Palladium Nanoparticles and Lung Health: Assessing Morphology-Dependent Subacute Toxicity in Rats and Toxicity Modulation by Naringin - Paving the Way for Cleaner Vehicular Emissions.

The release of palladium nanoparticles (PdNPs) from autocatalytic converters has raised concerns regarding public health and the environment due to their emergence as anthropogenic contaminants. With growing vehicular population, there is an urgent need for comprehensive toxicological studies of PdNPs to mitigate their risk. The present study aims to investigate the effects of spherical PdNPs with average sizes of 20 and 80 nm, as well as Pd nanorods, on the lung function of female Wistar rats following oral exposure to environmentally relevant doses (1 and 10 µg/kg) over a period of 28 days. Various biological parameters were evaluated, including liver and kidney biochemical changes, lung oxidative stress markers (SOD, CAT, GSH, LPO), lung inflammatory markers (IL-1ß, IL-8, IL-6, and TNF-α), and histopathological alterations in the lungs. Additionally, the potential mitigating effects of naringin on PdNPs-induced toxicity were examined. The results demonstrate a significant increase in oxidative stress, the onset of inflammation, and histological changes in lung alveolar sacs upon exposure to all tested particles. Specifically, 20@PdNPs and PdNRs exhibited higher cytotoxicity and pro-inflammatory properties compared to 80@PdNPs. Naringin effectively attenuated the pulmonary toxicity induced by PdNPs by modulating oxidative and inflammatory pathways. These findings contribute to the sustainable development of PdNPs for their future applications in the biomedical and environmental sectors, ensuring the advancement of safe and sustainable nanotechnology.

Simulating Potential Associated Socio-Economic Determinants With Sustainable Food Security (A Macro-Micro Spatial Quantitative Model).

Improving sustainable food security status, nowadays, is an important challenge globally, especially in developing countries. The policy goal should be equity-everyone has the same opportunity to be food secure-rather than equality-everyone gets the same subsidy. Since the culture and socioeconomic status within a country vary from region to region, collapsing all areas into a unique region may introduce errors and inaccurate results, as most studies carried out. This study assesses the geographical pattern of association between food security and socioeconomic factors in urban areas in Iran using a nationally and regionally representative household consumption-expenditure survey from 2010 to 2018. The logistic regression model and big data are used to achieve this goal. The results show that a substantial number of households face food insecurity in urban areas in Iran. Also, different geographic regions have various salient factors that affect food insecurity. Aggregation tests confirmed that researchers should estimate separate models for different provinces, states, and districts to assess and monitor the food security status of a country instead of estimating a unique model for the whole of the country. Geographical disparities should be considered as an important issue before suggesting any catch-all policies for a country. The geo-locational factor of households is a key determinant of the association between socioeconomic factors and food security in urban areas in Iran. In sum, the practical suggestions for improving Iranian households' food security in urban areas are as follows: (1) Developing job opportunities for the head of household. (2) Enhancing the potential for self-employment. (3) Facilitating the study of children within households including providing inexpensive uniforms, books, and materials, especially for poor households. (4) Supporting young couples in terms of accessing to financial resources and providing inexpensive essential equipment of home for them; and (5) Introduction of the importance of dietary diversity and different foods which can be cooked by using these food ingredients within a household. Comparative case studies using similar methodologies can test if our results are generalizable.

Determinants of household vulnerability to food insecurity during COVID-19 lockdown in a mid-term period in Iran.

OBJECTIVE: This study aimed to identify and rank the different aspects of households' vulnerability to food insecurity. DESIGN: The data were collected by a standard online questionnaire. The Household Food Insecurity Access Scale was used to assess food insecurity levels, and first-order structural equation modelling was applied to determine factors that affect food insecurity. Seven dimensions of vulnerability were measured: economic, social, cultural, human, physical, psychology and information, using thirty-seven items extracted from the related literature review. SETTING: This study was implemented in Tehran province in Iran. PARTICIPANTS: The sample included 392 families residing in Tehran province which was determined using random sampling. RESULTS: About 61 % of the total sample faced food insecurity, at marginal, moderate and severe levels. Economic, psychological and human aspects of vulnerability had the highest effect on food insecurity during the initial COVID-19 lockdown. CONCLUSIONS: Authorities and policymakers must provide economic and financial support to vulnerable households. Abolition of US economic and financial sanctions imposed on Iran must be implemented to battle with COVID-19 in this country.

