Neuroimmunopathology in Toxoplasmic Encephalitis

Toxoplasma gondii is a zoonotic protozoan parasite that causes mortality because of significant neuropathology. It is widespread in neonatal infections. Although the neuroimmunopathogenesis of toxoplasmic encephalitis (TE) has been studied for many years, it is still not completely understood, showing the disease’s severity. The urge to write this chapter comes at this stage. The sections covered in this chapter show the pathogenesis that has been established and characterized so far. The involvement of astrocytes and microglia in the development of neuropathology, which begins with tachyzoites crossing the blood-brain barrier during acute infection, has been explored. The molecular mechanism between schizophrenia and TE has been thoroughly proven. Uncovering the molecular pathogenesis of TE is critical for both understanding neuropathology and elucidating the link between neuropsychiatric diseases. Each part covered here is expected to contribute to developing novel therapeutic agents for the treatment and maybe prevention of neuropathology. The pathogenesis of the steady progression of encephalitis has been meticulously revealed. Thus, this chapter will offer significant insight into developing novel treatments for all organisms suffering from this disease

The Protective Properties of the Strawberry (Fragaria ananassa) against Carbon Tetrachloride-Induced Hepatotoxicity in Rats Mediated by Anti-Apoptotic and Upregulation of Antioxidant Genes Expression Effects

The strawberry (Fragaria ananassa) has been extensively used to treat a wide range of ailments in many cultures. The present study was aimed at evaluating the hepatoprotective effect of strawberry juice on experimentally induced liver injury in rats. To this end, rats were introperitoneally injected with carbon tetrachloride (CCl4) with or without strawberry juice supplementation for 12 weeks and the hepatoprotective effect of strawberry was assessed by measuring serum liver enzyme markers, hepatic tissue redox status and apoptotic markers with various techniques including biochemistry, ELISA, quantitative PCR assays and histochemistry. The hepatoprotective effect of the strawberry was evident by preventing CCl4-induced increase in liver enzymes levels. Determination of oxidative balance showed that strawberry treatment significantly blunted CCl4-induced increase in oxidative stress markers and decrease in enzymatic and non-enzymatic molecules in hepatic tissue. Furthermore, strawberry supplementation enhanced the anti-apoptotic protein, Bcl-2, and restrained the pro-apoptotic proteins Bax and caspase-3 with a marked reduction in collagen areas in hepatic tissue. These findings demonstrated that strawberry (Fragaria ananassa) juice possessed antioxidant, anti-apoptotic and anti-fibrotic properties, probably mediated by the presence of polyphenols and flavonoids compounds

Naturally Occurring Triggers that Induce Apoptosis-Like Programmed Cell Death in Plasmodium berghei Ookinetes

Several protozoan parasites have been shown to undergo a form of programmed cell death that exhibits morphological features associated with metazoan apoptosis. These include the rodent malaria parasite, Plasmodium berghei. Malaria zygotes develop in the mosquito midgut lumen, forming motile ookinetes. Up to 50% of these exhibit phenotypic markers of apoptosis; as do those grown in culture. We hypothesised that naturally occurring signals induce many ookinetes to undergo apoptosis before midgut traversal. To determine whether nitric oxide and reactive oxygen species act as such triggers, ookinetes were cultured with donors of these molecules. Exposure to the nitric oxide donor SNP induced a significant increase in ookinetes with condensed nuclear chromatin, activated caspase-like molecules and translocation of phosphatidylserine that was dose and time related. Results from an assay that detects the potential-dependent accumulation of aggregates of JC-1 in mitochondria suggested that nitric oxide does not operate via loss of mitochondrial membrane potential. L-DOPA (reactive oxygen species donor) also caused apoptosis in a dose and time dependent manner. Removal of white blood cells significantly decreased ookinetes exhibiting a marker of apoptosis in vitro. Inhibition of the activity of nitric oxide synthase in the mosquito midgut epithelium using L-NAME significantly decreased the proportion of apoptotic ookinetes and increased the number of oocysts that developed. Introduction of a nitric oxide donor into the blood meal had no effect on mosquito longevity but did reduce prevalence and intensity of infection. Thus, nitric oxide and reactive oxygen species are triggers of apoptosis in Plasmodium ookinetes. They occur naturally in the mosquito midgut lumen, sourced from infected blood and mosquito tissue. Up regulation of mosquito nitric oxide synthase activity has potential as a transmission blocking strategy

