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Several studies demonstrated the toxicity of aspartame (ASP) and aflatoxin B 1 (AFB 1 ) in preclinical models. Although the majority of these reports assessed the toxic effects of each substance separately, their concomitant exposure and hazardous consequences are scarce. Importantly, the deleterious effects at the central nervous system caused by ASP and AFB 1 co-exposure are rarely addressed. We evaluated if concomitant exposure to AFB 1 and ASP would cause behavioral impairment and alteration in oxidative status of the brain in male rats. Animals received once a day for 14 days AFB 1 (250 µg/kg, intragastric gavage [i.g.]), ASP (75 mg/kg, i.g.), or both substances (association). On day 14, they were subjected to behavioral evaluation, and biochemical and molecular parameters of oxidative status were measured in the cerebral cortex and hippocampus. In the open field test, AFB 1 and combination treatments modified the motor, exploratory, and grooming behavior. In the splash test, all treatments caused a reduction in grooming time compared to the control group. An increase in thiobarbituric acid-reactive substances content induced by AFB 1 and combination treatments was observed. The antioxidant defenses (vitamin C, nonprotein sulfhydryl, and ferric reducing antioxidant power) were impaired in all groups compared to control. Regarding molecular evaluation, mitochondrial superoxide dismutase-2 immunoreactivity decreased after AFB 1 or ASP exposition in the hippocampus. Thus, co-exposure to ASP and AFB 1 was potentially more toxic because it aggravated behavioral impairments and oxidative status disbalance in comparison to the groups that received only ASP or AFB 1 . Therefore, our data suggest that those substances caused a disruption in brain homeostasis., (© 2023 Institute of Food Technologists.)

Aflatoxin B 1 (AFB 1 ) is the most common toxic mycotoxin that contaminates food. The treatment of its intoxication and the management of contaminations are a constant subject of health agendas worldwide. However, such efforts are not always enough to avoid population intoxication. Our objective was to investigate whether intermittent exposure to AFB 1 would cause any impairment in biochemical and behavioral parameters, intending to simulate an irregular consumption. Male Wistar rats received four AFB 1 administrations (250 μg/kg) by intragastric route separated by a 96-h interval. Toxicity was evaluated using behavioral tests (open field, object recognition, nest construction, marble burying, and splash test), biochemical markers of oxidative stress (cerebral cortex, hippocampus, liver, and kidneys), and plasma parameters of hepatic and renal functions. The intermittent exposure caused no modification in body weight gain as well as in organ weight. Both control and AFB 1 groups presented similar profiles of behavior to all tests performed. Furthermore, AFB 1 administrations alter neither antioxidant defenses nor markers of oxidation in all assayed tissues and in the plasma markers of hepatic and renal functions. Therefore, AFB 1 intermittent administration did not cause its common damage from exposure to this toxicant, which must be avoided, and additional studies are required.

The potential interactions among food additives/contaminants and the consequences to biological systems is a topic that is rarely addressed in scientific literature. Thus, the current study investigated if the combined administration of ASP and AFB 1 would impair hepatic and renal oxidative status. Male Wistar rats received during 14 days once a day ASP (75 mg/Kg) and/or AFB 1 (250 µg/Kg) through intragastric route. At the end of experimental protocol, samples of liver and kidneys were collected for assessing biochemical markers of oxidative status. In the hepatic tissue, the treatment with a single substance (ASP or AFB 1 ) caused an increase in TBARS levels, and a reduction in non-enzymatic antioxidant defenses (Vit C and NPSH levels and FRAP test). In the kidneys, TBARS levels were increased only in the group that received ASP + AFB 1 . The association reduced NPSH content, while the treatment with AFB 1 reduced the FRAP levels. GST and CAT activities were increased in all treatments. Overall, ASP and AFB1 association presented higher toxic effects to the tissues. To the best of our knowledge, this is the first study demonstrating that the associated use of both ASP and AFB1 induces more extensive injuries in comparison to the effects caused by each one alone. Therefore, these data demonstrated that concomitant exposure to ASP and AFB 1 potentiated their oxidative damage in hepatic tissue, suggesting that this organ is particularly sensitive to the toxic action induced by these substances.