Spatial analysis of food security in Iran: associated factors and governmental support policies.

This study analyzes caloric intake in Iran as a proxy for food security to determine factors associated with caloric intake that could be impacted by policies. We modeled regional heterogeneity by analyzing a complete countrywide dataset disaggregated for rural intra-provincial areas using unique data from the Iranian Statistical Centre for 2007-2016. We applied logistic regression modeling and likelihood ratio tests to assess the association between socio-economic determinants and caloric intake among rural areas of all provinces. National policies (nation-wide food subsidies and a cash equivalent for food for each adult regardless of residence or income) had significant negative associations with caloric intake among all provinces. The detected spatial diversity suggests policies specific to each area could be more effective than a centralized national policy for food security. Rather than implementing one-size-fits-all policies, such as across-the-board cash food subsidies, the government should take a differential spatially targeted approach to directly support low-income households.

Impact of Emotional Support, Informational Support, and Norms of Reciprocity on Trust Toward the Medical Aesthetic Community: The Moderating Effect of Core Self-Evaluations.

BACKGROUND: The consumption of medical aesthetic services has become popular in recent years. Many people have purchased medical aesthetic services and treatments in pursuit of self-beauty. When members of online medical aesthetic communities actively participate in discussions and encourage and support one another, there is an increase in community commitment, trust toward each other, and trust toward the community, ultimately promoting social sharing in an environment of positive feedback. OBJECTIVE: This study aimed to explore via the theory of social support-grounded in a deeper social capabilities framework developed by Khan following the Nobel laureate Amartya Sen's groundbreaking work-whether emotional support, informational support, and norms of reciprocity in online communities impact group members in terms of creating trust toward other members. This enhances trust toward the community and generates a sense of community commitment, ultimately impacting social buying intention and social sharing intention. METHODS: This study used IBM SPSS and AMOS to analyze data. Data were collected through online questionnaires in online medical aesthetic community forums, thereby producing samples that were both representative and accurate. To understand whether core self-evaluation (CSE) is a moderator in the relationship between social sharing intention and social buying intention, this study averaged the point of CSEs in the sample after statistical analysis, dividing the sample into 2 groups. RESULTS: The results showed that emotional support and norms of reciprocity positively impact trust toward members, and trust toward members positively impact trust toward the community. This generates trust transfer, which positively impacts social buying intention and social sharing intention. At the same time, CSE is a moderator variable between trust toward the community and social buying intention, but CSE is not a moderator variable between trust toward the community and social sharing intention. CONCLUSIONS: This study revealed that when members of online medical aesthetic communities actively participate in discussions and encourage and support one another, community commitment, trust toward each other, and trust toward the community increases, ultimately promoting social sharing and buying intentions.

Amelioration of oxidative stress in the joint tissue may be the basis for the antiarthritic activity of Terminalia arjuna bark extract.

AIM: In this study we have evaluated the antioxidant and antiarthritic activity of Terminalia arjuna bark extract (TABE) in collagen-induced arthritis (CIA) in rats. METHODS: Arthritis was induced in rats by intradermal injection of the collagen-complete Freund's adjuvant emulsion. Right hind paw thickness was measured as a primary marker for severity of arthritis. Biochemical parameters such as tissue levels of superoxide dismutase (SOD), catalase, reduced glutathione (GSH), nitrites and thiobarbituric acid reactive substances (TBARS) were measured to determine the effect of treatment on antioxidant defenses. Articular elastase (ELA) level in the arthritic tissue was measured as a marker for neutrophil infiltration. RESULT: Terminalia arjuna bark extract administration significantly inhibited the increase in paw thickness induced by immunization with collagen as compared to CIA-control animals. Further, it attenuated the fall in tissue SOD and GSH levels and mitigated the increase in tissue nitrites and TBARS levels as compared to CIA-control animals. Tissue ELA levels, which were significantly increased in the CIA-control animals as compared to normal animals were also significantly reduced by TABE administration. CONCLUSION: Results of our study demonstrate the antioxidant and antiarthritic activity of TABE in CIA in rats. We believe that TABE could find clinical application in the management of rheumatoid arthritis and associated disorders.

