Barriers and facilitators to informal healthcare provider engagement in the national tuberculosis elimination program of India: An exploratory study from West Bengal.

India has a high burden of Tuberculosis (TB), accounting for a significant portion of global cases. While efforts are being made to engage the formal private sector in the National TB Elimination Program (NTEP) of India, there remains a significant gap in addressing the engagement of Informal Healthcare Providers (IPs), who serve as the first point of contact for healthcare in many communities. Recognizing the increasing evidence of IPs' importance in TB care, it is crucial to enhance their engagement in the NTEP. Therefore, this study explored various factors influencing the engagement of IPs in the program. A qualitative study was conducted in West Bengal, India, involving 23 IPs and 11 Formal Providers (FPs) from different levels of the formal health system. Thematic analysis of the data was conducted following a six-step approach outlined by Braun and Clarke. Three overarching themes were identified in the analysis, encompassing barriers and facilitators to IPs' engagement in the NTEP. The first theme focused on IPs' position and capacity as care providers, highlighting their role as primary care providers and the trust and acceptance extended by the community. The second theme explored policy and system-level drivers and prohibitors, revealing barriers such as role ambiguity, competing tasks, and quality of care issues. Facilitators such as growing recognition of IPs' importance in the health system, an inclusive incentive system, and willingness to collaborate were also identified. The third theme focused on the relationship between the formal and informal systems, highlighting a need to strengthen the relationship between the two. This study sheds light on factors influencing the engagement of IPs in the NTEP of India. It emphasizes the need for role clarity, knowledge enhancement, and improved relationships between formal and informal systems. By addressing these factors, policymakers and stakeholders can strengthen the engagement of IPs in the NTEP.

Stepwise evaluation for the risk of metabolic unhealthiness and significant non-alcoholic fatty liver disease in India.

Background: Non-communicable diseases including metabolic health disorders are becoming area of concern for low/middle income countries with poor health-care resources. Present study was planned to assess the prevalence of metabolically unhealthy (MU) subjects in the community and proportion of the MU subjects having the risk of significant Non-alcoholic Fatty Liver Disease (NAFLD) using a step-wise evaluation strategy in a resource-poor setting. Methods: Study was performed in 19 community development blocks of Birbhum district, West Bengal, India. Every fifth member in the electoral list was included for the first step evaluation (n = 79,957/1,019,365, 7.8%) to detect any metabolic risk. Subjects with any metabolic risk in the first step (n = 9819/41,095, 24%) were taken for second step evaluation with Fasting blood glucose (FBG) and ALT. Subjects with elevated FBG and/or ALT in the second step (n = 1403/5283, 27%) were taken into third step evaluation. Finding: At least one risk factor was found in 51.4% (n = 41,095/79,957). 63% (n = 885/1403) of the subjects with metabolic abnormality (third step) had MU state making its overall prevalence of 1.1% (n = 885/79,957). 53% of MU subjects (n = 470/885) had 'persistently elevated ALT' suggesting the risk of having significant NAFLD. Interpretation: Step-wise evaluation strategy could detect the subjects at risk, actually having MU state and proportion of MU subjects at risk of having 'persistently elevated ALT' (surrogate of significant NAFLD) in the community with minimum utilization of scarce resources. Funding: This study was funded by Bristol Myers Squibb Foundation, USA, under the program 'Together on Diabetes Asia' (Project Number: 1205 - LFWB).

Are informal healthcare providers knowledgeable in tuberculosis care? A cross-sectional survey using vignettes in West Bengal, India.

