this review, we highlighted different cellular and molecular pathways targeted by BPA to mediate its action on pancreatic islets with consideration of both low and high dose effects. Besides estrogen receptor α and ß, BPA also uses non canonical membrane bound estrogen receptor and G-protein coupled estrogen receptor to confer its toxic effects. In doing so, BPA modulates ion channels, and transcription factors; causes aggregation of human islet amyloid polypeptide, endoplasmic reticulum and mitochondrial stress; and results in activation of NFκB in pancreatic ß cells. BPA also renders a major shift in ß to α cell ratio in islets causing deregulated glucagon secretion. Hence, understanding of various mechanisms of BPA action on the pancreatic islets will provide meaningful insights in recognizing the risk posed by exposure to low and high doses of BPA.
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Islotes Pancreáticos , Receptores de Estrógenos , Compuestos de Bencidrilo/toxicidad , Humanos , Fenoles/farmacología , Receptores de Estrógenos/metabolismoRESUMEN
Dichlorophene (DCP) is a halogenated phenolic compound, widely used as fungicide, bactericide and antiprotozoan and also exhibit therapeutic application in several pathological conditions. Taking account of broad use of DCP, its possible effect on spleen (an important immune organ) was investigated in this study. Male albino rats were treated with graded doses of DCP (10%, 20% and 30% of LD50) and spleen and blood were obtained at 24, 48 and 72 hours post treatment. Oxidative stress parameters, proinflammatory cytokines and protein expression of aryl hydrocarbon receptor (AhR), indoleamine-2, 3-Dioxygenase 1 (IDO1) and nuclear factor erythroid 2-related factor 2 (Nrf2) were measured along with histopathological evaluation of spleen. In the present study, DCP perturbs redox status of splenocytes of rats as evidenced by excess ROS generation, lipid peroxidation and nitric oxide production simultaneously with reduction of antioxidant level [glutathione (GSH)] and inhibition of antioxidative enzymes [superoxide dismutase (SOD) and catalase (CAT)]. Two important proinflammatory cytokines, IL-6 and TNF-α were found to be elevated upon DCP treatment. Moreover, DCP also caused activation of AhR and IDO1 with simultaneous down regulation of Nrf2. All these effects of DCP were found to be dose and duration dependent. DCP also affects the spleen micro-architecture in the present study and these alterations were more prominent in high dose group at 72 hours post treatment. Taken together, all these results suggested that DCP induces oxidative stress and also increases proinflammatory cytokine levels to mount its toxic effect on spleen.
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Dioxigenasas , Receptores de Hidrocarburo de Aril , Animales , Masculino , Antioxidantes/metabolismo , Antioxidantes/farmacología , Citocinas/metabolismo , Dioxigenasas/metabolismo , Dioxigenasas/farmacología , Glutatión/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo , Receptores de Hidrocarburo de Aril/metabolismo , RatasRESUMEN
Purpose. The prevalence and severity of respiratory disorders are very high among coal miners as continuous exposure of workers in such an environment leads to accumulation of dust in the lungs. This study was designed to assess the prevalence of lung function impairment and to determine whether there is any correlation between dust exposure duration and lung function indices. Materials. Two hundred and thirty underground coal dust-exposed workers and 130 age-matched non-exposed workers were recruited from an underground mine in West Bengal, India. A spirometry test was performed for lung function and also basic information on personnel's dust exposure, smoking and respiratory morbidity was collected. Student's t test, Pearson's correlation coefficient (r), uncorrected Pearson's χ2 test and Fischer's exact test were performed for statistical analysis. Results. Lung function indices were significantly (p < 0.050) impaired between the exposed (43.91%) and non-exposed (23.85%) groups. In addition, highly significant decrements in the pulmonary volumes of exposed subjects were also noted. Furthermore, a high negative correlation was observed between spirometric results and exposure time in the exposed group compared with the non-exposed group. Conclusion. This study suggested a positive relationship between exposure time and lung function deterioration.
