Therapeutic potential of hydantoin and thiohydantoin compounds against Schistosoma mansoni: An integrated in vitro, DNA, ultrastructural, and ADMET in silico approach.

The study aimed to conduct in vitro biological assessments of hydantoin and thiohydantoin compounds against mature Schistosoma mansoni worms, evaluate their cytotoxic effects and predict their pharmacokinetic parameters using computational methods. The compounds showed low in vitro cytotoxicity and were not considered hemolytic. Antiparasitic activity against adult S. mansoni worms was tested with all compounds at concentrations ranging from 200 to 6.25 µM. Compounds SC01, SC02, and SC03 exhibited low activity. Compounds SC04, SC05, SC06 and SC07 caused 100 % mortality within 24 h of incubation at a concentration of 100 and 200 µM. Thiohydantoin SC04 exhibited the highest activity, resulting in 100 % mortality after 24 h of incubation at a concentration of 50 µM and IC50 of 28 µM. In the ultrastructural analysis (SEM), the compound SC04 (200 µM) induced integumentary changes, formation of integumentary blisters, and destruction of tubercles and spicules. Therefore, the SC04 compound shows promise as an antiparasitic against S. mansoni.

Sanguinarine: an alkaloid with promising in vitro and in vivo antiparasitic activity against different developmental stages of Schistosoma mansoni and in silico pharmacokinetic properties (ADMET).

The objective of the study was to evaluate the in vitro and in vivo schistosomicidal activity of sanguinarine (SA) on Schistosoma mansoni and its in silico pharmacokinetic parameters. ADMET parameters and oral bioavailability were evaluated using the PkCSM and SwissADME platforms, respectively. The activity of SA in vitro, at the concentrations of 1.0-25 µM, was analyzed through the parameters of motility, mortality, and cell viability of the worms at intervals of 3-24 h. Mice were infected with cercariae and treated by gavage with SA (5 mg/kg/day, in a single dose or two doses of 2.5 mg/kg every 12 h for 5 consecutive days) on the 1st (skin schistosomula), 14th (pulmonary schistosomula), 28th (young worms), and 45th (adult worms) days after infection. In vitro and in vivo praziquantel was the control. In vitro, SA showed schistosomicidal activity against schistosomula, young worms, and couples; with total mortality and reduced cell viability at low concentrations and incubation time. In a single dose of 5 mg/kg/day, SA reduces the total worm load by 47.6%, 54%, 55.2%, and 27.1%, and female worms at 52.0%, 39.1%, 52.7%, and 20.2%, respectively, results which are similar to the 2.5 mg/kg/day dose. SA reduced the load of eggs in the liver, and in histopathological and histomorphometric analyses, there was a reduction in the number and volume of hepatic granulomas, which exhibited less inflammatory infiltrate. SA has promising in vitro and in vivo schistosomicidal activity against different developmental stages of S. mansoni, in addition to reducing granulomatous liver lesions. Furthermore, in silico, SA showed good predictive pharmacokinetic ADMET profiles.

Effects of the probiotic Bacillus cereus GM on experimental schistosomiasis mansoni.

Probiotics contribute to the integrity of the intestinal mucosa and preventing dysbiosis caused by opportunistic pathogens, such as intestinal helminths. Bacillus cereus GM obtained from Biovicerin® was cultured to obtain spores for in vivo evaluation on experimental schistosomiasis. The assay was performed for 90 days, where all animals were infected with 50 cercariae of Schistosoma mansoni on the 15th day. Three experimental groups were formed, as follows: G1-saline solution from the 1st until the 90th day; G2-B. cereus GM (105 spores in 300 µL of sterile saline) from the 1st until the 90th day; and G3-B. cereus GM 35th day (onset of oviposition) until the 90th day. G2 showed a significant reduction of 43.4% of total worms, 48.8% of female worms and 42.5% of eggs in the liver tissue. In G3, the reduction was 25.2%, 29.1%, and 44% of the total number of worms, female worms, and eggs in the liver tissue, respectively. G2 and G3 showed a 25% (p < 0.001) and 22% (p < 0.001) reduction in AST levels, respectively, but ALT levels did not change. ALP levels were reduced by 23% (p < 0.001) in the G2 group, but not in the G3. The average volume of granulomas reduced (p < 0.0001) 65.2% and 46.3% in the liver tissue and 83.0% and 53.2% in the intestine, respectively, in groups G2 and G3. Th1 profile cytokine (IFN-γ, TNF-α, and IL-6) and IL-17 were significantly increased (p < 0.001) stimulated with B. cereus GM in groups G2 and G3. IL-4 showed significant values when the stimulus was mediated by ConA. By modulating the immune response, B. cereus GM reduced the burden of worms, improved some markers of liver function, and reduced the granulomatous inflammatory reaction in mice infected with S. mansoni, especially when administered before infection.

