No abstract

This study used a murine model of Chagas disease to investigate the isolated and combined impact of Trypanosoma cruzi infection and benznidazole (BZ) therapy on liver structure and function. Male C57BL/6 mice were challenged with T. cruzi and BZ for 15 days. Serum levels of cytokines and hepatic enzymes, liver oxidative stress, morphology, collagen, and glycogen content were monitored. Separately, T. cruzi infection and BZ treatment resulted in a pro-oxidant status and hepatic reactive damage. Concurrently, both T. cruzi infection and BZ treatment induced upregulation of antioxidant enzymes and pathological reorganization of the liver parenchyma and stroma. T. cruzi infection increased serum levels of Th1 cytokines, which were reduced by BZ in both infected and non-infected animals. BZ also induced functional organ damage, increasing serum levels of liver enzymes. When combined, T. cruzi infection and BZ therapy elicited intense hepatic reactive damage that was not compensated by antioxidant enzymatic reaction, subsequently culminating in more severe morphofunctional hepatic injury. Taken together, these findings indicate that during specific treatment of Chagas disease, hepatic pathology may be a result of an interaction between BZ metabolism and specific mechanisms activated during the natural course of T. cruzi infection, rather than an isolated toxic effect of BZ on liver structure and function.

cAlthough suramin (Sur) is suggested as a potential drug candidate in the management of Chagas disease, this issue has not been objectively tested. In this study, we examined the applicability of concomitant treatment with benznidazole (Bz) and suramin in mice infected with a virulent strain of Trypanosoma cruzi. Eighty 12-week-old male C57BL/6 mice were equally randomized in eight groups: (i) noninfected mice (negative control) and mice infected with T. cruzi Y strain receiving (ii) no treatment (positive control), (iii) Bz, 100 mg/kg of body weight per day, (iv) Sur, 20 mg/kg/day, and (v to viii) Sur, 20 mg/kg/day, combined with Bz, 100, 50, 25, or 5 mg/kg/day. Bz was administered by gavage, and Sur was administered intraperitoneally. Sur dramatically increased the parasitemia, cardiac content of parasite DNA, inflammation, oxidative tissue damage, and mortality. In response to high parasitic load in cardiac tissue, Sur stimulated the immune system in a manner typical of the acute phase of Chagas disease, increasing tissue levels of gamma interferon (IFN-␥) and tumor necrosis factor alpha (TNF-␣) and inducing a preferential IgG2a anti-T. cruzi serum pattern. When Sur and Bz were combined, the infection severity was attenuated, showing a dose-dependent Bz response. Sur therapy had a more harmful effect on the host than on the parasite and reduced the efficacy of Bz against T. cruzi infection. Considering that Sur drastically reinforced the infection evolution, potentiating the inflammatory process and the severity of cardiac lesions, the in vivo findings contradicted the in vitro anti-T. cruzi potential described for this drug.

This study investigated the effect of the bark extract of Bathysa cuspidata on paraquat (PQ)-induced extra-pulmonary acute lung injury (ALI) and mortality in rats. ALI was induced with a single dose of PQ (30 mg/kg, i.p.), and animals were treated with B. cuspidata extract (200 and 400 mg/kg). Analyses were conducted of survival, cell migration, lung oedema, malondialdehyde, proteins carbonyls, catalase, superoxide dismutase, histopathology and the stereology of lung tissue. Rats exposed to PQ and treated with 200 and 400 mg of the extract presented lower mortality (20% and 30%), compared with PQ alone group (50%). Furthermore, lung oedema, septal thickening, alveolar collapse, haemorrhage, cell migration, malondialdehyde and proteins carbonyl levels decreased, and catalase and superoxide dismutase activity were maintained. These results show that the bark extract of B. cuspidata reduced PQ-induced extra-pulmonary ALI and mortality in rats and suggest that these effects may be associated with the inhibition of oxidative damage.

This study investigated the relationship between germ and Leydig cell death, testosterone, and adiponectin levels in cadmium-mediated acute toxicity. Cadmium chloride was administered in a single dose to five groups of rats: G1 (0.9% NaCl) and G2 to G5 (0.67, 0.74, 0.86, and 1.1 mg Cd/kg). After 7 days, the animals were euthanized, and the testosterone and testes were analyzed. Dose-dependent Cd accumulation in the testes was identified. At 0.86 and 1.1 mg/kg, animals exhibited marked inflammatory infiltrate and disorganization of the seminiferous epithelium. While Leydig cells were morphologically resistant to Cd toxicity, massive germ cell death and DNA oxidation and fragmentation were observed. Although numerical density of Leydig cells was unchanged, testosterone levels were significantly impaired in animals exposed to 0.86 and 1.1 mg Cd/kg, occurring in parallel with the reduction in total adiponectins and the increase in high-molecular weight adiponectin levels. Our findings indicated that Leydig and germ cells exhibit differential microstructural resistance to Cd toxicity. While germ cells are a primary target of Cd-induced toxicity, Leydig cells remain resistant to death even when exposed to high doses of Cd. Despite morphological resistance, steroidogenesis was drastically impaired by Cd exposure, an event potentially related to the imbalance in adiponectin production.

