Assessment of Silver Nanoparticles Derived from Brown Algae Sargassum vulgare: Insight into Antioxidants, Anticancer, Antibacterial and Hepatoprotective Effect.

Algae are used as safe materials to fabricate novel nanoparticles to treat some diseases. Marine brown alga Sargassum vulgare are used to fabricate silver nanoparticles (Sv/Ag-NPs). The characterization of Sv/Ag-NPs was determined by TEM, EDX, Zeta potential, XRD, and UV spectroscopy. The Sv/Ag-NPs were investigated as antioxidant, anticancer, and antibacterial activities against Gram-positive bacteria Bacillus mojavensis PP400982, Staphylococcus caprae PP401704, Staphylococcus capitis PP402689, and Staphylococcus epidermidis PP403851. The activity of the Sv/Ag-NPs was evaluated as hepatoprotective in vitro in comparison with silymarin. The UV-visible spectrum of Sv/Ag-NPs appeared at 442 nm; the size of Sv/Ag-NPs is in range between 6.90 to 16.97 nm, and spherical in shape. Different concentrations of Sv/Ag-NPs possessed antioxidant, anticancer activities against (HepG-2), colon carcinoma (HCT-116), cervical carcinoma (HeLa), and prostate carcinoma (PC-3) with IC50 50.46, 45.84, 78.42, and 100.39 µg/mL, respectively. The Sv/Ag-NPs induced the cell viability of Hep G2 cells and hepatocytes treated with carbon tetrachloride. The Sv/Ag-NPs exhibited antibacterial activities against Staphylococcus caprae PP401704, Staphylococcus capitis PP402689, and Staphylococcus epidermidis PP403851. This study strongly suggests the silver nanoparticles derived from Sargassum vulgare showed potential hepato-protective effect against carbon tetrachloride-induced liver cells, and could be used as anticancer and antibacterial activities.

Assessment of the ameliorative effect of curcumin on pendimethalin-induced genetic and biochemical toxicity.

The present study aimed to assess the toxic effects of pendimethalin herbicide and protective role of curcumin using the Allium test on cytological, biochemical and physiological parameters. The effective concentration (EC50) of pendimethalin was determined at 12 mg/L by the root growth inhibition test as the concentration reducing the root length by 50%. The roots of Allium cepa L. was treated with tap water (group I), 5 mg/L curcumin (group II), 10 mg/L curcumin (group III), 12 mg/L pendimethalin (group IV), 12 mg/L pendimethalin + 5 mg/L curcumin (group V) and 12 mg/L pendimethalin + 10 mg/L curcumin (group VI). The cytological (mitotic index, chromosomal abnormalities and DNA damage), physiological (rooting percentage, root length, growth rate and weight gain) and oxidative stress (malondialdehyde level, superoxide dismutase level, catalase level and glutathione reductase level) indicators were determined after 96 h of treatment. The results revealed that pendimethalin treatment reduced rooting percentage, root length, growth rate and weight gain whereas induced chromosomal abnormalities and DNA damage in roots of A. cepa L. Further, pendimethalin exposure elevated malondialdehyde level followed by antioxidant enzymes. The activities of superoxide dismutase and catalase were up-regulated and glutathione reductase was down-regulated. The molecular docking supported the antioxidant enzymes activities result. However, a dose-dependent reduction of pendimethalin toxicity was observed when curcumin was supplied with pendimethalin. The maximum recovery of cytological, physiological and oxidative stress parameters was recorded at 10 mg/L concentration of curcumin. The correlation studies also revealed positive relation of curcumin with rooting percentage, root length, weight gain, mitotic activity and glutathione reductase enzyme level while an inverse correlation was observed with chromosomal abnormalities, DNA damage, superoxide dismutase and catalase enzyme activities, and lipid peroxidation indicating its protective effect.

Combined In Silico, Ex Vivo, and In Vivo Assessment of L-17, a Thiadiazine Derivative with Putative Neuro- and Cardioprotective and Antidepressant Effects.