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Minas de Carbón , Mineros , Exposición Profesional , Carbón Mineral , Polvo/análisis , Humanos , Exposición Profesional/efectos adversosRESUMEN
Background In the present era, obesity is increasing rapidly, and high dietary intake of lipid could be a noteworthy risk factor for the occasion of obesity, as well as nonalcoholic fatty liver disease, which is the independent risk factor for type 2 diabetes and cardiovascular disease. For a long time, high-lipid diet (HLD) in "fast food" is turning into part of our everyday life. So, we were interested in fulfilling the paucity of studies by means of preliminary evaluation of these three alternative doses of HLD on a rat model and elucidating the possible mechanism of these effects and divulging the most alarming dose. Methods Thirty-two rats were taken, and of these, 24 were fed with HLD in three distinctive compositions of edible coconut oil and vanaspati ghee in a ratio of 2:3, 3:2 and 1:1 (n = 8), orally through gavage at a dose of 10 mL/kg body weight for a period of 28 days, whereas the other eight were selected to comprise the control group. Results After completion of the experiment, followed by analysis of data it was revealed that hyperlipidemia with increased liver and cardiac marker enzymes, are associated with hepatocellular injury and cardiac damage. The data also supported increased proinflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α). As oxidative stress parameter increased in both liver and heart, there is also an increased in TNF-α due to an increased expression of inducible nitric oxide (NO) synthase, which led to a high production of NO. Moreover, HLD treatment explicitly weakens reasonability of hepatocytes and cardiomyocytes conceivably through G0/G1 or S stage capture or perhaps by means of enlistment of sub-G0/G1 DNA fragmentation and a sign of apoptosis. Conclusions Based on the outcomes, it tends to be inferred that consequences of the present examination uncovered HLD in combination of 2:3 applies most encouraging systemic damage by reactive oxygen species generation and hyperlipidemia and necroapoptosis of the liver and heart. Hence, outcome of this study may help to formulate health care strategy and warns about the food habit in universal population regarding the use of hydrogenated and saturated fats (vanaspati ghee) in diet.
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Antioxidantes/metabolismo , Dieta Alta en Grasa/efectos adversos , Radicales Libres/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Animales , Apoptosis/efectos de los fármacos , Hígado/metabolismo , Masculino , Miocardio/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/biosíntesis , Estrés Oxidativo , RatasRESUMEN
Context: Alteration of redox signalling and RANK-L expression in FBMCs of mice exposed to different intensities of cold stress (15 °C, 8 °C and 4 °C) were studied.Objective: To understand the effects of varying intensities of cold stress on murine FBMCs and its impact on osteoclastogenesis.Materials and methods: FBMCs were isolated from mice exposed to different intensities of cold stress and used for immunoblotting and biochemical assays. Bone histometry was also done.Results: Different intensities of cold stress perturb redox signalling in FBMCs and alters bone histometry. Higher RANK-L expressions were noted in FBMCs of mice exposed to 8 °C and 4 °C as compared with 15 °C.Discussion and conclusion: Cold stress boosts free radical production in FBMC's, which might enhance RANK-L expression, an indicator of osteoclastogenesis. Thus, we speculate that stronger cold stress (8 °C and 4 °C) contributes to the development of early bone loss.
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Células de la Médula Ósea/citología , Respuesta al Choque por Frío , Osteoclastos/citología , Transducción de Señal , Animales , Femenino , Ratones , Óxido Nítrico/biosíntesis , Osteoclastos/metabolismo , Oxidación-ReducciónRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Tinospora sinensis Lour. (Merr.) belongs to the family Menispermaceae and its stem extract have been used traditionally in broad aspects of therapeutic remedies including debility, dyspepsia, fever, jaundice, ulcer, bronchitis, urinary disease, skin disease, liver disease and diabetes. AIM OF THE STUDY: The aim of the study was to evaluate the protective effects of methanol extract of stem of Tinospora sinensis (METS) on streptozotocin induced pancreatic islet cell injuries of diabetic rats and its correlation to its phytochemical profiles. MATERIALS AND METHODS: A high-performance liquid chromatography technique (HPLC) was used to identify and quantify the major phytochemicals present in the METS. Diabetic rats were administered with METS at a dose of (100, 200 and 400â¯mg/kg respectively orally) and standard drug Metformin (300â¯mg/kg) was given orally to group serving positive control. Effect of the METS on glucose homeostasis, oxidative stress, antioxidant status, histopathology of pancreas and also on intracellular reactive oxygen species (ROS), mitochondrial membrane potential, apoptosis, cell cycle of pancreatic islet cells were studied in diabetic rats. RESULTS: The major phytochemicals identified and quantified by HPLC in the extract were berberine, caffeic acid, myricetin and ferulic acid. This result showed that methanol extract exhibited good antioxidant effect. The methanol extract of the plant prevented the diabetogenic effect of STZ and significantly lowered the fasting blood glucose level, glycated haemoglobin and increased insulin and C-peptide level in treated rats. METS reduced apoptosis of STZ treated islet cells by significantly decreasing pro-inflammatory cytokines (TNFα, IL6), intracellular ROS generation, lipid peroxidation, nitric oxide (NO) production and increasing mitochondrial membrane potential and sub-G0 peak area, enzymatic and nonenzymatic antioxidants. CONCLUSION: The results revealed that the methanol extract of the stem of the plant possesses protective effects against diabetes and associated complications.
