Changes in splenic tissue and immune response profile of Schistosoma mansoni infected mice submitted to chronic ethanol intake.

In Schistosoma mansoni infection, the spleen is one of the organs affected, causing its enlargement (splenomegaly). Intake of ethanol through alcoholic beverages can cause spleen atrophy and interfere with immune activity. To gain knowledge of this association on the spleen and on the immune response profile, male mice were used as an experimental model. These animals were divided into four groups: C. control; EC. uninfected/ethanol gavage; I. infected; and IE. infected/ethanol gavage. Groups I and IE were infected with about 100 cercariae (BH strain) of S. mansoni and in the fifth week of infection, gavage 200 µL/day/animal of 18 % ethanol was started for 28 consecutive days. At the end of the gavage (9th week of infection) all animals were euthanized. The spleen was removed and longitudinally divided in two parts. After histological processing, the sections were stained with H&E and Gomori's Reticulin for histopathological and stereological analyses, white pulp morphometry and quantification of megakaryocytes. The other fragment was macerated (in laminar flow) and the cell suspension, after adjusting the concentration (2 × 106), was plated to obtain cytokines produced by spleen cells that were measured by flow cytometry (Citometric Bead Array). Histopathological and quantitative analyzes in the spleen of the IE group showed an increase in the number of trabeculae and megakaryocytes, a decrease in reticular fibers, as well as important organizational changes in the white pulp and red pulp. Due to the decrease in the levels of cytokines measured and the result of the calculation of the ratio between the IFN-y and IL-10 cytokines (p = 0.0079) of the infected groups, we suggest that ethanol decreased the inflammatory and anti-inflammatory response generated by the infection (group IE, the production of cytokines was significantly decreased (p < 0.01). These changes demonstrate that ethanol ingestion interferes with some parameters of experimental S. mansoni infection, such as changes in splenic tissue and in the pattern of cytokine production.

Impact of acute schistosomiasis mansoni and long-term ethanol intake on mouse liver pathology.

While the effect of ethanol and schistosomiasis mansoni on liver injury has been well-documented, the influence of comorbidity on liver pathology remains unclear. To address this gap, schistosomiasis-infected mice were given one daily dose of 18% ethanol for 28 consecutive days, from day 35 post-infection. Mice were assigned to four groups: A. control; B. uninfected/ethanol gavage; C. infected; and D. infected/ethanol gavage. At day 64 post-infection, mice were euthanized by CO2 asphyxiation, livers were excised, fixed in 10% buffered formalin, paraffin embedded and cut into 5 µm sections. These were stained with hematoxylin and eosin (HE), Lennert's Giemsa and picrosirius red (for polarization microscopy) to assess histopathological and stereological changes. Group B showed alcoholic liver disease (ALD), including microsteatosis, hepatocyte karyopyknosis, karyorrhexis, karyolysis, increased frequency of Kupffer cells, hydropic degeneration of hepatocyte, thickened plasma membrane and binucleated hepatocytes. Infected mice showed typical exudative and exudative-productive hepatic granulomas, and destruction of the adjacent hepatic parenchyma, resulting in necrotic tissue and periovular leukocyte infiltrate. Group D showed hyperemia (parenchymal panlobular lesions), and liquefactive necrosis in hepatic abscess area. There was also reduced liver collagen deposition (-76%; p = 0.0001) and reduced microsteatosis (-80%, p = 0.0079) compared to group C and group B, respectively. In conclusion, comorbidity exacerbated liver damage.

Effects of multiple doses of simvastatin and artesunate monotherapy on SCHISTOSOMA MANSONI adult worms during infection in hyperlidemic mice / Efectos de múltiples dosis de simvastatina y artesunato en monoterapia en gusanos adultos de SCHISTOSOMA MANSONI durante la infección en ratones hiperlidémicos / Efeitos de doses múltiplas de monoterapia com sinvastatina e artesunato em vermes adultos SCHISTOSOMA MANSONI durante a infecção em camundongos hiperlidêmicos

A single dose of simvastatin and of artesunate monotherapy cause damage to the reproductive system of schistosomes as well as severe tegumental damage in male worms recovered from mice fed high-fat chow. This study aims to investigate whether treatment with multipledose regimes may offer more antischistosomal activity advantages than single daily dosing in mice fed high-fat chow. For this purpose, nine weeks post-infection, Swiss Webster mice were gavaged with simvastatin (200 mg/kg) or artesunate (300 mg/kg) for five consecutive days and euthanized two weeks post-treatment. Adult worms were analyzed using brightfield microscopy, confocal microscopy and scanning electron microscopy, presenting damages caused by simvastatin and artesunate to the reproductive system of males and females as well as tegument alterations, including peeling, sloughing areas, loss of tubercles, tegumental bubbles and tegument rupture exposing subtegumental tissue. The overall findings in this study revealed the potential antischistosomal activity of simvastatin and artesunate against Schistosoma mansoni adult worms, in addition to showing that multiple doses of either monotherapy caused severe damage to the tegument.