Depression associated with poor general medical condition, such as post-stroke (PSD) or post-myocardial infarction (PMID) depression, is characterized by resistance to classical antidepressants. Special treatment strategies should thus be developed for these conditions. Our study aims to investigate the mechanism of action of 2-morpholino-5-phenyl-6H-1,3,4-thiadiazine, hydrobromide (L-17), a recently designed thiadiazine derivative with putative neuro- and cardioprotective and antidepressant-like effects, using combined in silico (for prediction of the molecular binding mechanisms), ex vivo (for assessment of the neural excitability using c-Fos immunocytochemistry), and in vivo (for direct examination of the neuronal excitability) methodological approaches. We found that the predicted binding affinities of L-17 to serotonin (5-HT) transporter (SERT) and 5-HT3 and 5-HT1A receptors are compatible with selective 5-HT serotonin reuptake inhibitors (SSRIs) and antagonists of 5-HT3 and 5-HT1A receptors, respectively. L-17 robustly increased c-Fos immunoreactivity in the amygdala and decreased it in the hippocampus. L-17 dose-dependently inhibited 5-HT neurons of the dorsal raphe nucleus; this inhibition was partially reversed by the 5-HT1A antagonist WAY100135. We suggest that L-17 is a potent 5-HT reuptake inhibitor and partial antagonist of 5-HT3 and 5-HT1A receptors; the effects of L-17 on amygdaloid and hippocampal excitability might be mediated via 5-HT, and putatively mediate the antidepressant-like effects of this drug. Since L-17 also possesses neuro- and cardioprotective properties, it can be beneficial in PSD and PMID. Combined in silico predictions with ex vivo neurochemical and in vivo electrophysiological assessments might be a useful strategy for early assessment of the efficacy and neural mechanism of action of novel CNS drugs.

Assessment of renal and hepato-protective potential of guava leaves in male Sprague dawley rats.

Present research project was an attempt to explore the functional/nutraceutical worth of guava leaves from two locally grown varieties (Ruby & Safeda). For the purpose, guava leaves extract was fed to experimental male Sprague Dawley rats to explore the nutraceutical potential of guava leaves against hepatotoxicity. Two studies were performed on two types of rats i.e. study I (normal rats), study II (hepatotoxic rats). In both studies, 250 mg/kg each of pink guava leaves extracts (T1) and white guava leaves extracts (T2) was added in the feed. Feed intake and body weights of the rats were recorded. At the end of the first and eighth week of study, the blood samples of the rats were analyzed to check the effect of guava leaves extracts on renal functioning (Alkaline Phosphatase, Alanine Transaminase and Aspartate Transaminase) as well as liver functioning parameters including urea and creatinine. In both studies, comparatively higher feed consumption was observed in the control group than the rest of the treatments. At the end of study I, the highest weight (207±9.21 g) was observed in T0 whereas, during study II, the maximum value (202±5.58 g) was found in T2 (rats consuming white guava leaves extract) that indicates its effectiveness against hepatotoxicity. Regarding renal functioning tests, pink guava leaves were more effective in decreasing urea and creatinine levels in rats as compared to the white guava leaves in both study plans. Likewise, in each of study trial, pink guava leaves were more effective in reducing AST, ALT and ALP than white guava leaves and control. From the present investigation, it is deduced that guava leaves were effective against hepatotoxicity.

Assessment of the Cytoprotective Effects of High-Dose Valproic Acid Compared to a Clinically Used Lower Dose.