BACKGROUND: India accounts for one-quarter of the world's TB cases. Despite efforts to engage the private sector in India's National TB Elimination Program, informal healthcare providers (IPs), who serve as the first contact for a significant TB patients, remain grossly underutilised. However, considering the substantial evidence establishing IPs' role in patients' care pathway, it is essential to expand the evidence base regarding their knowledge in TB care. METHODS: We conducted a cross-sectional study in the Birbhum district of West Bengal, India. The data were collected using the TB vignette among 331 IPs (165 trained and 166 untrained). The correct case management was defined following India's Technical and Operational Guidelines for TB Control. RESULTS: Overall, IPs demonstrated a suboptimal level of knowledge in TB care. IPs exhibited the lowest knowledge in asking essential history questions (all four: 5.4% and at least two: 21.7%) compared with ordering sputum test (76.1%), making a correct diagnosis (83.3%) and appropriate referrals (100%). Nonetheless, a statistically significant difference in knowledge (in most domains of TB care) was observed between trained and untrained IPs. CONCLUSIONS: This study identifies gaps in IPs' knowledge in TB care. However, the observed significant difference between the trained and untrained groups indicates a positive impact of training in improving IPs' knowledge in TB care.

What are the tuberculosis care practices of informal healthcare providers? A cross-sectional study from Eastern India.

India is the highest TB burden country, accounting for an estimated 26% of the global TB cases. Systematic engagement of the private sector is a cornerstone of India's National Strategic Plan for TB Elimination (2017-25). However, informal healthcare providers (IPs), who are the first point of contact for a large number of TB patients, remain significantly underutilized in the National TB Elimination Program of India. Non-prioritization of IPs has also resulted in a limited understanding of their TB care practices in the community. We, therefore, undertook a descriptive study to document IPs' TB care practices, primarily focusing on their approach to screening, diagnosis, treatment and referral. This cross-sectional study was carried out from February to March 2020 in the Birbhum District of West Bengal, India. Interviews were conducted utilizing the retrospective case study method. A total of 203 IPs participated who reported seeing at least one confirmed TB patient in 6 months prior to the study. In that duration, IPs reported interacting with an average of five suspected TB cases, two of which were later confirmed as having TB. Antibiotic use was found to be common among IPs (highest 69% during the first visit); however, they were prescribed before the patient was suspected or confirmed as having TB. We noted the practice of prolonged treatment among IPs as patients were prescribed medicines until the second follow-up visit. Referral was the preferred TB case management approach among IPs, but delayed referral was observed, with only one-third (34%) of patients being referred to higher health facilities during their first visit. This study presents important findings on IPs' TB care practices, which have consequences for achieving India's national goal of TB elimination.

Predictors of COVID-19 Vaccine Confidence: Findings from Slums of Four Major Metro Cities of India.

There are limited studies on COVID vaccine confidence at the household level in urban slums, which are at high risk of COVID-19 transmission due to overcrowding and poor living conditions. The objective was to understand the reasons influencing COVID-19 vaccine confidence, in terms of barriers and enablers faced by communities in urban slums and informal settlements in four major metro cities in India. A mixed method approach was adopted, where in field studies were conducted during April-May 2021. First, a survey of at least 50 subjects was conducted among residents of informal urban settlements who had not taken any dose of the COVID-19 vaccine in Mumbai, Bengaluru, Kolkata and Delhi; second, a short interview with five subjects who had taken at least one dose of the vaccine in each of the four cities to understand the factors that contributed to positive behaviour and, finally, an in-depth interview of at least 3 key informants in each city to ascertain the vaccination pattern in the communities. The reasons were grouped under contextual, individual/group and vaccine/vaccination specific issues. The most frequent reason (27.7%) was the uncertainty of getting the vaccine. The findings show the need for increasing effectiveness of awareness campaigns, accessibility and the convenience of vaccination, especially among vulnerable groups, to increase the uptake.

Multi-walled carbon nanotubes inhibit estrogen receptor expression in vivo and in vitro through transforming growth factor beta1.