Yohimbine hydrochloride ameliorates collagen type-II-induced arthritis targeting oxidative stress and inflammatory cytokines in Wistar rats.

Rheumatoid arthritis (RA) is the most common type of chronic inflammatory disease which is triggered by dysfunction in the immune system which in turn affects synovial joints. Current treatment of RA with NSAIDs and DMRDs is limited by their side effect. As a result, the interest in alternative, well tolerated anti-inflammatory remedies has re-emerged. Our aim was to evaluate the antioxidant and anti-inflammatory activities underlying the anti-RA effect of Yohimbine hydrochloride (YCL) in collagen induced arthritis (CIA) in Wistar rats. The YCL was administered at doses of 5 and 10 mg kg-1 body weight once daily for 28 days. The effects of treatment in the rats were assessed by biochemical parameter (articular elastase, LPO, GSH, catalase, SOD), hematological parameter (ESR, WBC, C-reactive protein (CRP), immunohistochemical expression (COX2, TNF-α, and NF-κB), and histological changes in joints. YCL showed anti-RA efficacy as it significantly reduced articular elastase, LPO and catalase level and ameliorates histological changes. This is in addition to its antioxidant efficacy as YCL shown a significant increase in GSH and SOD level. Also, YCL showed effective anti-inflammatory activity as it significantly decreased the expression of COX-2, TNF-α, and NF-ĸB. The therapeutic effect of YCL against RA was also evident from lower arthritis scoring and reduced hematological parameter (ESR, WBC, and C-reactive protein level). The abilities to inhibit proinflammatory cytokines and modulation of antioxidant states that the protective effect of YCL on arthritis rats might be mediated via the modulation of the immune system. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 619-629, 2017.

Accumulation of reactivity to MBP sensitizes TRAIL mediated oligodendrocyte apoptosis in adult sub cortical white matter in a model for human multiple sclerosis.

Reactivity to myelin associated proteins is the hallmark of human multiple sclerosis (M.S) and its experimental counterparts. However, the nature of such reactivity has not been described fully. Herein, we report that myelin basic protein (MBP) reactivity accumulates in a rat model for M.S. over a period of time and sensitizes TRAIL mediated progressive oligodendrocyte apoptosis. We used active immunization by Myelin Oligodendrocyte Glycoprotein (MOG, 50 µg) to study chronic remitting relapsing encephalomyelitis in rats. A time point analysis of the progressive disease revealed cumulative accumulation of anti myelin basic protein antibodies during the disease progression with minimal change in the anti-MOG antibodies. Increased reactivity to MBP was studied to sensitize TNF related apoptosis-inducing ligand (TRAIL) and other proinflammatory cytokines in a cumulative fashion leading to the Caspase dependent apoptosis of oligodendrocytes and myelin loss. In a rescue experiment, we could limit the demyelination and prevent disease progression by neutralizing the effector, TRAIL in an early stage of the disease. This is the first study to identify the accumulation of MBP antibodies in MOG induced EAE which possibly leads to TRAIL sensitized oligodendrocyte apoptosis in the white mater of EAE rats. This finding stresses on the need to study MBP antibody titers in M.S. patients and therefore might serve as an alternate marker for progressive demyelination.

Effect of cadmium chloride exposure during the induction of collagen induced arthritis.