OBJECTIVE: Valproic acid (VPA) treatment improves survival in animal models of injuries on doses higher than those allowed by Food and Drug Administration (FDA). We investigated the proteomic alterations induced by a single high-dose (140mg/kg) of VPA (VPA140) compared to the FDA-approved dose of 30mg/kg (VPA30) in healthy humans. We also describe the proteomic and transcriptomic changes induced by VPA140 in an injured patient. We hypothesized that VPA140 would induce cytoprotective changes in the study participants. METHODS: Serum samples were obtained from healthy subjects randomized to two groups; VPA140 and VPA30 at 3 timepoints: 0h(baseline), 2h, and 24h following infusion(n = 3/group). Samples were also obtained from an injured patient that received VPA140 at 0h, 6h and 24h following infusion. Proteomic analyses were performed using liquid chromatography-mass spectrometry (LC-MS/MS), and transcriptomic analysis was performed using RNA-sequencing. Differentially expressed (DE) proteins and genes were identified for functional annotation and pathway analysis using iPathwayGuide and gene set enrichment analysis (GSEA), respectively. RESULTS: For healthy individuals, a dose comparison was performed between VPA140 and VPA30 groups at 2 and 24 h. Functional annotation showed that top biological processes in VPA140 versus VPA30 analysis at 2 h included regulation of fatty acid (P = 0.002) and ATP biosynthesis (P = 0.007), response to hypoxia (P = 0.017), cell polarity regulation (P = 0.031), and sequestration of calcium ions (P = 0.031). Top processes at 24 h in VPA140 versus VPA30 analysis included amino acid metabolism (P = 0.023), collagen catabolism (P = 0.023), and regulation of protein breakdown (P = 0.023). In the injured patient, annotation of the DE proteins in the serum showed that top biological processes at 2 h included neutrophil chemotaxis (P = 0.002), regulation of cellular response to heat (P = 0.008), regulation of oxidative stress (P = 0.008) and regulation of apoptotic signaling pathway (P = 0.008). Top biological processes in the injured patient at 24 h included autophagy (P = 0.01), glycolysis (P = 0.01), regulation of apoptosis (P = 0.01) and neuron apoptotic processes (P = 0.02). CONCLUSIONS: VPA140 induces cytoprotective changes in human proteome not observed in VPA30. These changes may be responsible for its protective effects in response to injuries.

Pleiotropic Effects of Eugenol: The Good, the Bad, and the Unknown.

Phytocompounds and medicinal herbs were used in traditional ancient medicine and are nowadays increasingly screened in both experimental and clinical settings due to their beneficial effects in several major pathologies. Similar to the drug industry, phytotherapy is interested in using nanobased delivery systems to view the identification and characterization of the cellular and molecular therapeutic targets of plant components. Eugenol, the major phenolic constituent of clove essential oil, is a particularly versatile phytochemical with a vast range of therapeutic properties, among which the anti-inflammatory, antioxidant, and anticarcinogenic effects have been systematically addressed. In the past decade, with the emerging understanding of the role of mitochondria as critical organelles in the pathophysiology of noncommunicable diseases, research regarding the role of phytochemicals as modulators of bioenergetics and metabolism is on a rise. Here, we present a brief overview of the major pharmacological properties of eugenol, with special emphasis on its applications in dental medicine, and provide preliminary data regarding its effects, alone, and included in polyurethane nanostructures, on mitochondrial bioenergetics, and glycolysis in human HaCaT keratinocytes.

Novel peripheral role of Nurr-1/GDNF/AKT trajectory in carvedilol and/or morin hydrate hepatoprotective effect in a model of hepatic ischemia/reperfusion.

Although the central role of Nurr-1/GDNF has been reviewed amply, scarce data are available on their peripheral impact. Carvedilol and morin hydrate have previously conferred their hepatic anti-fibrotic action. AIM: Thus, our aim was to unveil the potential hepatoprotective role of carvedilol (CR) and/or morin hydrate (MH) using a hepatic 70% partial warm ischemia/reperfusion (I/R) rat model. MAIN METHOD: Rats were allocated into sham-operated, hepatic I/R, and I/R preceded by oral administration of CR (10 and 30 mg/kg; CR10/CR30), MH (30 mg/kg), or CR10 + MH for one week. KEY FINDINGS: On the molecular level, pretreatment with CR and/or MH increased the hepatic contents of Nurr-1, GDNF, and the protein expression of active/p-AKT. On the other hand, they inactivated GSK3ß and NF-κB to increase the antioxidant enzymes (GPx, SOD, CAT). All regimens also enhanced the autophagy/lysosomal function and boosted the protein expression of beclin-1, LC3II, and TFEB. Moreover, their antiapoptotic effect was signified by increasing the anti-apoptotic molecule Bcl2 and inhibiting Bax, Bax/Bcl2 ratio, and caspase-3, effects that were confirmed by the TUNEL assay. These improvements were reflected on liver function, as they decreased serum aminotransferases and liver structural alterations induced by I/R. Despite its mild impact, CR10 showed marked improvements when combined with MH; this synergistic interaction overrides the effect of either regimen alone. SIGNIFICANCE: In conclusion, CR, MH, and especially the combination regimen, conferred hepatoprotection against I/R via activating the Nurr-1/GDNF/AKT trajectory to induce autophagy/lysosomal biogenesis, inhibit GSK3ß/NF-кB hub and apoptosis, and amend redox balance.