Exposure to multi-walled carbon nanotubes (MWCNTs) is suspected to contribute to pulmonary fibrosis through modulation of transforming growth factor beta1 (TGF-ß1). There is growing evidence that estrogen signaling is important in pulmonary function and modulates pro-fibrogenic signaling in multiple models of pulmonary fibrosis, however an interaction between MWCNT exposure and estrogen signaling in the lung is not known. The purpose of this work was to determine whether estrogen signaling in the lung is a target for MWCNTs and to identify potential signaling mechanisms mediating MWCNT-induced responses using a whole-body inhalation mouse model and an in vitro human lung cell model. Mice exposed to MWCNTs had reduced mRNA expression of estrogen receptor alpha and beta (Esr1 and Esr2, respectively) in lung tissue at multiple time-points post-exposure, whereas expression of g-protein coupled estrogen receptor1 (Gper1) was more variable. We localized ESR1 protein expression as primarily associated with bronchioles and within inflammatory macrophages. The reduction in estrogen receptor expression was concomitant to an increase in TGF-ß1 levels in the bronchoalveolar lavage fluid (BALF) of MWCNT-exposed animals. We confirmed a role for TGF-ß1 in mediating MWCNT-induced repression of ESR1 mRNA expression using a TGF-ß type-I receptor inhibitor in bronchial epithelial cells in vitro. Overall these results highlight a novel mechanism of MWCNT-induced signaling where MWCNT-induced regulation of TGF-ß1 represses estrogen receptor expression. Dysregulated estrogen signaling through altered receptor expression may have potential consequences on lung function.

Aggregation Behavior of Multiwalled Carbon Nanotube-Titanium Dioxide Nanohybrids: Probing the Part-Whole Question.

Multiwalled carbon nanotube-titanium dioxide (MWNT-TiO2) nanohybrids (NHs), a promising support for electrocatalysts, have a high likelihood of environmental release. Aggregation of these NHs may or may not be captured by the sum of their component behavior, thus necessitating a systematic evaluation. This study probes the "part-whole question" by systematically evaluating the role of TiO2 loading (C:Ti molar ratios of 1:0.1, 1:0.05 and 1:0.033) on the aggregation behavior of these NHs. Aggregation kinetics of these in-house synthesized (using a sol-gel method) NHs and the components is investigated with time-resolved dynamic light scattering in the presence of mono- and divalent cations and with and without Suwannee River humic acid. A deviation in the aggregation behavior from classical electrokinetic theory has been observed which indicates that the material complexity has a strong influence in the observed behavior; hence other material attributes (e.g., fractal dimension, surface roughness, charge heterogeneity, etc.) should be carefully considered when studying such materials. The sum of the aggregation behavior of the parts may not capture that of the whole (i.e., of the NHs); aggregation depends on the TiO2 loading and also on the hybridization process and the background aquatic chemistry.

Insights into Metal Oxide and Zero-Valent Metal Nanocrystal Formation on Multiwalled Carbon Nanotube Surfaces during Sol-Gel Process.

Carbon nanotubes are hybridized with metal crystals to impart multifunctionality into the nanohybrids (NHs). Simple but effective synthesis techniques are desired to form both zero-valent and oxides of different metal species on carbon nanotube surfaces. Sol-gel technique brings in significant advantages and is a viable technique for such synthesis. This study probes the efficacy of sol-gel process and aims to identify underlying mechanisms of crystal formation. Standard electron potential (SEP) is used as a guiding parameter to choose the metal species; i.e., highly negative SEP (e.g., Zn) with oxide crystal tendency, highly positive SEP (e.g., Ag) with zero-valent crystal-tendency, and intermediate range SEP (e.g., Cu) to probe the oxidation tendency in crystal formation are chosen. Transmission electron microscopy and X-ray diffraction are used to evaluate the synthesized NHs. Results indicate that SEP can be a reliable guide for the resulting crystalline phase of a certain metal species, particularly when the magnitude of this parameter is relatively high. However, for intermediate range SEP-metals, mix phase crystals can be expected. For example, Cu will form Cu2O and zero-valent Cu crystals, unless the synthesis is performed in a reducing environment.

Single-walled carbon nanotubes modulate pulmonary immune responses and increase pandemic influenza a virus titers in mice.