The precise cause of autoimmune diseases such as rheumatoid arthritis remains uncertain. Collagen induced arthritis (CIA) in animals is the most commonly used model of human rheumatoid arthritis (RA). Exposure of humans and animals to toxic metals is widespread. Cadmium is one of the most prevalent nephrotoxic heavy metal, but it may cause other systemic toxicity as well. Cadmium may cause adverse health effects by impairment of the immune systems and induction of reactive oxygen species. Since rheumatoid arthritis pathogenesis involve immune system disorder and chronic inflammation, the present study has been designed to find out the effect of cadmium chloride exposure on clinical manifestation of development of collagen induced rheumatoid arthritis. Arthritis was induced in rats by intradermal injection of emulsion of type II collagen in Complete Freund's Adjuvant. Rats were treated with cadmium chloride dissolved in drinking water at concentrations of 5ppm and 50ppm for 21 days from day of immunization. The effects of cadmium in the rats were assessed by biochemical parameters (articular elastase, articular nitrite, lipid peroxidation, reduced glutathione, catalase and superoxide dismutase) histopathological analysis and immunohistochemical expression of pro-inflammatory cytokines in rat joint tissue. Histopathological changes further confirmed the biochemical and immunohistochemical results. Our results suggest that exposure to cadmium chloride during the induction phase of collagen induced arthritis abrogate disease development at lower dose whereas exacerbates at higher dose in Wistar rats.

Boswellia serrata extract attenuates inflammatory mediators and oxidative stress in collagen induced arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease which leads to destruction of joints. Current treatment modalities for RA either produce symptomatic relief (NSAIDs) or modify the disease process (DMARDs). Though effective, their use is also limited by their side effects. As a result, the interest in alternative, well tolerated anti-inflammatory remedies has re-emerged. Our aim was to evaluate the antioxidant and antiarthritic activity of Boswellia serrata gum resin extract (BSE) in collagen induced arthritis. Arthritis was induced in male Wistar rats by collagen induced arthritis (CIA) method. BSE was administered at doses of 100 and 200mg/kg body weight once daily for 21 days. The effects of treatment in the rats were assessed by biochemical (articular elastase, MPO, LPO, GSH, catalase, SOD and NO), inflammatory mediators (IL-1ß, IL-6, TNF-α, IL-10, IFN-γ and PGE2), and histological studies in joints. BSE was effective in bringing significant changes on all the parameters (articular elastase, MPO, LPO, GSH, catalase, SOD and NO) studied. Oral administration of BSE resulted in significantly reduced levels of inflammatory mediators (IL-1ß, IL-6, TNF-α, IFN-γ and PGE2), and increased level of IL-10. The protective effects of BSE against RA were also evident from the decrease in arthritis scoring and bone histology. The abilities to inhibit proinflammatory cytokines and modulation of antioxidant status suggest that the protective effect of Boswellia serrata extract on arthritis in rats might be mediated via the modulation of immune system.

Ultrasound assisted dispersive liquid-liquid microextraction followed by injector port silylation: a novel method for rapid determination of quinine in urine by GC-MS.

BACKGROUND: Silylation is a widely used derivatization method for the analysis of polar analytes by GC-MS. Ultrasound-assisted dispersive liquid-liquid microextraction (UA-DLLME) is an ecofriendly, rapid and simple microextraction method. For the first time, a novel approach has been developed and applied for the analysis of quinine in urine by combining UA-DLLME with injection port silylation. RESULTS: The LOD and LOQ were found to be 5.4 and 18 ng/ml. The intra- and inter-day precisions were less than 5 and 8%, respectively. Mean recoveries of quinine were found to be in the range of 87 to 96%. CONCLUSION: Ultrasound-assisted dispersive liquid-liquid microextraction is rapid, simple and consumes less reagent for the analysis of polar analytes such as quinine.

Piperine ameliorates oxidative stress, inflammation and histological outcome in collagen induced arthritis.

