Aflatoxin B1 (AFB1) is the most widespread mycotoxin, and it is a feed contaminant and is highly toxic, causing carcinogenic, mutagenic, and teratogenic effects. Many researches clarified the ...peripheral effects of the exposition to AFB1; however, there are few studies explaining their effects on central nervous system. The aim of the present study was to evaluate the effects caused by acute oral administration of AFB1 on behavioral tests and selected biochemical parameters.
Young male Wistar rats received a single administration of AFB1 (250 µg/kg/i.g.) and 48 hours thereafter they were subjected to behavioral analysis. After the tests, biochemical parameters were measured in the cerebral cortex.
Acute treatment with AFB1 caused neurotoxic effects, evidenced by a significant reduction in the levels of non-enzymatic antioxidant defenses, ascorbic acid, and non-protein sulfhydryl groups. In addition, AFB1 increased protein kinase C (PKC) activation, evidenced by an increase in phosphorylation of Ser
of PKCα.
In this acute protocol, a single oral administration of AFB1 was able to cause changes in important neurochemical parameters, without concomitant, detectable behavioral alterations. These results reinforce that monitoring mycotoxin levels in food is essential to guarantee food security.
Celotno besedilo
Dostopno za:
DOBA, FSPLJ, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Traumatic brain injury (TBI) is a highly complex multi-factorial disorder. Experimental trauma involves primary and secondary injury cascades that underlie delayed neuronal dysfunction and death. ...Mitochondrial dysfunction and glutamatergic excitotoxicity are the hallmark mechanisms of damage. Accordingly, a successful pharmacological intervention requires a multi-faceted approach. Guanosine (GUO) is known for its neuromodulator effects in various models of brain pathology, specifically those that involve the glutamatergic system. The aim of the study was to investigate the GUO effects against mitochondrial damage in hippocampus and cortex of rats subjected to TBI, as well as the relationship of this effect with the glutamatergic system. Adult male Wistar rats were subjected to a unilateral moderate fluid percussion brain injury (FPI) and treated 15 min later with GUO (7.5 mg/kg) or vehicle (saline 0.9%). Analyses were performed in hippocampus and cortex 3 h post-trauma and revealed significant mitochondrial dysfunction, characterized by a disrupted membrane potential, unbalanced redox system, decreased mitochondrial viability, and complex I inhibition. Further, disruption of Ca
homeostasis and increased mitochondrial swelling was also noted. Our results showed that mitochondrial dysfunction contributed to decreased glutamate uptake and levels of glial glutamate transporters (glutamate transporter 1 and glutamate aspartate transporter), which leads to excitotoxicity. GUO treatment ameliorated mitochondrial damage and glutamatergic dyshomeostasis. Thus, GUO might provide a new efficacious strategy for the treatment acute physiological alterations secondary to TBI.
Aflatoxin B1 (AFB1) 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 AFB1 would cause any impairment in biochemical and behavioral parameters, intending to simulate an irregular consumption. Male Wistar rats received four AFB1 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 AFB1 groups presented similar profiles of behavior to all tests performed. Furthermore, AFB1 administrations alter neither antioxidant defenses nor markers of oxidation in all assayed tissues and in the plasma markers of hepatic and renal functions. Therefore, AFB1 intermittent administration did not cause its common damage from exposure to this toxicant, which must be avoided, and additional studies are required.
Caffeine is presented in many commercial products and has been proven to induce ergogenic effects in exercise, mainly related to redox status homeostasis, inflammation and oxidative stress-related ...adaptation mechanisms. However, most studies have mainly focused on muscle adaptations, and the role of caffeine in different tissues during exercise training has not been fully described. The aim of this study was therefore, to analyze the effects of chronic caffeine intake and exercise training on liver mitochondria functioning and plasma inflammation markers. Rats were divided into control, control/caffeine, exercise, and exercise/caffeine groups. Exercise groups underwent four weeks of swimming training and caffeine groups were supplemented with 6 mg/kg/day. Liver mitochondrial swelling and complex I activity, and plasma myeloperoxidase (MPO) and acetylcholinesterase (AChE) activities were measured. An anti-inflammatory effect of exercise was evidenced by reduced plasma MPO activity. Additionally, caffeine intake alone and combined with exercise decreased the plasma AChE and MPO activities. The per se anti-inflammatory effect of caffeine intake should be highlighted considering its widespread use as an ergogenic aid. Therefore, caffeine seems to interfere on exercise-induced adaptations and could also be used in different exercise-related health treatments.