BACKGROUND: Numerous toxicological studies have focused on injury caused by exposure to single types of nanoparticles, but few have investigated how such exposures impact a host's immune response to pathogen challenge. Few studies have shown that nanoparticles can alter a host's response to pathogens (chiefly bacteria) but there is even less knowledge of the impact of such particles on viral infections. In this study, we performed experiments to investigate if exposure of mice to single-walled carbon nanotubes (SWCNT) alters immune mechanisms and viral titers following subsequent influenza A virus (IAV) infection. METHODS: Male C57BL/6 mice were exposed to 20 µg of SWCNT or control vehicle by intratracheal instillation followed by intranasal exposure to 3.2 × 104 TCID50 IAV or PBS after 3 days. On day 7 mice were euthanized and near-infrared fluorescence (NIRF) imaging was used to track SWCNT in lung tissues. Viral titers, histopathology, and mRNA expression of antiviral and inflammatory genes were measured in lung tissue. Differential cell counts and cytokine levels were quantified in bronchoalveolar lavage fluid (BALF). RESULTS: Viral titers showed a 63-fold increase in IAV in SWCNT + IAV exposed lungs compared to the IAV only exposure. Quantitation of immune cells in BALF indicated an increase of neutrophils in the IAV group and a mixed profile of lymphocytes and neutrophils in SWCNT + IAV treated mice. NIRF indicated SWCNT remained in the lung throughout the experiment and localized in the junctions of terminal bronchioles, alveolar ducts, and surrounding alveoli. The dual exposure exacerbated pulmonary inflammation and tissue lesions compared to SWCNT or IAV single exposures. IAV exposure increased several cytokine and chemokine levels in BALF, but greater levels of IL-4, IL-12 (P70), IP-10, MIP-1, MIP-1α, MIP-1ß, and RANTES were evident in the SWCNT + IAV group. The expression of tlr3, ifnß1, rantes, ifit2, ifit3, and il8 was induced by IAV alone but several anti-viral targets showed a repressed trend (ifits) with pre-exposure to SWCNT. CONCLUSIONS: These findings reveal a pronounced effect of SWCNT on IAV infection in vivo as evidenced by exacerbated lung injury, increased viral titers and several cytokines/chemokines levels, and reduction of anti-viral gene expression. These results imply that SWCNT can increase susceptibility to respiratory viral infections as a novel mechanism of toxicity.

Influence of the Gastrointestinal Environment on the Bioavailability of Ethinyl Estradiol Sorbed to Single-Walled Carbon Nanotubes.

Recent evidence suggests that, because of their sorptive nature, if single-walled carbon nanotubes (SWCNTs) make their way into aquatic environments, they may reduce the toxicity of other waterborne contaminants. However, few studies have examined whether contaminants remain adsorbed following ingestion by aquatic organisms. The objective of this study was to examine the bioavailability and bioactivity of ethinyl estradiol (EE2) sorbed onto SWCNTs in a fish gastrointestinal (GI) tract. Sorption experiments indicated that SWCNTs effectively adsorbed EE2, but the chemical was still able to bind and activate soluble estrogen receptors (ERs) in vitro. However, centrifugation to remove SWCNTs and adsorbed EE2 significantly reduced ER activity compared to that of EE2 alone. Additionally, the presence of SWCNTs did not reduce the extent of EE2-driven induction of vitellogenin 1 in vivo compared to the levels in organisms exposed to EE2 alone. These results suggest that while SWCNTs adsorb EE2 from aqueous solutions, under biological conditions EE2 can desorb and retain bioactivity. Additional results indicate that interactions with gastrointestinal proteins may decrease the level of adsorption of estrogen to SWCNTs by 5%. This study presents valuable data for elucidating how SWCNTs interact with chemicals that are already present in our aquatic environments, which is essential for determining their potential health risk.

Study of arsenic accumulation in rice and evaluation of protective effects of Chorchorus olitorius leaves against arsenic contaminated rice induced toxicities in Wistar albino rats.