OBJECTIVES: Piperine, a main component of Piper species, is a plant alkaloid with a long history of medical use in a variety of inflammatory disorders like rheumatoid arthritis. Due to side effects in current treatment modalities of rheumatoid arthritis, the interest in alternative, well tolerated anti-inflammatory remedies has re-emerged. The aim of this work was to evaluate the anti-inflammatory and antiarthritic effects of piperine. METHODS: Arthritis was induced in male Wistar rats by collagen induced arthritis (CIA) method. Piperine was administered at a dose of 100mgkg(-1) and indomethacin at 1mgkg(-1) body weight once daily for 21days. The effects of treatment in the rats were assessed by biochemical (articular elastase, MPO, LPO, GSH, Catalase, SOD and NO), inflammatory mediators (IL-1ß, TNF-α, IL-10 and PGE2) and histological studies in joints. RESULTS: Piperine was effective in bringing significant changes on all the parameters (articular elastase, MPO, LPO, GSH, Catalase, SOD and NO) studied. Oral administration of piperine resulted in significantly reduced the levels of pro-inflammatory mediators (IL-1ß, TNF-α and PGE2) and increased level of IL-10. The protective effects of piperine against RA were also evident from the decrease in arthritis scoring and bone histology. CONCLUSIONS: In conclusion, the fact that piperine alter a number of factors known to be involved in RA pathogenesis indicates that piperine can be used similar to indomethacin as a safe and effective therapy for CIA and may be useful in the treatment of rheumatoid arthritis.

Simultaneous derivatisation and preconcentration of parabens in food and other matrices by isobutyl chloroformate and dispersive liquid-liquid microextraction followed by gas chromatographic analysis.

A simple, rapid and economical method has been proposed for the quantitative determination of parabens (methyl, ethyl, propyl and butyl paraben) in different samples (food, cosmetics and water) based on isobutyl chloroformate (IBCF) derivatisation and preconcentration using dispersive liquid-liquid microextraction in single step. Under optimum conditions, solid samples were extracted with ethanol (disperser solvent) and 200 µL of this extract along with 50 µL of chloroform (extraction solvent) and 10 µL of IBCF was rapidly injected into 2 mL of ultra-pure water containing 150 µL of pyridine to induce formation of a cloudy state. After centrifugation, 1 µL of the sedimented phase was analysed using gas chromatograph-flame ionisation detector (GC-FID) and the peaks were confirmed using gas chromatograph-positive chemical ionisation-mass spectrometer (GC-PCI-MS). Method was found to be linear over the range of 0.1-10 µg mL(-1) with square of correlation coefficient (R(2)) in the range of 0.9913-0.9992. Limit of detection (LOD) and limit of quantification (LOQ) were found to be 0.029-0.102 µg mL(-1) and 0.095-0.336 µg mL(-1) with a signal to noise ratio of 3:1 and 10:1, respectively.

In matrix derivatization of trichloroethylene metabolites in human plasma with methyl chloroformate and their determination by solid-phase microextraction-gas chromatography-electron capture detector.

Trichloroethylene (TCE) is a common industrial chemical that has been widely used as metal degreaser and for many industrial purposes. In humans, TCE is metabolized into dichloroacetic acid (DCA), trichloroacetic acid (TCA) and trichloroethanol (TCOH). A simple and rapid method has been developed for the quantitative determination of TCE metabolites. The procedure involves the in situ derivatization of TCE metabolites with methyl chloroformate (MCF) directly in diluted plasma samples followed by extraction and analysis with solid-phase microextraction (SPME) coupled to gas chromatography-electron capture detector (GC-ECD). Factors which can influence the efficiency of derivatization such as amount of MCF and pyridine (PYR), ratio of water/methanol were optimized. The factors which can affect the extraction efficiencies of SPME were screened using 2(7-4) Placket-Burman Design (PBD). A central composite design (CCD) was then applied to further optimize the most significant factors for optimum SPME extraction. The optimum factors for the SPME extraction were found to be 562.5mg of NaCl, pH at 1 and an extraction time of 22 min. Recoveries and detection limits of all three analytes in plasma were found to be in the range of 92.69-97.55% and 0.036-0.068 µg mL(-1) of plasma, respectively. The correlation coefficients were found to be in the range of 0.990-0.995. The intra- and inter-day precisions for TCE metabolites were found to be in the range of 2.37-4.81% and 5.13-7.61%, respectively. The major advantage of this method is that MCF derivatization allows conversion of TCE metabolites into their methyl esters in very short time (≤30 s) at room temperature directly in the plasma samples, thus makes it a solventless analysis. The method developed was successfully applied to the plasma samples of humans exposed to TCE.