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Antiinflamatorios/farmacología , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Diabetes Mellitus Experimental/prevención & control , Hipoglucemiantes/farmacología , Islotes Pancreáticos/efectos de los fármacos , Extractos Vegetales/farmacología , Tinospora , Animales , Antiinflamatorios/aislamiento & purificación , Antioxidantes/aislamiento & purificación , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Hemoglobina Glucada/metabolismo , Hipoglucemiantes/aislamiento & purificación , Mediadores de Inflamación/metabolismo , Islotes Pancreáticos/metabolismo , Islotes Pancreáticos/patología , Peroxidación de Lípido/efectos de los fármacos , Lípidos/sangre , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/patología , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/aislamiento & purificación , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Estreptozocina , Tinospora/químicaRESUMEN
Evaluation of the modulatory effect of ethanolic extract of Alocasia indica tuber (EEAIT) against γ-irradiation induced ovarian and uterine toxicity. Extract preparation was done by 80% hydro-ethanol using Soxhlet apparatus. EEAIT was administered to female Swiss albino mice (n = 5) daily (200 and 400 mg/kg body weight/d) for 7 days before γ-irradiation exposure (2.9 Gy). FSH, LH, estrogen, progesterone, cytokine levels, and oxidative stress parameters were measured after 24 hours of γ-irradiation. Histology, folliculogenesis, viability of granulosa cells, ROS measurement by flow cytometry, western blot of P450scc, P45017A1, 3ß HSD and SF 1 were also performed. In addition, fertility status was assessed by fecundability and fecundity. The results showed that EEAIT exhibit a strong radioprotective activity by reducing the oxidative stress and thereby restored the ovarian and uterine alterations. EEAIT also improved the abnormality in follicle development, restored altered gonadal hormones and cytokines levels, increase the fertility status, reducing ROS level of granulosa cells with increasing granulosa cells viability and steroidogenic enzyme activity as compared to control. So EEAIT showed a radioprotective effect on γ-irradiation induced ovarian and uterine damage. Our results suggested that Alocasia indica tuber can be a potential radioprotector to prevent female infertility.
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Alocasia/química , Ovario/efectos de los fármacos , Extractos Vegetales/farmacología , Traumatismos por Radiación/prevención & control , Protectores contra Radiación/farmacología , Útero/efectos de los fármacos , Animales , Antioxidantes/metabolismo , Catalasa/metabolismo , Supervivencia Celular/efectos de la radiación , Citocinas/metabolismo , Etanol/química , Femenino , Fertilidad/efectos de la radiación , Rayos gamma , Células de la Granulosa/efectos de la radiación , Malondialdehído/metabolismo , Ratones , Óxido Nítrico/metabolismo , Ovario/efectos de la radiación , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismo , Útero/efectos de la radiaciónRESUMEN
Accelerating prevalence of coal workers pneumoconiosis is considered as a serious occupational health problem. This cross-sectional study was designed to determine the prevalence of lung function impairment of underground coal miners in West Bengal, India. A total of 230 underground coal dust-exposed subjects and 130 nonexposed subjects were examined for lung function test and also information on sociodemographic characteristics, addiction, respiratory morbidity, personnel protective equipment and dust exposure were collected. Lung function impairment was significantly higher in exposed group than nonexposed group and personnel dust exposure level were exceeded above the NIOSH recommended level. In addition, respiratory ailments were found to be higher in exposed group than the nonexposed group. So, this study has established the need for an advanced understanding of the quantifiable and measurable remedies for protection of lung disorder of coal mine workers.