Monosialoganglioside (GM1) is a glycosphingolipid that protects against some neurological conditions, such as seizures and ischemia. Glutaric acidemia type I (GA-I) is an inherited disease ...characterized by striatal degeneration, seizures, and accumulation of glutaric acid (GA). In this study, we show that GA inhibits Na
+,K
+-ATPase activity and increases oxidative damage markers (total protein carbonylation and thiobarbituric acid-reactive substances—TBARS) production in striatal homogenates from rats in vitro and ex vivo. It is also shown that GM1 (50 mg/kg, i.p., twice) protects against GA-induced (4 μmol/striatum) seizures, protein carbonylation, TBARS increase, and inhibition of Na
+,K
+-ATPase activity ex vivo. Convulsive episodes induced by GA strongly correlated with Na
+,K
+-ATPase activity inhibition in the injected striatum but not with oxidative stress marker measures. Muscimol (46 pmol/striatum), but not MK-801 (3 nmol/striatum) and DNQX (8 nmol/striatum) prevented GA-induced convulsions, increase of TBARS and protein carbonylation and inhibition of Na
+,K
+-ATPase activity. The protection of GM1 and muscimol against GA-induced seizures strongly correlated with Na
+,K
+-ATPase activity maintenance ex vivo. In addition, GM1 (50–200 μM) protected against Na
+,K
+-ATPase inhibition induced by GA (6 mM) but not against oxidative damage in vitro. GM1 also decreased pentylenetetrazole (PTZ)-induced (1.8 μmol/striatum) seizures, Na
+,K
+-ATPase inhibition, and increase of TBARS and protein carbonyl in the striatum. These data suggest that Na
+,K
+-ATPase and GABA
A receptor-mediated mechanisms may play important roles in GA-induced seizures and in their prevention by GM1.
Abstract Although the importance of brain trauma as risk factor for the development of epilepsy is well established, the mechanisms of epileptogenesis are not well understood. In the present study, ...we revealed that the injection of a subthreshold dose of PTZ (30 mg/Kg, i.p.) after 5 weeks of injury induced by Fluid Percussion Brain Injury (FPI) decreased latency for first clonic seizures, increased the time of spent generalized tonic–clonic seizures and electrocorticographic (EEG) wave amplitude. In addition, statistical analysis revealed that N -acetylcysteine (NAC) (100 mg/kg) supplementation during 5 weeks after neuronal injury protected against behavioral and electrographical seizure activity elicited by subthreshold dose of PTZ. The supplementation of this antioxidant compound also protected against the Na+ ,K+ -ATPase activity inhibition and concomitant increase in the levels of oxidative stress markers (protein carbonylation and thiobarbituric acid-reactive substances-TBARS) in site and peri-contusional cortical tissue. In summary, the current experiments clearly showed that FPI model induces early posttraumatic seizures and suggest that an alteration in the lipid/protein oxidation, membrane fluidity, and Na+ ,K+ -ATPase activity may be correlated with neuronal excitability, a significant component of the secondary injury cascade that accompanies TBI.
Summary
Purpose: In the present study we decided to investigate whether physical exercise protects against the electrographic, oxidative, and neurochemical alterations induced by subthreshold to ...severe convulsive doses of pentyltetrazole (PTZ).
Methods: The effect of swimming training (6 weeks) on convulsive behavior induced by PTZ (30, 45, and 60 mg/kg, i.p.) was measured and different electrographic electroencephalography (EEG) frequencies obtained from freely moving rats. After EEG recordings, reactive oxygen species (ROS) generation, nonprotein sulfhydryl (NPS), protein carbonyl, thiobarbituric acid‐reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT), Na+, K+‐ATPase activity, and glutamate uptake were measured in the cerebral cortex of rats.
Results: We showed that physical training increased latency and attenuated the duration of generalized seizures induced by administration of PTZ (45 mg/kg). EEG recordings showed that physical exercise decreased the spike amplitude after PTZ administration (all doses). Pearson’s correlation analysis revealed that protection of physical training against PTZ‐induced seizures strongly correlated with NPS content, Na+, K+‐ATPase activity, and glutamate‐uptake maintenance. Physical training also increased SOD activity, NPS content, attenuated ROS generation per se, and was effective against inhibition of Na+, K+‐ATPase activity induced by a subthreshold convulsive dose of PTZ (30 mg/kg). In addition, physical training protected against 2′,7′‐dichlorofluorescein diacetate (DCFH‐DA) oxidation, TBARS and protein carbonyl increase, decrease of NPS content, inhibition of SOD and catalase, and inhibition glutamate uptake induced by PTZ.