Quercetin prevents protein nitration and glycolytic block of proliferation in hydrogen peroxide insulted cultured neuronal precursor cells (NPCs): Implications on CNS regeneration.

Survival along with optimal proliferation of neuronal precursors determines the outcomes of the endogenous cellular repair in CNS. Cellular-oxidation based cell death has been described in several neurodegenerative disorders. Therefore, this study was aimed at the identification of the potent targets of oxidative damage to the neuronal precursors and its effective prevention by a natural flavonoid, Quercetin. Neuronal precursor cells (NPCs), Nestin+ and GFAP (Glial fibrillary acidic protein)+ were isolated and cultured from adult rat SVZ (subventricular zone). These cells were challenged with a single dose of H2O2 (50µM) and/or pre-treated with different concentrations of Quercetin. H2O2 severely limited the cellular viability and expansion of the neurospheres. Cellular-oxidation studies revealed reduction in glutathione dependent redox buffering along with depletion of enzymatic cellular antioxidants that might potentiate the nitrite (NO2(-)) and superoxide anion (O2(-)) mediated peroxynitrite (ONOO(-)) formation and irreversible protein nitration. We identified depleted PK-M2 (M2 isoform of pyruvate kinase) activity and apoptosis of NPCs revealed by the genomic DNA fragmentation and elevated PARP (poly ADP ribose polymerase) activity along with increased Caspase activity initiated by severely depolarised mitochondrial membranes. However, the pre-treatment of Quercetin in a dose-response manner prevented these changes and restored the expansion of neurospheres preferably by neutralizing the oxidative conditions and thereby reducing peroxynitrite formation, protein nitration and PK-M2 depletion. Our results unravel the potential interactions of oxidative environment and respiration in the survival and activation of precursors and offer a promise shown by a natural flavonoid in the protective strategy for neuronal precursors of adult brain.

Hesperidin inhibits collagen-induced arthritis possibly through suppression of free radical load and reduction in neutrophil activation and infiltration.

Rheumatoid arthritis is a chronic inflammatory disease characterized by the destruction of articular cartilage and bone in a chronic phase. Pathology of rheumatoid arthritis suggests autoimmunity linked to inflammation. In our study, rheumatoid arthritis was induced in Wistar rats by intradermal injections of 100 µl of emulsion containing bovine type II collagen in complete Freund's adjuvant at the base of the tail. Disease developed about 13 ± 1 days after immunization and treatment with hesperidin (HES) at a dose of 160 mg kg(-1) body weight was given after onset of disease daily until 20th day. The effect of treatment in the rats was monitored by clinical scoring, biochemical parameters and histological evaluations in joints. A steady increase in the articular elastase, nitric oxide and lipid peroxidation was observed in joints of arthritic rats as compared to control, whereas a significant decrease in reduced glutathione, superoxide dismutase activity and catalase was observed in collagen-induced arthritis rats as compared to control group. The results from the present work indicate that the treatment with hesperidin was effective in bringing about significant changes on all the parameters studied in collagen-induced arthritis rats. These data confirm that erosive destruction of the joint cartilage in collagen-induced arthritis is due free radicals released by activated neutrophils and produced by other biochemical pathways. In the present study, an attempt has been made to amelioration of the disease process by a natural product. These results suggest that oral administration of HES could be effective for treating human RA patients.

Low density solvent based dispersive liquid-liquid microextraction with gas chromatography-electron capture detection for the determination of cypermethrin in tissues and blood of cypermethrin treated rats.