Hepatoprotective activity assessment of amino acids derivatives of picroside I and II.

Picrorhiza kurroa has a long medicinal history as a traditional medicinal plant in China and India that is widely used in clinical treatments. It is a common treatment for liver diseases, fever, diarrhoea, indigestion, and some other diseases. Modern pharmacological studies proved that P. kurroa rhizomes have high levels of picroside I and II, which were identified as main constituents with anti-inflammatory and hepatoprotective activities. In our study, we used picroside I and II as the lead compounds to generate derivatives by reactions with Boc-valine or Boc-proline, which underwent dehydration and condensation with the hydroxyl groups in the lead compounds in the presence of coupling reagent N,N'-dicyclohexylcarbodiimide. We synthesized 11 derivatives and examined their hepatoprotective effects in vitro by assessing the proliferation rates of H2 O2 -exposed HepG2 cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. We found that some derivatives promoted higher proliferation rates in HepG2 cells than the natural compounds before derivatization, suggesting that those derivatives possessed an improved hepatoprotective capacity. The novel derivatization strategy for picrosides had the additional benefit that the esterification of their hydroxyl groups created derivatives not only with increased stability but also with improved pharmacokinetic properties and potentially prolonged half-life.

Assessment of α-amanitin toxicity and effects of silibinin and penicillin in different in vitro models.

Silibinin (Sil) is used as hepatoprotective drug and is approved for therapeutic use in amanitin poisoning. In our study we compared Sil-bis-succinate (SilBS), a water-soluble drug approved for i.v.-administration, with Sil solved in ethanol (SilEtOH), which is normally used in research. We challenged monocultures or 3D-microtissues consisting of HepG2 cells or primary hepatocytes with α-amanitin and treated with SILBS, SILEtOH, penicillin and combinations thereof. Cell viability and the integrity of the microtissues was monitored. Finally, the expression of the transporters OATP1B1 and B3 was analyzed by qRT-PCR. We demonstrated that primary hepatocytes were more sensitive to α-amanitin compared to HepG2. Primary hepatocytes cultures were protected by SilBS and SilEtOH independent of penicillin from the cytotoxic effects of α-amanitin. Subsequent studies of the expression profile of the transporters OATP1B1/B3 revealed that primary hepatocytes do express both whereas in HepG2 cells they were hardly detectable. Our study showed that SilBS has significant advantage over SilEtOH with no additional benefit of penicillin. Moreover, HepG2 cells may not represent an appropriate model to investigate Amanita phalloides poisoning in vitro with focus on OATP transporters since these cells are lacking sensitivity towards α-amanitin probably due to missing cytotoxicity-associated transporters suggesting that primary hepatocytes should be preferred in this context.

Comparative assessment of the effects of meso-2,3-dimercaptosuccinic acid and salinomycin on spleen function of cadmium-exposed mice.

In this study, we present experimental data on the effects of meso-2,3-dimercaptosuccinic acid (DMSA) and tetraethylammonium salt of salinomycinic acid (Sal) on cadmium-induced spleen dysfunction and altered essential metal balance in mice. Sixty-day-old male mice (ICR line) were randomly divided into four groups: untreated control group (Ctrl)-obtained distilled water for 28 days, toxic control group (Cd)-exposed to cadmium acetate dihydrate at average daily dose of 20mg/kg body weight (BW) for 14 days, Cd + DMSA group-obtained cadmium acetate dihydrate as the toxic control group followed by treatment with 20mg/kg BW DMSA for 2 weeks, and Cd + Sal group-mice exposed to cadmium acetate dihydrate at average daily dose of 20mg/kg BW for 2 weeks followed by administration of Sal at an average daily dose of 20mg/kg BW for 2 weeks. The compounds were administered orally via the drinking water of the animals. We found that cadmium exposure caused splenomegaly and reduced the hemoglobin and hematocrit levels and total red blood cell count compared with untreated controls. Cadmium intoxication of mice induced accumulation of the toxic metal ion in the blood and spleen. Alterations in the endogenous levels of calcium (Ca) and iron (Fe) in the spleen of cadmium-exposed mice compared with those in untreated controls were observed. Treatment of cadmium-exposed mice with DMSA or Sal recovered the spleen weight and hematological parameters to normal control values, decreased cadmium concentration in the blood and spleen, and improved splenic architecture. The results prove that Sal is a potential antidote for treatment of Cd-induced spleen dysfunction.