BACKGROUND: In the present study, we investigated the arsenic accumulation in different parts of rice irrigated with arsenic contaminated water. Besides, we also evaluated the protective effects of Corchorus olitorius leaves against arsenic contaminated rice induced toxicities in animal model. METHODS: A pot experiment was conducted with arsenic amended irrigation water (0.0, 25.0, 50.0 and 75.0 mg/L As) to investigate the arsenic accumulation in different parts of rice. In order to evaluate the protective effects of Corchorus olitorius leaves, twenty Wistar albino rats were divided into four different groups. The control group (Group-I) was supplied with normal laboratory pellets while groups II, III, and IV received normal laboratory pellets supplemented with arsenic contaminated rice, C. olitorius leaf powder (4 %), arsenic contaminated rice plus C. olitorius leaf powder (4 %) respectively. Different haematological parameters and serum indices were analyzed to evaluate the protective effects of Corchorus olitorius leaves against arsenic intoxication. To gather more supportive evidences of Corchorus olitorius potentiality against arsenic intoxication, histopathological analysis of liver, kidney, spleen and heart tissues was also performed. RESULTS: From the pot experiment, we have found a significant (p ≤ 0.05) increase of arsenic accumulation in different parts of rice with the increase of arsenic concentrations in irrigation water and the trend of accumulation was found as root > straw > husk > grain. Another part of the experiment revealed that supplementation of C. olitorius leaves with arsenic contaminated rice significantly (p < 0.05) restored the altered haematological parameters and other serum indices towards the normal values. Arsenic deposition pattern on different organs and histological studies on the ultrastructural changes of liver, kidneys, spleen and heart also supported the protective roles of Corchorus olitorius leaves against arsenic contaminated rice induced toxicities. CONCLUSION: Arsenic accumulation in different parts of rice increased dose-dependently. Hence, for irrigation purpose arsenic contaminated water cannot be used. Furthermore, arsenic contaminated rice induced several toxicities in animal model, most of which could be minimized with the food supplementation of Corchorus olitorius leaves. Therefore, Corchorus olitorius can be used as a potential food supplement to the affected people of arsenic prone zone to ensure the food security.

Co-transport of gold nanospheres with single-walled carbon nanotubes in saturated porous media.

Porous media transport of engineered nanomaterials (ENMs) is typically assessed in a controlled single-particulate environment. Presence of a secondary particle (either natural or engineered) in the natural environment though likely, is rarely taken into consideration in assessing ENMs' transport behavior. This study systematically assesses the effect of a secondary ENM (i.e., pluronic acid modified single-walled carbon nanotubes, PA-SWNTs) on a primary particle (i.e., gold nanospheres, AuNSs) transport through saturated porous media under a wide range of aquatic conditions (1-100 mM NaCl). AuNS hetero-dispersions (i.e., with PA-SWNTs) are transported through saturated sand columns, and the transport behavior is compared to AuNS-only homo-dispersion cases, which display classical ionic strength-dependent behavior. AuNS hetero-dispersion, however, is highly mobile with little to no ionic strength-dependent effects. This study also assesses the role of pre-coating of the collectors with PA-SWNTs on AuNSs' mobility, thereby elucidating the role played by the order of introduction of the secondary particles. Pre-existence of the secondary particles in the porous media shows enhanced filtration of primary AuNSs. However, the presence of natural organic matter (NOM) slightly increases AuNS mobility through PA-SWNT coated sand at 10 mM ionic strength. The study results demonstrate that the presence and order of addition of the secondary particles strongly influence primary particles' mobility. Thus ENMs can demonstrate facilitated transport or enhanced removal, depending on the presence of the secondary particulate matter and background solution chemistry.

Aggregation Kinetics of Higher-Order Fullerene Clusters in Aquatic Systems.