Antischistosomal and anti-inflammatory activity of garlic and allicin compared with that of praziquantel in vivo

Abstract Background Schistosomiasis is an acute and chronic zoonotic parasitic disease caused by trematode worms. The host inflammatory response to schistosome eggs leads to perioval granulomata formation, mainly in the liver and intestine. This study investigated the potential antischistosomal and anti-inflammatory activity of both garlic extract and allicin on liver fibrotic markers in BALB/c mice with schistosomiasis (S. mansoni infection) compared with that of the commonly used drug, praziquantel (PZQ). Methods In this study, 140 female BALB/c mice (7-weeks old) were divided into seven groups with 20 mice each. Six groups were infected with S. mansoni cercariae and treated with garlic, allicin, or PZQ. The seventh group was the negative control. Twenty-four hours after the final treatment, the mice were euthanised and perfused for worm recovery. The liver and intestines were harvested for parasitological and histological assessment and to analyse the proinflammatory cytokine mRNA expression. Results Prophylactic administration of garlic and allicin to the infected mice significantly reduced the worm burden. Serum concentrations of liver fibrosis markers and proinflammatory cytokines were also reduced. PZQ was the most efficacious for reduction in the number of worms. These results are similar to those normally obtained using PZQ. Conclusions Crushed garlic homogenate and allicin are potential complementary treatments that may be used with PZQ

ADAMTS-13 and HMGB1-induced oxidative stress in Taenia multiceps-infected animals

This study investigated the cytotoxic effects of oxidative stress (OS), high mobility group box 1 (HMGB1), ADAMTS (A disintegrin and metalloproteinase with thrombospondin motifs), and neuropathology associated with coenurus cerebralis (Taenia multiceps). ADAMTS-13, HMGB1, glutathione reductase (GR), copper/zinc superoxide dismutase (Cu/Zn SOD), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) expression levels were studied. The study found that ADAMTS-13 (P &lt; 0.005), HMGB1 (P &lt; 0.005), GR (P &lt; 0.005), Cu/Zn SOD (P &lt; 0.005), and 8-OHdG (P &lt; 0.005) levels were significantly higher in&nbsp;T. multiceps&nbsp;(c. cerebralis)-infected animals compared to healthy control animals. This study's most important finding was that HMGB1 up-regulation in neurons, endothelial cells, and glial cells can directly cause brain parenchymal destruction and that HMGB1-mediated oxidative stress plays a crucial role in the neuropathogenesis of coenurosis. The results also showed that increased levels of ADAMTS-13 may play a pivotal role in regulating and protecting the blood–brain barrier integrity and neuroprotection. These findings also suggest that ADAMTS-13 and HMGB1 compete in the prevention or formation of microthrombi, which was regarded as a remarkable finding. ADAMTS-13 and HMGB1 are valuable biomarkers for disease risk assessment, estimating host neuropathy following&nbsp;T. multiceps&nbsp;(c. cerebralis) exposure, and providing a new therapeutic target. This is the first study to show that HMGB1 and ADAMTS-13 are expressed in reactive cells and are associated with neuroimmunopathology in coenurosis.</p

Protective effects of pomegranate (Punica granatum) juice on testes against carbon tetrachloride intoxication in rats