This study investigates the influence of gallium-arsenide (GaAs) laser photobiostimulation applied with different energy densities on skin wound healing by secondary intention in rats. Three circular wounds, 10 mm in diameter, were made on the dorsolateral region of 21 Wistar rats weighting 282.12 ± 36.08 g. The animals were equally randomized into three groups: Group SAL, saline solution 0.9%; Group L3, laser GaAs 3 J/cm(2); Group L30, laser GaAs 30 J/cm(2). Analyses of cells, blood vessels, collagen and elastic fibres, glycosaminoglycans and wound contraction were performed on the scar tissue from different wounds every 7 days for 21 days. On day 7, 14 and 21, L3 and L30 showed higher collagen and glycosaminoglycan levels compared to SAL (P < 0.05). At day 21, elastic fibres were predominant in L3 and L30 compared to SAL (P < 0.05). Type-III collagen fibres were predominant at day 7 in both groups. There was gradual reduction in these fibres and accumulation of type-I collagen over time, especially in L3 and L30 compared with SAL. Elevated density of blood vessels was seen in L30 on days 7 and 14 compared to the other groups (P < 0.05). On these same days, there was higher tissue cellularity in L3 compared with SAL (P < 0.05). The progression of wound closure during all time points investigated was higher in the L30 group (P < 0.05). Both energy densities investigated increased the tissue cellularity, vascular density, collagen and elastic fibres, and glycosaminoglycan synthesis, with the greater benefits for wound closure being found at the density of 30 J/cm(2).

The objective of this study was to investigate the hepatoprotective effect of a bark extract of Bathysa cuspidata extract (BCE) in a murine model of severe liver injury induced by carbon tetrachloride (CCl(4) ). Forty-two Wistar rats were randomized into six groups of seven animals each: Group 1(G1): CCl(4) ; Group 2 (G2): dimethyl sulfoxide (DMSO) + CCl(4) ; Group 3 (G3): BCE 400 mg/kg alone; Group 4 (G4): BCE 200 mg/kg + CCl(4) ; Group 5 (G5): BCE 400 mg/kg + CCl(4) ; Group 6 (G6): DMSO alone. The extract was administered by gavage for 18 days beginning 6 days prior to the first application of CCl(4) . After completing CCl(4) administration, the animals were euthanized. The animals in G1, G2, G4 and G5 experienced significant body weight loss and had an increased liver somatic index compared with G3 and G6 (P < 0.05). A significant reduction in serum aspartate and alanine transaminase and gamma-glutamyl transferase (P < 0.05) and a significant increase in the activity of the anti-oxidant enzyme superoxide dismutase were found in G5 (P < 0.05). Lower proportions of cellular necrosis and lipid droplets were found in the livers of animals in G4 and G5 compared with G1 and G2 (P < 0.05). These results confirm the marked hepatoprotective activity of the bark extract of Bathysa cuspidata in severe injuries induced by CCl(4) in rats and suggest that this effect may be associated with the inhibition of oxidative damage.

The technological development of pharmaceutical products based on plant extracts is currently responsible for a large number of recent innovations in healthcare. The objective of this study was to develop and investigate the effect and potential applicability of an ointment-based Bathysa cuspidata extract (BCE) for the management of skin wounds in rats. Threeskin wounds of 12 mm in diameter were made on the backs of the animals, which were randomized into 4 groups according to the application received, i.e. the SAL group: 0.9% saline solution, the LAN group: lanolin, the BCE 2.5% group: 2.5% BCE emulsified in lanolin and the BCE 5% group: 5% BCE emulsified in lanolin. The applications were made daily over 21 days, and every 7 days tissue from different wounds was removed. On days 7, 14 and 21, the BCE 2.5% and BCE 5% groups showed the best results in relation to wound closure, and a higher proportion (in length, density and volume) of blood vessels and fibroblasts compared to the other groups. On days 7 and 14, there was a significant increase in the number of mast cells in these 2 groups when compared to the SAL and LAN groups. On day 21, they also had a higher proportion of collagen I than collagen III. B. cuspidata in an ointment base was effective in stimulating tissue cellularity, mast cell recruitment, neoangiogenesis, synthesis and maturation of collagen, epidermal thickness and surface area in scar tissue. These events were potentially related to the best quality and speed for skin regeneration in the rats treated with the BCE ointment.