Thousands of leprosy patients not only suffer from physical deformities, but also either have or have had hepatitis B virus (HBV) coinfection. Polymorphisms of the complement system modulate susceptibility to leprosy, but genetic susceptibility to past or present HBV infection is unknown. We used sequencing and multiplex sequence-specific PCR to genotype 72 polymorphisms of seven genes ( MBL2 , FCN1, FCN2, FCN3, MASP1, MASP2, C3 ) encoding components of the lectin pathway, and two genes encoding complement receptors ( CR1, VSIG4 ) in 190 patients, of which 74 were positive for HBsAg and/or anti-HBc (HBV+, 93.2% with a resolved infection) and 116 lepromatous patients, and 408 HBV-blood donors. In addition, we tested for levels of proteins of the lectin pathway. We found no difference between serum concentrations of mannan-binding lectin (MBL), MBL-associated serine proteins (MASP-1, MASP-2, MASP-3, MAp44), ficolin-3 (FCN-3), soluble complement receptor 1 (sCR1) and MBL mediated C4 activation, measured by ELISA or TRIFMA in up to 167 HBV+ and HBV- patients. Haplotypes lowering protein levels or encoding dysfunctional proteins increased susceptibility to HBV infection: MBL2*LYQC (OR = 3.4, p = 0.02), MASP1*AC_CC (OR = 4.0, p = 0.015) and MASP2*1C2-l (OR = 5.4, p = 0.03). Conversely, FCN1*3C2 haplotype, associated with higher gene expression, was protective (OR = 0.56, P = 0.033). Other haplotypes associated with HBV susceptibility were: MASP2*2B1-i (OR = 19.25, P = 0.003), CR1*3A (OR = 2.65, P = 0.011) and VSIG4*TGGRCG (OR = 12.55, P = 0.014). Some polymorphisms in ficolin genes associated with lower protein levels increased susceptibility to leprosy/HBV infection: FCN*1 (OR = 1.66, P = 0.029), FCN2*GGGCAC (OR = 6.73, P = 0.008), and FCN3*del_del_C (OR = 12.54, P = 0.037), and to lepromatous disease/HBV infection: FCN2*TA (OR = 2.5, P = 0.009), whereas FCN2*MAG was associated with increased FCN-2 expression and resistance against coinfection (OR = 0.29, P = 0.026). These associations were independent of demographic factors and did not increase susceptibility to leprosy per se , except MASP2*1C2-l . Associations for FCN2, FCN3, MASP1, MASP2 , and VSIG4 variants were also independent of each other. In conclusion, polymorphisms compromising activation of the lectin pathway of complement increase susceptibility to HBV infection, with ficolin polymorphisms playing a major role in modulating the susceptibility among leprosy patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Boldt, Oliveira-Toré, Kretzschmar, Weinschutz Mendes, Stinghen, Andrade, Bumiller-Bini, Gonçalves, Braga, Stahlke, Velavan, Thiel and de Messias-Reason.)

Introduction: The efficacy of cardiopulmonary exercise testing (CPET) to determining exercise intensity has not been established in Amyotrophic Lateral Sclerosis (ALS). We studied this intervention., Methods: We included 48 ALS patients randomized in 2 groups: G1 ( n = 24), exercise intensity leveled by CPET; G2 ( n = 24), standard care limited by fatigue, during 6 months. ALS functional scale (ALSFRS-R) and forced vital capacity (FVC) were performed every 3 months; CPET was done at admission ( T 1) and 6 months later ( T 2). We registered oxygen uptake, carbon dioxide output, and ventilation at anaerobic threshold and at peak effort. Primary outcome was functional change. We used parametric statistics for comparisons and multiple regression analyses to identify independent predictors of functional decline., Results: At T 1 both groups were identical, except for higher FVC in G1 ( p = 0.02). At T 2, ALSFRS-R was higher ( p = 0.035) in G1. Gas exchange variables at T 2 did not change in G1 but had significant differences in G2 ( p < 0.05). Multiregression analyses showed the Spinal ALSFRS-R slope and Intervention group ( p < 0.001) as significant predictors of ALSFRS-R at T 2., Conclusion: Aerobic exercise defined by CPET is feasible and can improve functional outcome in ALS. This trial is registered with Clinical trials.gov ID: NCT03326622.

Fu monisin B 1 (FB 1 ) is a mycotoxin commonly found in maize and maize-based products. Ingestion of FB 1 -contaminated causes a myriad of dose- and species-dependent toxic effects to human and animal health. In the present study we evaluated the effects of FB 1 (8 mg/kg, i.p. for 4 days) on body weight and oxidative stress parameters in the liver, kidney and lung of C57BL/6 male mice. No changes in the organ-to-body weight ratio, organ-to-adrenal gland weight ratio or organ-to-brain weight ratio were found. On the other hand, FB 1 exposure increased NPSH levels in liver and lungs whereas decreased FRAP content in liver and kidneys. Levels of TBARS, ascorbic acid and NOx content were not altered by FB 1 . In summary, four days of FB 1 exposure are sufficient to disrupt antioxidant defenses in liver, kidneys and lungs of C57BL/6 male mice without concomitant changes in organs weight.