Viral and bacterial infections are often associated with deficiencies in macronutrients and micronutrients, including the essential trace element selenium. In selenium deficiency, benign strains of Coxsackie and influenza viruses can mutate to highly pathogenic strains. Dietary supplementation to provide adequate or supranutritional selenium supply has been proposed to confer health benefits for patients suffering from some viral diseases, most notably with respect to HIV and influenza A virus (IAV) infections. In addition, selenium-containing multimicronutrient supplements improved several clinical and lifestyle variables in patients coinfected with HIV and Mycobacterium tuberculosis. Selenium status may affect the function of cells of both adaptive and innate immunity. Supranutritional selenium promotes proliferation and favors differentiation of naive CD4-positive T lymphocytes toward T helper 1 cells, thus supporting the acute cellular immune response, whereas excessive activation of the immune system and ensuing host tissue damage are counteracted through directing macrophages toward the M2 phenotype. This review provides an up-to-date overview on selenium in infectious diseases caused by viruses (e.g., HIV, IAV, hepatitis C virus, poliovirus, West Nile virus) and bacteria (e.g., M. tuberculosis, Helicobacter pylori). Data from epidemiologic studies and intervention trials, with selenium alone or in combination with other micronutrients, and animal experiments are discussed against the background of dietary selenium requirements to alter immune functions.

Background: To date all efforts to develop a malaria vaccine have failed, reflecting the still fragmentary knowledge about protective mechanisms against malaria. In order to evaluate if vaccination changes responses of the anti-malaria effectors spleen and liver to blood stage malaria, BALB/c mice succumbing to infection with Plasmodium chabaudi were compared to those surviving after vaccination.

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The current study was designed to investigate the beneficial role of diosmin, a biologically active flavonoid, against methotrexate- (MTX-) induced hepatic, renal, and cardiac injuries in mice. Male Swiss albino mice received a single intraperitoneal injection of MTX (at 20 mg/kg, body weight) either alone or in combination with oral diosmin (at 50 or 100 mg/kg body weight, for 10 days). Serum was used to evaluate tissue injury markers, while hepatic, renal, and cardiac tissue samples were obtained for determination of antioxidant activity as well as histopathological examination. Diosmin treatment ameliorated the MTX-induced elevation of serum alkaline phosphatase, aminotransferases, urea, creatinine, lactate dehydrogenase, and creatine kinases as well as plasma proinflammatory cytokines (interleukin-1-beta, interleukin-6, and tumor necrosis factor-alpha). Additionally, both diosmin doses significantly reduced tissue levels of malondialdehyde and nitric oxide and increased those of glutathione, glutathione peroxidase, glutathione reductase, glutathione S-transferase, superoxide dismutase, and catalase, compared to the MTX-intoxicated group. Histopathological examination showed that diosmin significantly minimized the MTX-induced histological alterations and nearly restored the normal architecture of hepatic, renal, and cardiac tissues. Based on these findings, diosmin may be a promising agent for protection against MTX-induced cytotoxicity in patients with cancer and autoimmune diseases.

Coccidiosis and helminthosis in poultry are responsible for worldwide economic losses. The methanolic extract of Punica granatum (pomegranate) peel was used in vivo for its pharmacological, antioxidant and anti-coccidial properties and in vitro for its anthelmintic activity. For the in vivo study, four groups of mice were investigated. The first group was inoculated only with sterile saline and served as the control group. The second group was treated by oral gavage with pomegranate extract (300 mg/kg) daily for 5 days. The third and fourth groups were infected with 10(3) sporulated oocysts of Eimeria papillata. The fourth group was also treated once daily with pomegranate peel extract for 5 days. For the in vitro study, the anthelmintic effect of pomegranate peel extract was observed on live adult Allolobophora caliginosa. Paraffin sections from jejunum as well as jejunal homogenate were prepared for the histopathological and biochemical investigations, respectively. The data showed that mice infected with E. papillata revealed an output of approximately 2.9 × 10(5) oocysts per gram faeces on day 5 p.i. This output is significantly decreased to 50 % in pomegranate-treated mice. Infection with E. papillata induced marked histopathological alterations in jejunum in the form of inflammation, vacuolation of the epithelium and destruction of some villi. In addition, pomegranate extract caused a great diminish in body weight loss of infected mice. Moreover, the number of goblet cells stained with Alcian blue within the infected villi was significantly increased by about 26 % after pomegranate treatment. In addition, Pomegranate significantly lowered the increased number of apoptotic cells due to E. papillata infection by about 36 %. The results showed that E. papillata enhanced hydrogen peroxide, lipid peroxidation and nitric oxide production with concomitant reduction in glutathione. Pomegranate induced marked improvements in all of the studied parameters as well as the histopathological features of jejunum. In addition, pomegranate was able to exert a significant anthelmintic effect on live adult A. caliginosa worms in terms of the paralysis and death of the worms at different concentrations (100, 200 and 300 mg/ml). The study revealed that pomegranate as a natural product has protective effects against E. papillata-induced coccidiosis as well as it possesses an anthelmintic activity.