A rapid cell-based assay for determining poloxamer quality in CHO suspension cell culture.

Poloxamers are water-soluble polymers that are widely used in cell culture bioprocessing to protect cells against shearing forces. Use of poor-quality poloxamers may lead to a drastic reduction in cell growth, viabilities and productivities in cell culture-based manufacturing. In order to evaluate poloxamer quality and promote more consistent performance, a rapid cell membrane adhesion to hydrocarbon assay was developed based on the adhesive properties of cell membranes to selective hydrocarbons. The assay can identify a poor-performing poloxamer characterized by significant drop in viable cell density and percent viability. The assay was verified across multiple good and bad poloxamer lots, and the results were in agreement with established cell growth and high-performance liquid chromatography assays.

MicroRNA-Mediated Health-Promoting Effects of Phytochemicals.

Phytochemicals are known to benefit human health by modulating various cellular processes, including cell proliferation, apoptosis, and inflammation. Due to the potential use of phytochemicals as therapeutic agents against human diseases such as cancer, studies are ongoing to elucidate the molecular mechanisms by which phytochemicals affect cellular functions. It has recently been shown that phytochemicals may regulate the expression of microRNAs (miRNAs). MiRNAs are responsible for the fine-tuning of gene expression by controlling the expression of their target mRNAs in both normal and pathological cells. This review summarizes the recent findings regarding phytochemicals that modulate miRNA expression and promote human health by exerting anticancer, photoprotective, and anti-hepatosteatosis effects. Identifying miRNAs modulated by phytochemicals and understanding the regulatory mechanisms mediated by their target mRNAs will facilitate the efforts to maximize the therapeutic benefits of phytochemicals.

Assessment of epigenetic changes and oxidative DNA damage in rat pups exposed to polychlorinated biphenyls and the protective effect of curcumin in the prenatal period.

Background Polychlorinated biphenyls (PCBs) are persistent organic chemicals that exert neurotoxic and endocrine disrupting effects. The aims of this study were to examine the effects of prenatal Aroclor 1254 (PCBs mixture) exposure on central nervous system tissues DNA and to evaluate the effects of curcumin. Methods Rat pups were assigned to three groups: [Group 1], Aroclor 1254 administrated group; [Group 2], Aroclor 1254 and curcumin administrated group; and [Group 3], control group. Plasma, cerebrum, cerebellum, pons and medulla oblongata tissue homogenates 8-hydroxy-2'-deoxyguanosine [8-(OH)DG] levels and plasma freeT4 levels were determined. Global DNA methylation and hydroxymethylation status were determined in cerebrum, cerebellum, pons and medulla oblongata. To this aim, DNA 5-hydroxymethylcytosine and 5-methylcytosine levels were measured, respectively. Results Mean cerebellum and cerebral cortex 5-hydroxymethylcytosine and 5-methylcytosine levels were higher in the control group than in the experimental groups. Mean plasma, cerebellum and cerebral cortex 8-(OH)DG concentrations were higher in Group 1 than the control group. No statistically significant difference was observed between Group 2 and the control group in terms of cerebellum and cerebral cortex 8-(OH)DG concentrations. Histopathological changes were also observed in the cerebral cortex and cerebellum of rat pups exposed to Aroclor 1254. PCBs exposure changes both DNA methylation and hypomethylation status and induces cerebellar and cerebral cortex DNA damage in the prenatal period. Exogenous curcumin may have protective effect on PCBs-induced DNA damage in cerebellum and cerebral cortex.

Assessment of exogenous melatonin action on mouse liver cells after exposure to soman.

Melatonin is a hormone with many different biological activities and therefore seems to be an important factor reducing the harmful effects caused by toxic organophosphorus compounds. In this study, we attempted to evaluate the protective effect of melatonin on liver cells of mice challenged with chemical warfare agent-soman. The study was conducted at the level of ultrastructural and biochemical changes (analysis of the activity of model lysosomal enzymes and assessment of the level of lipid peroxidation). Significant biochemical and ultrastructural changes were found in the studied mouse hepatocytes after administration of soman alone, and soman in combination with melatonin, and the scope of the disclosed changes was dependent on the time of action of the examined factors. Melatonin has shown protective action, shielding liver cells from toxic effects of soman, which may result from its antioxidant properties and stimulation of the lysosomal compartment, the system coordinating the isolation and removal of cell-threatening processes.