The aggregation kinetics of nC60 and higher-order fullerene (HOF) clusters, i.e., nC70, nC76, and nC84, was systematically studied under a wide range of mono- (NaCl) and divalent (CaCl2) electrolytes and using time-resolved dynamic light scattering. Suwanee River Humic Acid (SRHA) was also used to determine the effect of natural macromolecules on nHOF aggregation. An increase in electrolyte concentration resulted in electrical double-layer compression of the negatively charged fullerene clusters, and the nC60s and nHOFs alike displayed classical Derjaguin-Landau-Verwey-Overbeek (DLVO) type interaction. The critical coagulation concentration (CCC) displayed a strong negative correlation with the carbon number in fullerenes and was estimated as 220, 150, 100, and 70 mM NaCl and 10, 12, 6, and 7.5 mM CaCl2 for nC60, nC70, nC76, and nC84, respectively. The aggregation mechanism (i.e., van der Waals interaction domination) was enumerated via molecular dynamics simulation and modified DLVO model. The presence of SRHA (2.5 mg TOC/L) profoundly influenced the aggregation behavior by stabilizing all fullerene clusters, even at a 100 mM NaCl concentration. The results from this study can be utilized to predict aggregation kinetics of nHOF clusters other than the ones studied here. The scaling factor for van der Waals interaction can also be used to model nHOF cluster interaction.

Gold-conjugated green tea nanoparticles for enhanced anti-tumor activities and hepatoprotection--synthesis, characterization and in vitro evaluation.

Green tea (GT)-based chemoprevention has shown promising results in various cancer models. However, the effective dose may not be far from the toxic dose because of inefficient systemic delivery and limited bio-availability of GT polyphenols. We have used GT polyphenols to successfully reduce gold to corresponding gold nanoparticles (NPs) in a single step; a process that fulfils all criteria of green nanotechnology as no "man-made" chemical other than gold acids are used. GT and (-) - epigallocatechin-3-gallate (EGCG) conjugated gold NPs (diameters <50 nm), showed remarkable stability, significantly rapid cellular uptake and excellent in vitro anti-oxidant activities. These NPs were observed to be selectively toxic towards cancer cells (Ehrlich's Ascites Carcinoma and MCF-7) while showing absolutely no lethality towards normal primary mouse hepatocytes. In cancer cells, NPs altered the redox status and limited Nrf2 activation by almost 50%. These NPs significantly decreased nuclear translocation of NF-κB, coupled with decreased phosphorylation of IĸB and down-regulation of NF-κB-dependent anti-apoptotic proteins Bcl2 and Akt in a dose-dependent manner, triggering onset of apoptosis. Culturing normal hepatocytes with tumor-conditioned media prompted apoptosis by increasing reactive oxygen species (ROS) and depleting the anti-oxidant defense mechanism of hepatocytes. Pre-treatment with NPs protected hepatocytes from tumor-induced cellular damage by scavenging excess ROS, increasing the levels of reduced glutathione and anti-oxidant enzymes. There was evidence of decreased Bax/Bcl2 ratio and active Caspase 3 levels in these hepatocytes, indicating apoptosis escape. Nanoformulations of GT-based polyphenols might serve as an operative platform for effective delivery, increased bio-availability, enhanced effects and minimal chemotherapy-associated toxicities.

Gossypetin ameliorates ionizing radiation-induced oxidative stress in mice liver--a molecular approach.

Radioprotective action of gossypetin (GTIN) against gamma (γ)-radiation-induced oxidative stress in liver was explored in the present article. Our main aim was to evaluate the protective efficacy of GTIN against radiation-induced alteration of liver in murine system. To evaluate the effect of GTIN, it was orally administered to mice at a dose of 30 mg/kg body weight for three consecutive days prior to γ-radiation at a dose of 5 Gy. Radioprotective efficacy of GTIN were evaluated at physiological, cellular, and molecular level using biochemical analysis, comet assay, flow cytometry, histopathology, immunofluorescence, and immunoblotting techniques. Ionizing radiation was responsible for augmentation of hepatic oxidative stress in terms of lipid peroxidation and depletion of endogenous antioxidant enzymes. Immunoblotting and immunofluorescence studies showed that irradiation enhanced the nuclear translocation of nuclear factor kappa B (NF-κB) level, which leads to hepatic inflammation. To investigate further, we found that radiation induced the activation of stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK)-mediated apoptotic pathway and deactivation of the NF-E2-related factor 2 (Nrf2)-mediated redox signaling pathway, whereas GTIN pretreatment ameliorated these radiation-mediated effects. This is the novel report where GTIN rationally validated the molecular mechanism in terms of the modulation of cellular signaling system' instead of ' This is the novel report where GTIN is rationally validated in molecular terms to establish it as promising radioprotective agents. This might be fruitful especially for nuclear workers and defense personnel assuming the possibility of radiation exposure.