Testosterone induces a lethal outcome in otherwise self-healing blood-stage malaria caused by Plasmodium chabaudi. Here, we examine possible testosterone effects on the antimalaria effectors spleen and liver in female C57BL/6 mice. Self-healing malaria activates gating mechanisms in the spleen and liver that lead to a dramatic reduction in trapping activity, as measured by quantifying the uptake of 3-m-diameter fluorescent polystyrol particles. However, testosterone delays malaria-induced closing of the liver, but not the spleen. Coincidently, testosterone causes an ϳ3-to 28-fold depression of the mRNA levels of nine malaria-responsive genes, out of 299 genes tested, only in the liver and not in the spleen, as shown by cDNA arrays and Northern blotting. Among these are the genes encoding plasminogen activator inhibitor (PAI1) and hydroxysteroid sulfotransferase (STA2). STA2, which detoxifies bile acids, is suppressed 10-fold by malaria and an additional 28-fold by testosterone, suggesting a severe perturbation of bile acid metabolism. PAI1 is protective against malaria, since disruption of the PAI1 gene results in partial loss of the ability to control the course of P. chabaudi infections. Collectively, our data indicate that the liver rather than the spleen is a major target organ for testosteronemediated suppression of resistance against blood-stage malaria.

Abstract:We investigated the protective and antioxidative effects of selenium nanoparticles (SeNPs) in streptozotocin STZ-induced diabetic rats. STZ-diabetic rats were exposed daily to treatments with SeNPs and/or insulin and then the effect of these treatments on the parameters correlated to oxidative damage of the rat testes were assessed. Biochemical analysis revealed that SeNPs are able to ameliorate the reduction in the serum testosterone caused by STZ-induced diabetes. Furthermore, SeNPs could significantly decrease testicular tissue oxidative stress markers, namely lipid peroxidation and nitric oxide. In contrast, treatment of the STZ-diabetic rats with SeNPs increased the glutathione content and antioxidant enzyme activities in testicular tissues. Moreover, microscopic analysis proved that SeNPs are able to prevent histological damage in the testes of STZ-diabetic rats. Molecular analysis revealed that the mRNA level of Bcl-2 (B-cell lymphoma 2) is significantly upregulated. On the contrary, the mRNA level of Bax (Bcl-2 Associated X Protein) was significantly downregulated. Furthermore, treatment of STZ-diabetic rats with SeNPs led to an elevation in the expression of PCNA (Proliferating Cell Nuclear Antigen Gene). Interestingly, the insulin treatment also exhibited a significant improvement in the testicular function in STZ-diabetic rats. Collectively, our results demonstrated the possible effects of SeNPs in attenuating diabetes-induced oxidative damage, in particular in testicular tissue.

Eimeriosis, a widespread infectious disease of livestock, is caused by coccidian protozoans of the genus Eimeria. These obligate intracellular parasites strike the digestive tract of their hosts and give rise to enormous economic losses, particularly in poultry, ruminants including cattle, and rabbit farming. Vaccination, though a rational prophylactic measure, has not yet been as successful as initially thought. Numerous broad-spectrum anti-coccidial drugs are currently in use for treatment and prophylactic control of eimeriosis. However, increasing concerns about parasite resistance, consumer health, and environmental safety of the commercial drugs warrant efforts to search for novel agents with anti-Eimeria activity. This review summarizes current approaches to prevent and treat eimeriosis such as vaccination and commercial drugs, as well as recent attempts to use dietary antioxidants as novel anti-Eimeria agents. In particular, the trace elements selenium and zinc, the vitamins A and E, and natural products extracted from garlic, barberry, pomegranate, sweet wormwood, and other plants are discussed. Several of these novel anti-Eimeria agents exhibit a protective role against oxidative stress that occurs not only in the intestine of Eimeria-infected animals, but also in their non-parasitized tissues, in particular, in the first-pass organ liver. Currently, it appears to be promising to identify safe combinations of low-cost natural products with high anti-Eimeria efficacy for a potential use as feed supplementation in animal farming.