Characterization of Recombinant Phascolosoma esculenta Ferritin as an Efficient Heavy Metal Scavenger.

BACKGROUND: With economic development, the amount of industrial wastewater discharged with heavy metal ions increases, and heavy metal ion pollution in the environment worsens. Currently, this environmental issue has attracted much attention triggering the development and implication of pollutant binding- or degradation-related genes, especially in heavy metal ion detoxification. Additionally, accumulative results have shown that natural ferritin could store multiple toxic metal ions due to its great storage capacity, resulting in heavy metal detoxification in vivo. OBJECTIVE: In this study, the function of recombinant Phascolosoma esculenta ferritin as an efficient heavy metal scavenger was investigated. METHOD: In this study, a recombinant ferritin (rferritin) was purified. The structure and heavy metal chelating capacity were examined via SEM, EDS, AFM and ICP-MS. The protection of rferritin on heavy metal toxicity was identified via cell experiments. RESULTS: The rferritin was expressed by E. coli host. The surface morphology and nanoscale structure of rferritin and human ferritin were changed after different heavy metal treatment, and similar protein aggregates were observed under same heavy metal treatment. ICP-MS analysis revealed the enrichment capacity of rferritin varied among different heavy metals and the cell experiments further confirmed that rferritin could protect the bone marrow mesenchymal stem cells against heavy metal toxicity. CONCLUSION: The rferritin showed an excellent ability to enrich different heavy metals. The adsorption process featured stability, a high yield, simple implementation and low-cost. Thus, the rferritin shows significant potential in the manufacturing of drugs for heavy metal detoxification and environmental remediation.

Assessment of sulforaphane-induced protective mechanisms against cadmium toxicity in human mesenchymal stem cells.

Cd is a hazardous substance and carcinogen that is present in the environment; it is known to cause toxic effects in living organisms. Sulforaphane is a naturally available phytochemical with antioxidant, anti-inflammatory, and anticarcinogenic properties. However, the effects of sulforaphane on Cd toxicity in human mesenchymal stem cells (hMSCs) are unknown. In the present study, we investigated the molecular mechanisms of the effects of sulforaphane on Cd toxicity in hMSCs by using MTT assays, acridine orange/ethidium bromide staining, Hoechst staining, LysoRed staining, assessment of mitochondrial membrane potential, and gene expression analysis. Cd decreased hMSC viability in a dose-dependent manner with an IC50 value of 56.5 µM. However, sulforaphane did not induce any significant reduction in cell viability. Nuclear morphological analysis revealed that Cd induced necrotic cell death. Additionally, Cd caused mitochondrial membrane potential loss in hMSCs. The treatment of Cd-exposed cells with sulforaphane (Cd-sulforaphane co-treatment) resulted in a significant recovery of the cell viability and nuclear morphological changes compared with that of cells treated with Cd only. The gene expression pattern of cells co-treated with Cd-sulforaphane was markedly different from that of Cd-treated cells, owing to the reduction in Cd toxicity. Our results clearly indicated that sulforaphane reduced Cd-induced toxic effects in hMSCs. Overall, the results of our study suggested that sulforaphane-rich vegetables and fruits can help to improve human health through amelioration of the molecular effects of Cd poisoning.

Marine fungal DHICA as a UVB protectant: Assessment under in vitro and in vivo conditions.