Superimposing a high-fat diet on schistosoma mansoni infection affects renin-angiotensin system components in the mouse kidney

Abstract INTRODUCTION: The levels of the full-length form of the (pro)renin receptor (PRR), a component of the renin-angiotensin system (RAS), may be reduced in the membranes of kidneys in renal diseases. This study aimed to investigate the RAS components in the kidneys of mice submitted to a combination of a high-fat diet and Schistosoma mansoni infection. METHODS: Female BALB/c mice were maintained on a control or high-fat diet from 3 weeks of age. After 10 weeks on the designated diets, half the mice in each group were infected with S. mansoni cercariae. The blood and kidneys were harvested 8 weeks after infection. RESULTS: The high-fat diet increased the number of eggs in the feces and the number of adult worms in the mesenteric bed. Schistosoma mansoni infection reduced the plasma levels of glucose, triglycerides, and HDL cholesterol in the control and high-fat diet groups. In mice on the control diet, S. mansoni infection resulted in increased expression of IL-6 in the kidneys; however, in mice on the high-fat diet, the levels of IL-6 were reduced and those of superoxide anions were increased. The RAS components evaluated were ACE2, renin, PRR, AT1R, and AT2R, and the levels of PRR were found to be reduced in the kidneys of infected mice on the high-fat diet. CONCLUSIONS: The finding regarding PRR is not yet clear. However, combining a high-fat diet and S. mansoni infection resulted in increased oxidative stress in the kidney that can aggravate hypertension as well as its associated complications.

Influência da Esplenectomia Total na Microbiota Intestinal, na Translocação Bacteriana e na Evolução da Sepse em Modelo Experimental / Influence of Total Splenectomy on Intestinal Microbiota, Bacterial Translocation and Sepsis Evolution in Experimental Model

A esplenectomia diminui a atividade de células imunes e pode estar relacionada com translocação bacteriana (TB) e sepse. Investigou-se a presença de TB e sepse em camundongos esplenectomizados, por meio de análises de peso, de sexo, de alterações da microbiota digestória e mucosa duodenal. 20 fêmeas e 20 machos de camundongos Swiss webster com 125 dias foram divididos em dois grupos: esplenectomizados e controles. Os animais foram pesados diariamente. Após sete dias da esplenectomia total convencional, os animais foram eutanasiados para estudo da TB, microbiota e morfometria intestinais. Para microbiota, foram coletadas as fezes da região média do intestino delgado, que foi seccionado para análise morfométrica. Após o preparo dos tubos com amostras fecais nas diferentes diluições, foram inoculados 0,1 mL de cada na superfície de placas contendo meios cromogênicos. Fragmentos do fígado e linfonodos mesentéricos foram macerados e homogeneizados, separadamente, em placas de Petri estéreis, posteriormente, adicionadas a caldo cérebro coração (BHI) na proporção de 1:5 e incubados em estufa a 37 °C por 24 horas. Posteriormente, alçadas de caldo foram semeadas em placas de Petri com diferentes meios de culturas. Os camundongos esplenectomizados apresentaram redução da evolução ponderal e maior prevalência de coproculturas positivas. A análise morfométrica duodenal revelou redução na altura e da área das vilosidades dos grupos esplenectomizados comparados aos seus controles. Os machos esplenectomizados apresentaram maiores taxas de TB e sepse. A asplênia aumenta a suscetibilidade à TB e, consequentemente, as doenças de origem séptica em camundongos. Sexo e alterações da mucosa duodenal podem influenciar no aumento deste fenômeno(AU)

Ssplenectomy diminishes the immune cells activity and may be related to bacterial translocation (BT) and sepsis. The BT and sepsis presence in splenectomized mice was investigated through analyzes of weight, sex, changes in the digestive microbiota and duodenal mucosa. Swiss Webster mice (20 females/20 males) were divided into two equal groups: splenectomized and controls, aged 125 days of life. Total splenectomy was performed in splenectomized group. The animals were weighed every day. After seven days, the animals were euthanized for the study of TB, microbiota and intestinal morphology. For microbiota study, stools were collected from the middle region of the small intestine, which was sectioned for morphometric analysis. After the tubes preparation with fecal samples at different dilutions, 0.1 mL of each sample was inoculated on the surface of plates containing chromogenic media. Fragments of the liver and mesenteric lymph nodes were macerated and homogenized separately in sterile Petri dishes, subsequently added to a brain/heart broth (BHI) in concentration 1:5 and incubated in an oven at 37 °C for 24 hours. Subsequently, the broths were seeded in Petri dishes with different culture media. The splenectomized mice presented a reduction in the ponderal evolution and a higher prevalence of positive coprocultures. Duodenal morphometric analysis revealed a reduction in the height and villus area of the splenectomized groups compared to their controls. Splenectomized males had higher BT and sepsis rates. Asplenia increases susceptibility to BT, and consequently septic diseases in mice. Sex and duodenal mucosa alterations may influence the increase of this phenomenon.(AU)