Seabuckthron (Hippophae rhamnoides L.) leaf extract ameliorates the gamma radiation mediated DNA damage and hepatic alterations.

In vitro assessment showed that H. rhamnoides (HrLE) extract possessed free radical scavenging activities and can protect gamma (gamma) radiation induced supercoiled DNA damage. For in vivo study, Swiss albino mice were administered with HrLE (30 mg/kg body weight) for 15 consecutive days before exposing them to a single dose of 5 Gy of beta radiation. HrLE significantly prevented the radiation induced genomic DNA damage indicated as a significant reduction in the comet parameters. The lipid peroxidation, liver function enzymes, expression of phosphorylated NFkappaB (p65) and IkappaBalpha increased whereas the endogenous antioxidants diminished upon radiation exposure compared to control. Pretreatment of HrLE extract ameliorated these changes. Based on the present results it can be concluded that H. rhamnoides possess a potential preventive element in planned and accidental nuclear exposures.

Protective effect of coconut water concentrate and its active component shikimic acid against hydroperoxide mediated oxidative stress through suppression of NF-κB and activation of Nrf2 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Conventionally coconut water has been used as an 'excellent hydrating' drink that maintain the electrolyte balance and help in treating diverse ailments related to oxidative stress including liver function. The present study was aimed to elucidate whether and how the coconut water concentrate (CWC) and its major active phytoconstituent shikimic acid (SA) can effectively protect murine hepatocytes from the deleterious effect of hydroperoxide-mediated oxidative stress. MATERIALS AND METHODS: Bioactivity guided fractionation of CWC resulted in the isolation of a couple of known compounds. Freshly isolated murine hepatocytes were exposed to hydrogen peroxide (H2O2) (1 and 3mM) in the presence or absence of CWC (200 and 400 µg/ml) and SA (40 µM) for the determination of antioxidative, DNA protective, cellular ROS level by modern methods, including immunoblot and flowcytometry to find out the possible mechanism of action. RESULTS: Pre-treatment of hepatocyte with CWC and SA showed significant prevention of H2O2-induced intracellular ROS generation, nuclear DNA damage along with the formation of hepatic TBARS and cellular nitrite. Further, the H2O2 induced cell death was arrested in the presence of CWC through the inhibition of CDC42 mediated SAPK/JNK pathways and activation of other molecules of apoptotic pathways, including Bax and caspase3. Moreover, CWC and SA help in maintaining the GSH level and endogenous antioxidants like Mn-SOD, to support intracellular defense mechanisms, probably through the transcriptional activation of Nrf2; and inhibition of nuclear translocation of NF-κB. CONCLUSION: CWC and its active components SA reversed the H2O2 induced oxidative damage in hepatocytes, probably through the inhibition of NF-κB, with the activation of PI3K/Akt/Nrf2 pathway and reduction of apoptosis by interfering the SAPK/JNK/Bax pathway.

Role of ferulic acid in the amelioration of ionizing radiation induced inflammation: a murine model.