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Carbón Mineral , Polvo/análisis , Mineros , Enfermedades Profesionales/epidemiología , Exposición Profesional , Insuficiencia Respiratoria/epidemiología , Insuficiencia Respiratoria/etiología , Fumar/efectos adversos , Adulto , Estudios Transversales , Encuestas Epidemiológicas , Humanos , India/epidemiología , Enfermedades Pulmonares , Persona de Mediana Edad , Exposición Profesional/efectos adversos , Prevalencia , Fumar/epidemiologíaRESUMEN
Exposure to bisphenol A (BPA), an endocrine disruptor and environmental toxicant, is associated with adverse estrogenic effects in both humans and wildlife species. Because the effects of BPA on the ovary at the cellular level are incompletely understood, the present study was designed to investigate the underlying mechanism of granulosa cell injury following BPA exposure. Eight-week-old female Wistar rats were treated with BPA (25 mg/kg BW/day for 9 days, intraperitonially) with or without pretreatment of the catalase-specific blocker 3-amino-1,2,4-triazole (ATZ; 1 g/kg BW/day for 5 days, intraperitonially). Different oxidative and antioxidant stress parameters, pro-inflammatory cytokines, and hormonal levels were measured. Catalase expression in isolated granulosa cells was analyzed by Western blot. There were noticeable increases in both nitric oxide and lipid peroxidation levels in the granulosa cells of the BPA-treated group with or without pretreatment with ATZ. Compared with the controls, BPA exposure resulted in a significant increase in pro-inflammatory cytokine levels that was further increased following pretreatment with ATZ. Results of the hormonal assays clearly showed a significant decrease in both estrogen and progesterone levels. In contrast, there was a significant increase in both serum follicle-stimulating hormone and luteinizing hormone levels following BPA exposure, with or without ATZ pretreatment. Results of Western blot analysis demonstrated decreased expression of catalase in the BPA-treated group and a further decrease in expression in the group treated with both BPA and ATZ. Our data suggest that catalase plays a role in mediating reproductive damage to granulosa cells exposed to BPA.
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Amitrol (Herbicida)/farmacología , Compuestos de Bencidrilo/toxicidad , Catalasa/antagonistas & inhibidores , Células de la Granulosa/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Fenoles/toxicidad , Animales , Catalasa/efectos de los fármacos , Citocinas/análisis , Citocinas/metabolismo , Femenino , RatasRESUMEN
Nicotine, one of the well-known highly toxic components of cigarette smoke, causes a number of adverse health effects and diseases. Our previous study has shown that nicotine induces reactive oxygen species (ROS) in islet cell and disrupts islet cell mitochondrial membrane potential (ΔΨm). However, supplementation with folic acid and vitamin B12 were found effective against nicotine induced changes in pancreatic islet cells. But the toxicological effects and underlying mechanisms of nicotine-induced mitochondrial dysfunction is still unknown. In this study, nicotine exposure decreases mitochondrial enzymes (pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, aconitase, malate dehydrogenase) activities by increasing cytosolic Ca2+ level which may contribute to increased mitochondrial ROS production by raising its flow to mitochondria. This in turn produces malondialdehyde and nitric oxide (NO) with a concomitant decrease in the activities of antioxidative enzymes and glutathione levels leading to loss of ΔΨm. Simultaneously, nicotine induces pancreatic islet cell apoptosis by modulating ΔΨm via increased cytosolic Ca2+ level, altered Bcl-2, Bax, cytochrome c, caspase-9, PARP expressions which were prevented by the supplementation of folic acid and vitamin B12 . In conclusion, nicotine alters islet cell mitochondrial redox status, apoptotic machinery, and enzymes to cause disruption in the ΔΨm and supplementation of folic acid and vitamin B12 possibly blunted all these mitochondrial alterations. Therefore, this study may help to determine the pathophysiology of nicotine-mediated islet cell mitochondrial dysfunction.