Oxidative stress (OS) plays an essential role in the pathogenesis of common neurodegenerative diseases. We have previously shown that Toxoplasma gondii (T. gondii) induces high nitric oxide (NO) ...production, glial activation, and apoptosis that altogether cause severe neuropathology in toxoplasma encephalitis (TE). The objective of this study was to investigate the cytotoxic effect of OS and to identify a correlation between the causes of T. gondii induced neuropathology. Expression levels of glutathione reductase (GR), Cu/Zn superoxide dismutase (SOD1), neuron specific enolase (NSE), and 8-hydroxy-2’-deoxyguanosine (8-OHdG) were investigated. Results of the study revealed that the levels of GR (P <0.005) and NSE (P <0.001) expression in the brain tissue markedly increased while SOD1 activity decreased (P <0.001) in the infected group compared to the non-infected group. In addition, intense staining for 8-OHdG (P <0.05) was observed both in the nucleus and the cytoplasm of neurons and glial cells that underwent OS. These results were reasonable to suggest that T. gondii-mediated OS might play a pivotal role and a different type of role in the mechanism of neurodegeneration/neuropathology in the process of TE. The results also clearly indicated that increased levels of NO and apoptosis might contribute to OS-related pathogenesis of TE. As a result, OS and expression of NSE might give an idea of the disease progress and may have a critical diagnostic significance for patients with T. gondii infection.
The neurotropic pathogen Toxoplasma gondii infects about one-third of the human population. Both acute and chronic (latent or life-long) forms of toxoplasmosis are associated with specific neurologic ...and neuropsychiatric symptoms. In the present study, swiss albino mice were inoculated intraperitoneally with 15–20 tissue cysts of the ME-49 strain of Toxoplasma gondii. The brain samples were collected on the days 10, 20, and 30 for determining the histopathological scores and the number of cysts. Furthermore, a real-time quantitative polymerase chain reaction (RT-PCR) was conducted to find out the gene expression levels of the serotonin 2A receptor (5-HTR2A), serotonin 2C receptor (5-HTR2C), serotonin 6 receptor (5-HTR6), serotonin 7 receptor (5-HTR7), and interleukin-6. The results were compared to the histopathological findings of encephalitic toxoplasmosis. The expression levels were observed to increase for all receptors; however at different time points of infection. This experimental model demonstrates that the expression of serotonin receptors was induced in Toxoplasma gondii infections, displaying unique findings for each of the individual receptors.
Neuroscience; Immunology; Inflammation; Immune response; Pathology; Parasitology; Nervous system; Interleukin 6; Serotonin receptors; Toxoplasma gondii; Encephalitic toxoplasmosis
•IL-10 macrophage immunopositivity shows the elimination of the parasite is insufficient.•Macrophages immunopositive for iNOS is an indication that the host immune response is making an effort to ...eliminate the parasite.•One of the immunological mechanisms involved in cystic echinococcosis is the balance of the Th1 and Th2 response and the macrophage types involved in these responses.
Cystic echinococcosis is a zoonotic parasitic disease caused by Echinococcus granulosus. The main hosts in the life cycle of this parasite are dogs and other carnivores; The intermediate hosts are human, sheep, goat, cattle, pig, buffalo, horse and camel. The parasite damages the tissue by forming lesions in the form of fluid-filled cysts in the liver. These lesions are bounded by a layer of local inflammatory cells formed by the host. In the layer formed by this inflammatory response, there are lymphocytes, neutrophils and eosinophil leukocytes, including macrophages. Samples taken from sheep with hydatid cysts in their livers were followed for pathological analysis, and then histopathological and immunohistochemical examinations were performed. After histopathological examinations, the types of macrophages involved in the local immune response against cysts in the liver were determined by immunohistochemical methods using anti-INOS and anti-IL-10 antibodies. INOS and IL-10 immunopositivity were detected in all samples. Statistically, no significant difference was observed between these immunopositivity. This showed that both macrophage types are involved in the local immune response to hydatid cyst, and that Th1 and Th2 immune response stimulation continues together. It was concluded that in future studies that will be planned and experimentally, it will be possible to reveal more clearly how these macrophage types take part in the local immune response.
Toxoplasma gondii (T. gondii) is a protozoan parasite with the potential of causing severe encephalitis among immunocompromised humans and animals. Our previous study showed that T. gondii induces ...high nitric oxide (NO) production, high glial activation (GFAP) and neurofilament expressions, leading to severe neurodegeneration in toxoplasma encephalitis (TE) in the central nervous system (CNS). The aim of this experimental study was to investigate ADAMTS‐13 expression and apoptosis in CNS and to identify whether they have any correlation with toxoplasmosis neuropathology and neurodegeneration. Mice were infected with ME49 strain T. gondii and the levels of ADAMTS‐13, caspase 3, caspase 8, caspase 9, TNFR1 and Bcl‐xL expressions were examined in brain tissues by immunohistochemistry, during the development and establishment of chronic infections at 10, 30 and 60 days post‐infection. Results of the study revealed that the levels of ADAMTS‐13 (P < 0.005), caspase 3 (P < 0.05), caspase 8 (P < 0.05), caspase 9 (P < 0.005) and TNFR1 (P < 0.05) expressions in the brain markedly increased while Bcl‐xL expression decreased (P < 0.005). The most prominent finding from our study was that 10, 30 and 60 days post‐infection ADAMTS‐13 increased significantly and this may play an important role in the regulation and protection of the blood‐brain barrier integrity and CNS microenvironment in TE. These results also suggest that T. gondii‐mediated apoptosis might play a pivotal role and a different type of role in the mechanism of neurodegeneration and neuropathology in the process of TE. Furthermore, expression of ADAMTS‐13 might give an idea of the progress and is critical for diagnosis of this disease. To the best of the authors' knowledge, this is the first report on ADAMTS‐13 expression in the CNS of T. gondii‐infected mice.