A simple and rapid method to determine the cypermethrin (CYP) insecticide in rat tissues (kidney, liver and brain) and blood has been developed for the first time using low density solvent-dispersive liquid-liquid microextraction (LDS-DLLME) followed by gas chromatography-electron capture detector (GC-ECD) analysis. Initially, tissue samples containing CYP were homoginized in acetone. Subsequently, homogenate was mixed with n-hexane (extraction solvent) and the mixture was rapidly injected into water. The upper n-hexane layer was collected in a separate microtube and injected into GC-ECD for analysis. Blood samples were diluted with ultrapure water and subjected to DLLME through similar procedure. Parameters such as type and volume of disperser and extraction solvent, salting out effect and extraction time, which can affect the extraction efficiency of DLLME, were optimized. Method was validated by investigating linearity, precision, recovery, limit of detection (LOD) and quantification (LOQ). LODs in tissue were in the range of 0.043-0.314 ng mg(-1) and for blood it was 8.6 ng mL(-1) with a signal to noise ratio of 3:1. LOQs in tissue were in the range of 0.143-1.03 ng mg(-1) and for blood it was 28.3 ng mL(-1) with a signal to noise ratio of 10:1. Mean recoveries of CYP at three different concentation levels in all the matrices were found to be in the range of 81.6-103.67%. The results show that, LDS-DLLME coupled with GC-ECD offers a simple, rapid and efficient technique for extraction and determination of CYP in rat tissues and blood samples, which in turn would be useful for toxicological studies of CYP.

Modulation of the oxidative stress and inflammatory cytokine response by thymoquinone in the collagen induced arthritis in Wistar rats.

Thymoquinone (TQ) is the major active compound derived from Nigella sativa. Our aim of this work was to evaluate the antioxidant and antiarthritic activity of TQ in Wistar rat by collagen induced arthritis (CIA). TQ was administered at a dose of 5mgkg(-1) body weight once daily for 21days. The effects of treatment in the rats were assessed by biochemical (articular elastase, MPO, LPO, GSH, catalase, SOD and NO), inflammatory mediators (IL-1ß, IL-6, TNF-α, IL-10, IFN-γ and PGE(2)) and histological studies in joints. TQ was effective in bringing significant changes on all the parameters (articular elastase, MPO, LPO, GSH, catalase, SOD and NO) studied. Oral administration of TQ resulted in significantly reduced the levels of pro-inflammatory mediators (IL-1ß, IL-6, TNF-α, IFN-γ and PGE(2)) and increased level of IL-10. The protective effects of TQ against RA were also evident from the decrease in arthritis scoring and bone histology. In conclusion, the fact that TQ abolished a number of factors known to be involved in RA pathogenesis indicates that the administration of thymoquinone may have potential value in the treatment of inflammatory disease.

Scorpion venom (Odontobuthus doriae) induces apoptosis by depolarization of mitochondria and reduces S-phase population in human breast cancer cells (MCF-7).

Venom of some species of scorpions induces apoptosis and arrests proliferation in cancer cells. This is an important property that can be harnessed and can lead to isolation of compounds of therapeutic importance in cancer research. Cytotoxicity was investigated using MTT reduction and confirmed with lactate dehydrogenase release following venom exposure. Apoptosis was evaluated with determination of mitochondrial membrane potential, reactive nitrogen species assay, measurement of Caspase-3 activity and DNA fragmentation analysis. To confirm that venom can inhibit DNA synthesis in proliferating breast cancer cells, immunocytochemical detection of BrdU incorporation was done. Our results demonstrated that venom of Odontobuthus doriae not only induced apoptosis but lead to the inhibition of DNA synthesis in human breast cancer cells (MCF-7). Cell viability decreased with parallel increment of LDH release in dose dependent manner after treatment with varying concentrations of venom. Moreover, venom depleted cellular antioxidants evidenced by depression of GSH and Catalases and concomitantly increased reactive nitrogen intermediates (RNI). These events were related to the depolarization of mitochondria and associated Caspase-3 activation following venom treatment in a concentration dependent manner. Finally, fragmentation of nuclear DNA following venom treatment confirmed the apoptotic property of the said venom. These results suggest that venom of O. doriae can be potential source for the isolation of effective anti-proliferative and apoptotic molecules.