Protective action of N-acetyl-L-cysteine associated with a polyvalent antivenom on the envenomation induced by Lachesis muta muta (South American bushmaster) in rats

In this study, we examined the potential use of N-acetyl-L-cysteine (NAC) in association with a polyvalent antivenom and as stand-alone therapy to reduce the acute local and systemic effects induced by Lachesis muta muta venom in rats. Male Wistar rats (300–350 g) were exposed to L. m. muta venom (1.5 mg/kg – i.m.) and subsequently treated with anti-Bothrops/Lachesis serum (antivenom:venom ratio 1:3 ‘v/w’ – i.p.) and NAC (150 mg/kg – i.p.) separately or in association; the animals were monitored for 120 min to assess changes in temperature, locomotor activity, local oedema formation and the prevalence of haemorrhaging. After this time, animals were anesthetized in order to collect blood samples through intracardiac puncture and then euthanized for collecting tissue samples; the hematological-biochemical and histopathological analyses were performed through conventional methods. L. m. muta venom produced pronounced local oedema, subcutaneous haemorrhage and myonecrosis, with both antivenom and NAC successfully reducing the extent of the myonecrotic lesion when individually administered; their association also prevented the occurrence of subcutaneous haemorrhage. Venom-induced creatine kinase (CK) release was significantly prevented by NAC alone or in combination with antivenom; NAC alone failed to reduce the release of hepatotoxic (alanine aminotransferase) and nephrotoxic (creatinine) serum biomarkers induced by L. m. muta venom. Venom induced significant increase of leucocytes which was also associated with an increase of neutrophils, eosinophils and monocytes; antivenom and NAC partially reduced these alterations, with NAC alone significantly preventing the increase of eosinophils whereas neither NAC or antivenom prevented the increase in monocytes. Venom did not induce changes in the erythrogram parameters. In the absence of a suitable antivenom, NAC has the potential to reduce a number of local and systemic effects caused by L. m. muta venom

Effects of patulin and ascladiol on porcine intestinal mucosa: An ex vivo approach

Patulin (PAT) is a secondary metabolite mainly produced by Aspergillus and Penicillium that is frequently found contaminating apples and rotten fruits. Patulin can be transformed in potentially less toxic compounds such as ascladiol (ASC). Toxic effects of patulin were described in rats and in in vitro models, however concerning ascladiol, data are restricted to metabolic pathways. The aim of the present study was to evaluate the effects of different concentrations of PAT (10 mu M, 30 mu M,100 mu M) and ASC (30 mu M, 100 mu M) on intestinal tissue using the jejunal explant model. Explants from pigs were exposed for 4 h to PAT and ASC and after this period were processed for histological, morphometrical and immunohistochemical analysis. Mild histological changes were observed in jejunal explants exposed to PAT and ASC, however no significant difference in the lesional score or villi height was observed between the PAT/ASCgroups and the control. Also, explants exposed to 100 mu M of PAT showed a significant decrease in goblet cells density and a significant increase in cell apoptosis. These results indicate that high levels of patulin can induce mild toxic effects on intestinal mucosa whereas ascladiol apparently is non-toxic to intestinal tissue

Phytic Acid Decreases Oxidative Stress and Intestinal Lesions Induced by Fumonisin B1 and Deoxynivalenol in Intestinal Explants of Pigs

The purpose of the present study was to investigate the effects of phytic acid (IP6) on morphological and immunohistochemical parameters and oxidative stress response in intestinal explants of pigs exposed to fumonisin B1 (FB1) and/or deoxynivalenol (DON). The jejunal explants were exposed to the following treatments: vehicle, IP6 5 mM, DON 10 µM, FB1 70 µM, DON 10 µM + FB1 70 µM, DON 10 µM + IP6 5 mM, FB1 70 µM + IP6 5 mM, and DON 10 µM + FB1 70 µM + IP6 5 mM. The decrease in villus height and goblet cell density was more evident in DON and DON + FB1 treatments. In addition, a significant increase in cell apoptosis and cell proliferation and a decrease in E-cadherin expression were observed in the same groups. DON and FB1 exposure increased cyclooxygenase-2 expression and decreased the cellular antioxidant capacity. An increase in lipid peroxidation was observed in DON- and FB1-treated groups. IP6 showed beneficial effects, such as a reduction in intestinal morphological changes, cell apoptosis, cell proliferation, and cyclooxygenase-2 expression, and an increase in E-cadherin expression when compared with DON, FB1 alone, or DON and FB1 in association. IP6 inhibited oxidative stress and increased the antioxidant capacity in the explants exposed to mycotoxins