BACKGROUND: Pomegranate fruit has been extensively used as a natural medicine in many cultures. The present study was aimed at evaluating the protective effects of pomegranate (Punica granatum) juice against carbon tetrachloride (CCl(4))-induced oxidative stress and testes injury in adult Wistar rats. METHODS: Twenty eight Wistar albino male rats were divided equally into 4 groups for the assessment of protective potential of pomegranate juice. Rats of group I (control) received only vehicles and had free access to food and water. Rats of groups II and IV were treated with CCl(4) (2 ml/kg bwt) via the intraperitoneal route once a week for ten weeks. The pomegranate juice was supplemented via drinking water 2 weeks before and concurrent with CCl(4) treatment to group IV. Group III was supplemented with pomegranate juice for twelve weeks. The protective effects of pomegranate on serum sex hormones, oxidative markers, activities of antioxidant enzymes and histopathology of testes were determined in CCl(4)-induced reproductive toxicity in rats. RESULTS: Pomegranate juice showed significant elevation in testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) those depleted by the injection of CCl(4). Activity levels of endogenous testesticular antioxidant enzymes; superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) and glutathione (GSH) contents were increased while lipid peroxidation (LPO) and nitric oxide (NO) were decreased with pomegranate juice. Moreover, degeneration of germ and Leydig cells along with deformities in spermatogenesis induced after CCl(4) injections were restored with the treatment of pomegranate juice. CONCLUSION: The results clearly demonstrated that pomegranate juice augments the antioxidant defense mechanism against carbon tetrachloride-induced reproductive toxicity and provides evidence that it may have a therapeutic role in free radical mediated diseases

Anti-Leishmanial Activity (<i>In Vitro</i> and <i>In Vivo</i>) of Allicin and Allicin Cream Using <i>Leishmania major</i> (Sub-strain Zymowme LON4) and Balb/c Mice

<div><p>Background</p><p><i>Leishmania</i> is a unicellular protozoan parasite that produces several human diseases, ranging from localized self-healing cutaneous lesions to deadly visceral infections.</p><p>Objective</p><p>The effect of allicin on the growth of <i>Leishmania major (L</i>. <i>major)</i> promastigotes was evaluated under <i>in vitro</i> conditions. Moreover, the efficacy of a topical allicin cream was examined in BALB/c (Bagg <a href="https://en.wikipedia.org/wiki/Albino" target="_blank">albino</a>, laboratory-bred strain of the <a href="https://en.wikipedia.org/wiki/House_Mouse" target="_blank">House Mouse</a>) mice with cutaneous leishmanial lesions compared to the currently used drug, sodiumstibogluconate (pentostam).</p><p>Methods</p><p>Cytotoxiciy and promastigote proliferation were measured. Different concentrations (50, 100, 150, and 200 μM) of liquid allicin were tested on <i>L</i>. <i>major</i> promastigotes twice: after 24 and 48 hours using an MTT colorimetric assay. In the <i>in vivo</i> condition, the efficacies of allicin cream and liquid allicin at two concentrations (0.15 μM/mouse and 0.30 μM/mouse) were evaluated. Serum factors of the control and treated groups were tested to evaluate the toxic effects of allicin on the liver and kidney.</p><p>Results</p><p>Allicin at a concentration of 50 μM inhibited the growth of <i>Leishmania</i> promastigotes. Topical application of allicin cream reduced lesion sizes in mice. No significant differences in biochemical analysis were observed between the control and treated groups.</p><p>Conclusions</p><p>Allicin has antileishmanial effects under <i>in vitro</i> and <i>in vivo</i> conditions and may be used in clinical applications.</p></div

Lesion Size (mm) on Different days Post Infection and Treatment.

<p>Lesion Size (mm) on Different days Post Infection and Treatment.</p

Agarose Gel (1.5%) Electrophoresis of PCR Amplification for the Identification of <i>L</i>. <i>Major</i>.

<p>M: 1000-bp DNA ladder marker, Lane 1: treatment with pentostam (Pe), Lane 2: prophylaxis with allicin (Pre-a). Lane 3: treatment with liquid oral allicin (OA). Lane 4: allicin cream (AC). Lane 5: <i>L</i>. <i>major</i> (+ C). Lane 6: negative control (- C).</p