Toxoplasma gondii
is a protozoon parasite which causes toxoplasmosis both in human and warm-blooded animals. Toxoplasmosis is a worldwide disease and largely threats human and animal health ...consequently causing economic losses. Also, it affects the visceral organs in different severity degrees according to the strain of parasite and the host. In this study, experimental toxoplasmosis was performed via intra-peritoneal route in 12 gerbils by administrating 5.00 × 10
3
tachyzoites of
T. gondii
RH strain. The gerbils were sacrificed 7 days after inoculation. All systemic organs were obtained via necropsy and examined by immunohistochemical and histopathological methods. Lesions infected with
T. gondii
mostly observed in the serosa of abdominal cavity organs including stomach, liver, spleen, intestines, and kidneys. The lesions were most severe in liver. The parasite showed an affinity for the hepatic tissue. To our knowledge, this is the first experimental study of acute
T. gondii
infection in gerbil evaluating macroscopic, microscopic and immunohistochemical findings. It is concluded that Mongolian gerbils can be used as experimental animals to investigate toxoplasmosis. Also, these animals are very suitable hosts to study liver pathology and pathobiology of
T. gondii
-related hepatitis.
Acute Toxoplasma gondii infections can influence the liver as well as other organs. Many cytokines and proteins play a role in the acute response against infection. Tumor necrosis factor alpha (TNF ...alpha) is a cytokine that plays a key function in stimulating hepatocytes to produce acute phase proteins. In this study, we investigated TNF alpha levels associated with the levels of macroglobulin, haptoglobin, hemopexin, C-reactive protein (CRP), albumin, serum amyloid alpha protein (SAA), and clusterin, which are acute phase proteins, in serum of mice with T. gondii infection. In the experiment, a total of 24 mice were used; 6 mice constituted the control group and 18 mice were infected with the RH strain. On the 2nd, 4th, and 6th days following the infection, 6 animals were euthanized, and their serums were collected. Compared to the control group, we observed a statistically significant decrease in albumin concentration in the group with T. gondii infection on the 6th day. Also, this group displayed a statistically significant, gradual increase in clusterin levels on the 2nd and 6th days, C-reactive protein levels on the 4th day, haptoglobin levels on the 2nd and 4th days, hemopexin levels on the 2nd day, serum amyloid A levels on the 2nd, 4th, and 6th days, and TNF-α levels on the 2nd, 4th, and 6th days (p < 0.05). TNF-α was strongly positively correlated with CRP, SAA, and clusterin, moderately positively correlated with hemopexin, and strongly negatively correlated with albumin. The increase in CRP, SAA, clusterin, and hemopexin levels on the 2nd day after infection, in parallel with the increase in TNF-α levels, indicates that these proteins can be considered as major acute phase proteins in acute T. gondii infection in mice. The data obtained here may be helpful for the diagnosis of T. gondii infection and for monitoring treatments.
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•Acute phase response is required for the defense of the Toxoplasma gondii infection.•TNF alpha levels associated with the levels of Macroglobulin, Haptoglobin, Hemopexin, CRP, Albumin, SAA, Clusterin.•Observing the acute phase proteins levels may be guiding for the diagnosis of toxoplasmosis and monitoring the treatments.
Hydatid cysts formed by the metacestodes of
Echinococcus granulosus
. Cattle suffering from hydatid cyst shows fluid-filled structures, especially in liver. These parasite-induced cysts localized by ...forming fibrous capsules in the liver. Fibrogenesis is the host immune response in the liver against these parasites. Hepatic stellate cells (HSCs) are localized perisinusoidal space also known as vitamin A-storing cells, characterize the important fibrogenic cell type. In this study, livers from 15 animals with hydatid cyst and 8 healthy animals were used. Hematoxylin and Eosin, masson trichrome staining were performed on the prepared liver sections. Microscopically, cysts were bordered eosinophilic necrotic debris blended with degenerate neutrophils, macrophages, eosinophils, lymphocytes, plasma cells and multinucleated giant cells, which extend into the adjacent fibrous connective tissue. In Masson trichrome staining, the fibrous connective tissue was observed surrounding of hydatid cyst. Glial fibrillary acidic protein (GFAP), collagen I, GFAP/collagen I, positive cells were investigated using either indirect single- or double-labeling immunohistochemical staining. The results indicated that anti-GFAP-positive staining was seen in areas including fibrous tissue just under the foreign body giant cells surrounding the cyst wall. In double immunohistochemical staining, it was observed that HSCs labeled with anti-GFAP antibody in the fibrous connective tissue also labeled anti-collagen I antibody. This study shows that HSCs may responsible for synthesis the collagen I in the development of parasitic fibrosis in cystic echinococcosis in the liver of cattle.