Una sola dosis de simvastatina y de artesunato en monoterapia causa daño al sistema reproductivo de los esquistosomas, así como daño tegumental severo en gusanos machos recuperados de ratones alimentados con comida rica en grasas. Este estudio tiene como objetivo investigar si el tratamiento con regímenes de dosis múltiples puede ofrecer más ventajas de actividad antiesquistosomal que la dosis única diaria en ratones alimentados con comida rica en grasas. Para este propósito, nueve semanas después de la infección, los ratones Swiss Webster se alimentaron por sonda con simvastatina (200 mg / kg) o artesunato (300 mg / kg) durante cinco días consecutivos y se sacrificaron dos semanas después del tratamiento. Los gusanos adultos se analizaron utilizando campo claro microscopía, microscopía confocal y microscopía electrónica de barrido, presentando daños causados ​​por simvastatina y artesunato en el sistema reproductivo de machos y hembras, así como alteraciones del tegumento, incluyendo descamación, desprendimiento, pérdida de tubérculos, burbujas tegumentales y rotura del tegumento exponiendo tejido subtegumental. Los hallazgos generales de este estudio revelaron la posible actividad antiesquistosomal de la simvastatina y el artesunato contra los gusanos adultos de Schistosoma mansoni, además de mostrar que dosis múltiples de cualquiera de las dos monoterapia causaron daños graves al tegumento.

Uma única dose de sinvastatina e de monoterapia com artesunato causa danos ao sistema reprodutivo dos esquistossomos, bem como danos graves ao tegumento em vermes machos recuperados de camundongos alimentados com ração rica em gordura. Este estudo tem como objetivo investigar se o tratamento com regimes de múltiplas doses pode oferecer mais vantagens da atividade anti-esquistossomótica do que uma única dose diária em ratos alimentados com ração rica em gordura. Para tanto, nove semanas após a infecção, camundongos Swiss Webster foram inoculados com sinvastatina (200 mg / kg) ou artesunato (300 mg / kg) por cinco dias consecutivos e sacrificados duas semanas após o tratamento. Vermes adultos foram analisados ​​usando campo claro microscopia, microscopia confocal e microscopia eletrônica de varredura, apresentando danos causados ​​pela sinvastatina e artesunato ao sistema reprodutivo de homens e mulheres, bem como alterações do tegumento, incluindo descamação, áreas de descamação, perda de tubérculos, bolhas tegumentais e ruptura do tegumento com exposição de tecido subtegumentar. Os achados gerais deste estudo revelaram a potencial atividade anti-esquistossomótica da sinvastatina e do artesunato contra vermes adultos do Schistosoma mansoni, além de mostrar que doses múltiplas de ambas as monoterapias causaram danos graves ao tegumento.

Long-term ethanol intake causes morphological changes in Schistosoma mansoni adult worms in mice.

Schistosoma mansoni adult worms are extensively challenged by reactive oxygen species from intrinsic sources. However, the effects of extrinsic sources such as ethanol have not been looked at in schistosomes. We examined adult worms recovered from ethanol-consuming mice by light (LM), confocal (CM) and scanning electron microscopy (SEM) to address this question. Schistosomiasis-infected mice were orally gavaged with 18% (v/v) ethanol from 35 to 63 days post-infection, when they were euthanized. CM examination revealed reduced germ cells density (-36%, p = 0.0001) and sperm density (-58%, p = 0.0001) in testicular lobes, and immature cells in seminal vesicle compared to unexposed control worms. Female worms showed reduced density of vitellin glands (-71%, p = 0.0001), maturation of oocytes (-7%, p = 0.0071) and reduced spermatozoa density (-23%, p = 0.0002) within the seminal receptacle. SEM revealed remarkable damages in male's tegument, including tubercles flattening, tegumental peeling and erosive lesions. Given that lipids are present in reproductive system and tegument, our results suggest that phenotypic changes are due to ethanol-induced lipid peroxidation. To the best of our knowledge, this is the first report revealing the biological action of ethanol intake on adult schistosomes in vivo.