Conclusions: These data suggest that effective protection of selected targets for free radical damage, such as Na+, K+‐ATPase, elicited by physical training protects against the increase of neuronal excitability and oxidative damage induced by PTZ.
Abstract Physical exercise is likely to alter brain function and to afford neuroprotection in several neurological diseases. Although the favorable effects of physical exercise on traumatic brain ...injury (TBI) patients is well known, little information is available regarding the role of free radicals in the improvement induced by physical exercise in an experimental model of TBI induced by fluid percussion injury (FPI). Thus, we investigated whether 6 weeks of swimming training protects against oxidative damage (measured by protein carbonylation and thiobarbituric acid-reactive substances-TBARS) and neurochemical alterations represented by immunodetection of α subunit and activity of Na+ ,K+ -ATPase after FPI in cerebral cortex of rats. Statistical analysis revealed that physical training protected against FPI-induced TBARS and protein carbonylation increase. In addition, physical training was effective against Na+ ,K+ -ATPase enzyme activity inhibition and α1 subunit level decrease after FPI. Pearson's correlation analysis revealed that the decrease in levels of catalytic α1 subunit of Na+ ,K+ -ATPase induced FPI correlated with TBARS and protein carbonylation content increase. Furthermore, the effective protection exerted by physical training against FPI-induced free radical correlated with the immunocontent of the catalytic α1 subunit maintenance. These data suggest that TBI-induced reactive oxygen species (ROS) generation decreases Na+ ,K+ -ATPase activity by decreasing the total number of enzyme molecules, and that physical exercise protects against this effect. Therefore, the effective protection of selected targets, such as Na+ ,K+ -ATPase induced by physical training, supports the idea that physical training may exert prophylactic effects on neuronal cell dysfunction and damage associated with TBI.
Although physical activity and creatine supplementation have been a documented beneficial effect on neurological disorders, its implications for epilepsy are still controversial. Thus, we decided to ...investigate the effects of 6 weeks swimming training, creatine supplementation (300mg/kg; p.o.) or its combination seizures and neurochemical alterations induced by pentylenetetrazol (PTZ). We found that 6 weeks of physical training or creatine supplementation decreased the duration of PTZ-induced seizures in adult male Wistar rats, as measured by cortical and hippocampal electroencephalography and behavioral analysis. Importantly, the combination between physical training and creatine supplementation had additive anticonvulsant effects, since it increased the onset latency for PTZ-induced seizures and was more effective in decrease seizure duration than physical training and creatine supplementation individually. Analysis of selected parameters of oxidative stress and antioxidant defenses in the hippocampus revealed that physical training, creatine supplementation or its combination abrogated the PTZ-elicited increase in levels of thiobarbituric acid-reactive substances (TBARS) and protein carbonylation, as well as decrease in non-protein-thiols content, catalase (CAT) and SOD activities. In addition, this protocol of physical training and creatine supplementation prevented the PTZ-induced decrease in hippocampal Na+,K+-ATPase activity. Altogether, these results suggest that protection elicited physical training and creatine supplementation of selected targets for reactive species-mediated damage decrease of neuronal excitability and consequent oxidative damage elicited by PTZ. In conclusion, the present study shows that physical training, creatine supplementation or its combination attenuated PTZ-induced seizures and oxidative damage in vivo, and provide evidence that combination between creatine supplementation and physical exercise may be a useful strategy in the treatment of convulsive disorders.
Several studies demonstrated the toxicity of aspartame (ASP) and aflatoxin B
(AFB
) 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
co-exposure are rarely addressed. We evaluated if concomitant exposure to AFB
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
(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
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
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
or ASP exposition in the hippocampus. Thus, co-exposure to ASP and AFB
was potentially more toxic because it aggravated behavioral impairments and oxidative status disbalance in comparison to the groups that received only ASP or AFB
. Therefore, our data suggest that those substances caused a disruption in brain homeostasis.
PDF
