Antimicrobial and anti-viral effects of selenium nanoparticles and selenoprotein based strategies: COVID-19 and beyond.

Deficiency of selenium (Se) has been described in a significant number of COVID-19 patients having a higher incidence of mortality, which makes it a pertinent issue to be addressed clinically for effective management of the COVID-19 pandemic. Se nanoparticles (SeNPs) provide a unique option for managing the havoc caused by the COVID-19 pandemic. SeNPs possess promising anti-inflammatory and anti-fibrotic effects by virtue of their nuclear factor kappa-light-chain-stimulator of activated B cells (NFκB), mitogen-activated protein kinase (MAPKs), and transforming growth factor-beta (TGF-ß) modulatory activity. In addition, SeNPs possess remarkable immunomodulatory effects, making them a suitable option for supplementation with a much lower risk of toxicity compared to their elemental counterpart. Further, SeNPs have been shown to curtail viral and microbial infections, thus, making it a novel means to halt viral growth. In addition, it can be administered in the form of aerosol spray, direct injection, or infused thin-film transdermal patches to reduce the spread of this highly contagious viral infection. Moreover, a considerable decrease in the expression of selenoprotein along with enhanced expression of IL-6 in COVID-19 suggests a potential association among selenoprotein expression and COVID-19. In this review, we highlight the unique antimicrobial and antiviral properties of SeNPs and the immunomodulatory potential of selenoproteins. We provide the rationale behind their potentially interesting properties and further exploration in the context of microbial and viral infections. Further, the importance of selenoproteins and their role in maintaining a successful immune response along with their association to Se status is summarized.

MiADMSA ameliorate arsenic induced urinary bladder carcinogenesis in vivo and in vitro.

BACKGROUND AND PURPOSE: Arsenicosis is a major threat to public health and is a major cause of the development of urinary bladder cancer. Oxidative/ nitrosative stress is one of the key factors for these effects but the involvement of other associated factors is less known. There is a lack of data for the efficacy of chelator against urinary bladder carcinogenesis. The present study demonstrates the early signs of arsenic exposed urinary bladder carcinogenesis and its attenuation by Monoisoamyl dimercaptosuccinic acid (MiADMSA). METHODS: Male rats were exposed to 50 ppm of sodium arsenite and dimethylarsinic acid (DMA) via drinking water for 18 weeks and treated with MiADMSA (50 mg/kg, orally once daily for 5 days) for 3 weeks with a gap one week between the two courses of treatments. We compared in vivo data with in vitro by co-exposing 100 nM of sodium arsenite and DMA to rat (NBT-II) as well as human transitional epithelial carcinoma (T-24) cells with 100 nM of MiADMSA. RESULTS: The data showed that sodium arsenite and DMA exposure significantly increased the tissue arsenic contents, ROS, TBARS levels, catalase, SOD activities and significantly decreased GSH level which might be responsible for an increased 8-OHdG level. These changes might have increased pro-oncogenic biomarkers like MMP-9 and survivin in serum, bladder tissues, NBT-II, and T-24 cells. High cell migration and clonogenic potential in NBT-II and T-24 cells exposed to arsenic suggest pronounced carcinogenic potential. Significant recovery in these biomarkers was noted on treatment with MiADMSA. CONCLUSION: Early signs of urinary bladder carcinogenesis were observed in arsenic and DMA exposed rats which were linked to metal accumulation, oxidative/ nitrosative stress, 8-OHdG, MMP-9 and survivin which were reduced by MiADMSA possibly via its efficient chelation abilities in vivo and in vitro.

Gallic acid and MiADMSA reversed arsenic induced oxidative/nitrosative damage in rat red blood cells.

Arsenic (As) is naturally occurring toxic metalloid which is considered as a serious environmental and health concern. Red blood cells are the prime target for any toxicants as their population is higher in systemic circulation. High prevalence of anaemia too has been reported from arsenic contaminated area, suggesting possible linkage between arsenic and the damaging effects on RBCs. The exact mechanism for these effects is still not clear, however, oxidative/nitrosative stress might be one of the causative factors to play a key role. The present study was planned to evaluate the protective effects of a metal chelator, MiADMSA either alone or in combination with a natural antioxidant (gallic acid) for the reversal of arsenic induced oxidative damage in red blood cells. We collected rat RBCs and cultured them in appropriate medium. They were incubated with MiADMSA and gallic acid and then treated with sodium arsenite at 37 °C. Hemolysates were prepared and assayed for various biochemical parameters such as oxidative/nitrosative variables, osmotic fragility, acetylcholinesterase activity, and cellular metal accumulation. We found there was reversibility of oxidative/nitrosative stress variables, elevated cellular antioxidant power, and decreased osmotic fragility of red blood cells both in MiADMSA alone as well as in combination with gallic acid treated group compared with arsenic treated group. In conclusion, MiADMSA efficiently participated in the reversal of arsenic induced oxidative/nitrosative damage in red blood cells where as Gallic acid improved its reversal when given in combination with MiADMSA.

Chronic copper exposure elicit neurotoxic responses in rat brain: Assessment of 8-hydroxy-2-deoxyguanosine activity, oxidative stress and neurobehavioral parameters.

Copper (Cu), one of the essential transition metal acts as a prosthetic group for variety of proteins and metalloenzymes. However, it may be hazardous when administered in excess. Copper induced memory impairment and progression of neurodegenerative diseases have not yet been fully elucidated. The aim of the present study was to investigate the effect of exposure to copper sulphate (10mg/kg and 20mg/kg body weight, daily for 16 weeks) on brain copper concentration, few biochemical parameters indicative of oxidative stress and on different neurobehavioral functions in male Sprague Dawley rats. Copper-administered animals showed significant increase in brain copper concentration and a depleted Ceruloplasmin level. Different neurobehavioral studies revealed impaired memory and motor coordination in copper exposed rat. Spontaneous locomotors activity and depression symptoms were also noted in copper intoxicated rats. 8-hydroxy-2' -deoxyguanosine (8-OHdG) level, one of the predominant forms of free radical-induced oxidative lesions, and has been widely used as a biomarker for oxidative stress, increased in copper treated group. Copper induced oxidative stress in the brain was also evident from the increased lipid per oxidation (LPO) and nitrite level, depletion of reduced glutathione (GSH), and reduced activities of the antioxidant enzymes such as superoxide dismutase (SOD), and catalase. The present study thus suggests a significant correlation between copper induced oxidative stress and changes in neurobehavioral function in rats. The changes were more pronounced in animals exposed to a higher dose of copper (20mg/kg) than the lower dose.