Ionizing radiation is responsible for oxidative stress by generating reactive oxygen species (ROS), which alters the cellular redox potential. This change activates several redox sensitive enzymes which are crucial in activating signaling pathways at molecular level and can lead to oxidative stress induced inflammation. Therefore, the present study was intended to assess the anti-inflammatory role of ferulic acid (FA), a plant flavonoid, against radiation-induced oxidative stress with a novel mechanistic viewpoint. FA was administered (50 mg/kg body wt) to Swiss albino mice for five consecutive days prior to exposing them to a single dose of 10 Gy 60Co γ-irradiation. The dose of FA was optimized from the survival experiment and 50 mg/kg body wt dose showed optimum effect. FA significantly ameliorated the radiation induced inflammatory response such as phosphorylation of IKKα/ß and IκBα and consequent nuclear translocation of nuclear factor kappa B (NF-κB). FA also prevented the increase of cycloxygenase-2 (Cox-2) protein, inducible nitric oxide synthase-2 (iNOS-2) gene expression, lipid peroxidation in liver and the increase of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in serum. It was observed that exposure to radiation results in decreased activity of superoxide dismutase (SOD), catalase (CAT) and the pool of reduced glutathione (GSH) content. However, FA treatment prior to irradiation increased the activities of the same endogenous antioxidants. Thus, pretreatment with FA offers protection against gamma radiation induced inflammation.

Gossypetin, a naturally occurring hexahydroxy flavone, ameliorates gamma radiation-mediated DNA damage.

PURPOSE: To evaluate the protective effect of gossypetin (GTIN) against gamma (γ)-radiation-mediated DNA damage. MATERIALS AND METHODS: Increasing concentrations (10-150 µM) of GTIN were incubated with supercoiled DNA 1 h prior exposure to γ-radiation in the range of 5-Gy absorbed dose from Co(60) γ source. To establish the effective protective concentration of GTIN, supercoiled DNA was pre-incubated with 50 µM of GTIN for 1 h followed by exposure of 5, 10 and 20 Gy doses of γ-radiation. Moreover, 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical, hydroxyl radical, nitric oxide (NO) scavenging, metal chelating activity and ferric reducing antioxidant power (FRAP) of GTIN were measured and compared with standards. The flowcytometric analysis and radiation-induced genomic DNA damage by comet assay were employed to estimate the level of intracellular reactive oxygen species (ROS) using isolated murine hepatocytes. RESULTS: GTIN was able to effectively scavenge different free radicals in in vitro situations. It could significantly prevent radiation induced supercoiled and genomic DNA damage with reduced comet parameters. It also acted as a potent scavenger of the radiation induced ROS. CONCLUSIONS: GTIN ameliorated radiation-induced oxidative stress and DNA damage by its free-radical scavenging activity.

Promising role of ferulic acid, atorvastatin and their combination in ameliorating high fat diet-induced stress in mice.

AIMS: The present study evaluated a comparative and combined hepatoprotective effect of atorvastatin (AS) and ferulic acid (F) against high fat diet (HFD) induced oxidative stress in terms of hyperlipidemia, anti-oxidative status, lipid peroxidation and inflammation. MAIN METHODS: Male Swiss albino mice were given a diet containing high fat (H) (23.9% wt/wt), supplemented with AS (10mg/kg) or F (100mg/kg) and both (10 and 100mg/kg) for 8weeks. The control mice (C) were fed with normal diet. KEY FINDINGS: The H mice exhibited increased body weight; hyperlipidemia; serum level of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6); hepatic lipid profile; lipid accumulation; reactive oxygen species (ROS) of hepatocytes, lipid peroxidation and liver antioxidant capacity was decreased. Immunofluorescent and Western blot assay revealed activation of nuclear factor kappa B (NF-κB) signaling pathway. The addition of F or AS and both in the diet significantly counteracted HFD induced body weight gain; hyperlipidemia; TNF-α, IL-6; hepatic lipid profile; fatty infiltration; NF-κB signaling pathway; ROS; lipid peroxidation and moreover elevated levels of hepatic antioxidant enzymes activity were observed. SIGNIFICANCE: Simultaneous treatment with AS, F and their combination protected against HFD induced weight gain and oxidative stress. The protection may be attributed to the hypolipidemic and free radical scavenging activity of AS or F and their combination. This study illustrates that AS and F have relatively similar hypolipidemic, antioxidative, anti-inflammatory actions and the AS+F combination along with HFD has shown outstanding effects as compared to other treated groups.