Toxoplasmosis is a disease caused by the protozoan
, which occurs worldwide in mammals and birds. Brain is the primary target organ because
is a ubiquitous intracellular parasite that causes most ...frequently life-threatening encephalitis in immunocompromised patients. Relation of tissue cysts number, histopathology score and acute phase proteins were investigated. In this study, 36 mice are infected with Me49 strain of
The control group has 6 healthy mice. After inoculation of
, at 10., 15., 20., 30., 45., 60. days, 6 each mice euthanized after collection of blood samples. Hemopexin, haptoglobulin, macroglobulin, serum amyloid A and clusterin levels are determined by ELISA. Then, brain tissues were investigated histopathologically and lesions were scored. The average cyst numbers were determined by counting three samples (25 μl each) of each brain homogenate under light microscopy. Inflammatory reaction was observed on day 10 days after inoculation (d.a.i.) The lesions were characterized by perivascular mononuclear cell infiltration, focal mononuclear cell infiltration in the meninges, and glial proliferation. Tissue cysts were observed in all
-infected groups. The highest lesion score was observed at 60 d.a.i. And the most tissue cyst number were on day 30. d.a.i. Serum levels of hemopexin, haptoglobulin, macroglobulin, serum amyloid A and clusterin were significantly higher than the control group on day 10-20., 10., 10-30., 10.,10-45 d.a.i., respectively. High level of acute phase proteins in mice on certain days infected with
was exhibited a relationship between brain lesions and tissue cysts.
•Fluoride is a common environmental pollutant.•Fluoride easily cross the cell membranes and enter soft tissues.•Fluoride causes oxidative stress.•Resveratrol reduces the adverse effects of oxidative ...stress.•Resveratrol exhibits a neuroprotective and hepatoprotective effects.
Protective effect of resveratrol on sodium fluoride-induced oxidative stress, hepatotoxicity and neurotoxicity were studied in rats. A total of 28 Wistar albino male rats were used. Four study groups were randomly formed with seven animals in each. The groups were treated for 21days with distilled water (control group), with water containing 100ppm fluoride (fluoride group), with resveratrol (12.5mg/kg i.p., resveratrol group), or with 100ppm fluoride+12.5mg/kg resveratrol i.p. (fluoride+resveratrol group). At the end of the trial, blood samples were collected by cardiac puncture and tissue samples were taken simultaneously. The total antioxidant and oxidant status in plasma and tissues as well as plasma 8-hydroxydeoxyguanosine levels were measured. Histopathological analyses of rat liver and brain tissues were performed in all groups to identify any changes. In the fluoride group, the total oxidant levels increased in plasma, liver and brain and total antioxidant levels decreased, as did the plasma 8-hydroxy-deoxyguanosine levels. These changes were prevented by co-administration of resveratrol. In addition, fluoride-associated severe histopathological changes in brain and liver tissues were not observed in the fluoride+resveratrol group. Consequently, these data suggested that resveratrol had beneficial effects in alleviating fluoride-induced oxidative stress.
Toxoplasma gondii is an intracellular parasite with the potential of causing severe encephalitis among immunocompromised human and animals. The aim of this experimental study was to investigate the ...immunomodulatory and immunopathological role of nitric oxide (NO) in central nervous systems and to identify any correlation between toxoplasmosis neuropathology and investigate the consequences of the cellular responses protect against T. gondii. Mice were infected with ME49 strain T. gondii and levels of endothelial, neuronal and inducible nitric oxide synthase (eNOS, nNOS, iNOS), glial fibrillary acidic protein (GFAP) and neurofilament (NF) were examined in brain tissues by immunohistochemistry, during the development and establishment of a chronic infection at 10 30 and 60 days post infection. Results of the study revealed that the levels of eNOS (p < 0.05), nNOS (p < 0.05), iNOS (p < 0.005), GFAP (p < 0.005) and NF (p < 0.005) were remarkably higher in T. gondii-infected mice than in uninfected control. The most prominent finding from our study was 10 and 30 days after inoculation data indicating that increased levels of NO not only a potential neuroprotective role for immunoregulatory and immunopathological but also might be a molecular trigger of bradyzoite development. Furthermore, this findings were shown that high expressed NO origin was not only inducible nitric oxide synthase but also endothelial and neuronal. We demonstrated that activation of astrocytes and microglia/macrophages is a significant event in toxoplasma encephalitis (TE). The results also clearly indicated that increased levels of NO might contribute to neuropathology related with TE. Furthermore, expression of NF might gives an idea of the progress and critical for diagnostic significance of this disease.
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•NO has protective and neuropathological effects in the CNS in Toxoplasma gondii infection.•NF expression might be a useful prognostic indicator and monitoring in Toxoplasmic encephalitis pathogenesis.•Expression of NF provides insight into the severity of toxoplasmosis.
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