The present study explores UVB protective role of a melanin precursor namely DHICA (5,6- Dihydroxyindole-2-carboxylic acid) expressed by the marine imperfect fungus Aspergillus nidulans. In brief, A. nidulans grown in a modified growth medium for the period of 5 days at 25 °C under shaking conditions and the extracellular medium free from fungal biomass used for the extraction of DHICA. The extracted DHICA further exposed to partial purification and subjected to UVB protection studies using HaCaT cells and Balb/c mice independently. DHICA obtained in the present study found soluble in water. Experiments on HaCaT cell compatibility revealed nil cell death up to 500 µM concentration of DHICA. UVB protection studies under in vitro conditions emphasizes DHICA significantly protect HaCaT cells from UVB exposure by quenching the generated ROS, reducing cell apoptosis, maintain the cellular integrity and sequentially down regulating the LPO (Lipid peroxidation) and up-regulating the antioxidant enzyme (SOD (Superoxide Dismutase), Catalase, GPx (Glutathione peroxidase)) respectively. Further, experiments on cell cycle arrest analysis, gelatin zymography, and western blot analysis on COX-2 and TNF-alpha, IHC (Immunohistochemistry) on apoptotic markers (Bax, Bcl2) substantiate the protective role of DHICA. Furthermore, in vivo studies on BALB/c mice carried out and compared with the sunscreen cream with sun protective factor (SPF) of 20. Analysis of skin sections of experimental samples revealed that an appreciable reduction in the epidermal thickness of the skin samples of mice pre-exposed to DHICA followed by UVB exposure compared to UVB exposure alone. RT-PCR results on various inflammatory apoptotic markers also suggested that DHICA has UVB protective potential. The observations made in the present study explore the possible application of DHICA alone as a sun-protective agent for skin care.

Assessment of Titanium Dioxide Nanoparticles (TiO2-NPs) Induced Hepatotoxicity and Ameliorative Effects of Cinnamomum cassia in Sprague-Dawley Rats.

This study assessed the protective effects of Cinnamomum cassia (cinnamon) bark extract in rats exposed to titanium dioxide nanoparticles or titanium dioxide bulk salt. For in vivo evaluation of the ameliorative role of the cinnamon extract, the experimental groups were orally administered with the cinnamon extract at different dose levels (50 or 100 or 150 mg/kg bodyweight) along with the subcutaneous injections of 150 mg/kg bodyweight titanium dioxide nanoparticles or titanium dioxide bulk salt. The extract showed significant ameliorative role on the antioxidant system in response to elevated levels of titanium dioxide nanoparticles or titanium dioxide bulk salt-induced oxidative stress. It aided in the recovery of the antioxidant system as well as protective role in histological damages and some haematological parameters in the rat liver treated with titanium dioxide nanoparticles or titanium dioxide bulk salt.

Assessment of protective potential of Nigella sativa oil against carbendazim- and/or mancozeb-induced hematotoxicity, hepatotoxicity, and genotoxicity.

Nigella sativa oil (NSO) possesses antioxidant activity. However, its protective role against the hazards of fungicides has been poorly studied. Therefore, the present work aimed at determining the ameliorative potential of NSO against hepatotoxicity induced by carbendazim (CBZ) and/or mancozeb (MNZ) in female rats. In the present study, about 120 adult female Sprague-Dawley rats were randomly divided into eight equal groups. One group of animals was kept as a negative control (Gp. 1); groups 2, 3 and 4 orally received CBZ (200 mg/kg body wt) and/or MNZ (300 mg/kg body wt) daily for 2 weeks (positive groups). In order to assess the hepatoprotective potential of NSO, in comparison with NSO-treated rats (Gp. 5), groups 6, 7 and 8 were CBZ- and/or MNZ-exposed groups pre-treated orally with NSO (2 ml/kg body wt) daily for 2 weeks (prophylactic groups). All groups were kept further for 15 days without medications to observe the withdrawal effect. At the end of exposure and withdrawal periods, the body weight of all experimental rats was recorded and blood samples were collected for hematological, clinico-biochemical, and micronucleus assays. The animals were then sacrificed, and the liver and bone marrow were harvested for oxidative stress bioassay, chromosomal aberrations, DNA fragmentation, and histopathological examinations. The results suggested that pre-treatment with NSO remarkably diminished CBZ- and MNZ-induced macrocytic hypochromic anemia, leukocytosis, lymphocytosis, eosinophilia, and neutropenia. Besides, it also minimized the elevated liver enzymes, lipid peroxidation, micronucleus incidence, DNA damage, and chromosomal aberration frequency. Conversely, NSO significantly stimulated the CBZ- and/or MNZ-induced antioxidant system suppression. The NSO also normalized the hepatic structural architecture. As far as withdrawal effect is concerned, there was almost disappearance of the bad effects of these fungicides and the values were close to the normal range especially with the use of NSO. Ultimately, the results revealed that N. sativa oil is an effective hepatoprotective agent due to its genoprotective and free radical scavenging activities.