Swimming training and caffeine supplementation protects against metabolic syndrome-induced nuclear factor-κB activation and cognitive deficits in rats.

Metabolic syndrome (MS) is a disorder that increasingly affects the world population, mainly because of changes in lifestyle and dietary habits. In this regard, both physical exercise and caffeine are low-cost and easily accessible therapies that separately have shown positive effects against metabolic disorders. Therefore, we hypothesized that physical exercise combined with caffeine could have a synergistic effect in the treatment of MS, risk factors, and cognitive deficits. Animals were divided into 8 groups and received fructose (15% w/v) or vehicle for 10 weeks. Swimming training and caffeine (6 mg/kg) started 4 weeks after fructose administration. Trained animals presented decreased body weight and visceral fat mass and increased soleus weight compared with untrained fructose-treated animals. Caffeine supplementation also prevented the gain of visceral fat mass induced by fructose. Furthermore, both treatments reversed fructose-induced decrease in glucose clearance over time and fructose-induced increase in 4-hydroxynonenal and nuclear factor-κB immunoreactivity. Physical training also improved the lipidic profile in fructose-treated animals (high-density lipoprotein, low-density lipoprotein, and triglycerides), improved short-term, long-term, and localization memory, and reversed the fructose-induced deficit in short-term memory. Physical training also increased nuclear factor erythroid 2-related factor 2 immunoreactivity per se. Considering that physical training and caffeine reversed some of the damages induced by fructose it is plausible to consider these treatments as alternative, nonpharmacological, and low-cost therapies to help reduce MS-associated risk factors; however, combined treatments did not show additive effects as hypothesized.

Protective effect of gamma-oryzanol against manganese-induced toxicity in Drosophila melanogaster.

Manganese (Mn) is an essential element that, in excess, seems to be involved in the development of different neurodegenerative conditions. Gamma-oryzanol (Ory) was previously reported to possess antioxidant and neuroprotective properties. Thus, we conducted this study to test the hypothesis that Ory can also protect flies in an Mn intoxication model. Adult wild-type flies were fed over 10 days with Mn (5 mM) and/or Ory (25 µM). Flies treated with Mn had a decrease in locomotor activity and a higher mortality rate compared to those in controls. Mn-treated flies also had a significant increase in acetylcholinesterase (AChE) activity, in Mn accumulation and in oxidative stress markers. Moreover, flies treated with Mn exhibited a significant decrease in dopamine levels and in tyrosine hydroxylase activity, as well as in mitochondrial and cellular viability. Particularly important, Ory protected against mortality and avoided locomotor and biochemical changes associated with Mn exposure. However, Ory did not prevent the accumulation of Mn. The present results support the notion that Ory effectively attenuates detrimental changes associated with Mn exposure in Drosophila melanogaster, reinforcing its neuroprotective action/potential.

Caffeic acid and caffeine attenuate toxicity associated with malonic or methylmalonic acid exposure in Drosophila melanogaster.

The deficiency in the activity of the mitochondrial enzyme methylmalonyl-CoA mutase (MCM, EC 5.4.99.2) leads to a condition called methylmalonic academia, which is characterised by the accumulation of methylmalonic (MMA), malonic (MA) or other organic acids. Importantly, we have recently found that supplementation with Ilex paraguariensis aqueous extract offered protection against toxicity associated with MMA or MA exposure to Drosophila melanogaster. Of note, caffeic acid (CA) and caffeine (CAF) were the major phytochemicals found in our Ilex paraguariensis crude extract. Therefore, here, we have exploited CA and/or CAF to test the hypothesis that supplementation with the isolated compounds (either alone or combined) could exert a protective effect against MMA or MA-induced toxicity in flies. Therefore, flies were exposed to MA (5 mM) or MMA (5 mM) and concomitantly treated with CA (1.39 µg/mL), CAF (1.27 µg/mL) or CA + CAF for 10 days for survival, and for 4 days for behavioural and biochemical assays. CA, CAF and CA + CAF treatments completely abolished the mortality associated with either MMA or MA exposure. Moreover, CA and CAF, either alone or combined, completely abolished behavioural changes, and completely protect against changes in thiobarbituric acid reactive substances (TBARS) levels, catalase (CAT) activity and MTT reduction ability, associated with MA or MMA exposure. In turn, CAF restored SOD activity in the head of flies exposed to MA or MMA. However, CA and CAF (either alone or combined) significantly decreased acetylcholinesterase (AChE) activity per se, while CAF alone protected from changes in AChE activity (in head tissue) associated with MA or MMA. Finally, CA and/or CAF were able to protect from a decrease in glucose and triglyceride levels associated with both MA and MMA exposures in haemolymph. Together, our data confirm the hypothesis that supplementation with CA and/or CAF offers protection against detrimental changes associated with MMA or MA exposure in flies, being responsible, at least in part, for the protective effect of I. paraguariensis crude extract which was reported previously.

Ilex paraguariensis Attenuates Changes in Mortality, Behavioral and Biochemical Parameters Associated to Methyl Malonate or Malonate Exposure in Drosophila melanogaster.

Methylmalonic acidemia is a genetic disease characterized by accumulation of organic acids, such as methylmalonic (MMA) and malonic (MA) acids. Considering that the accumulation of MMA and MA causes several damages due to oxidative stress, antioxidants are thought to play a pivotal role in preventing deleterious effects associated with exposure to such compounds. Ilex paraguariensis (IP) was used here to test the hypothesis that supplementation with the aqueous extract of this plant could exert protective effect against MMA or MA induced mortality, behavioral and/or biochemical changes in Drosophila melanogaster (DM). Initially, a curve time- and dose-response to MMA (1-10 mM), MA (1-10 mM) and IP (63-500 µM) was performed. Thereafter, flies were concomitantly exposed to MA (5 mM), MMA (5 mM) and/or IP (250 µg/mL) during 15 days for survival assay, and for 48 hs to MA (1 or 5 mM), MMA (1 or 5 mM) and/or IP (250 µg/mL) for subsequent investigations. Both MMA and MA exposure resulted in higher incidence of mortality, a worse performance in the negative geotaxis assay and increased locomotion in open-field test as compared with control group. Furthermore, a marked increase in non-protein thiol (NPSH) and in thiobarbituric acid reactive substances (TBARS) levels, decrease in superoxide dismutase (SOD), catalase and acetylcholinesterase (AChE) activities, and decrease in MTT and resazurin reduction were noted in MMA or MA treated groups. IP treatment offered significant protection against all alterations associated to MMA or MA exposure. This study confirm the hypothesis that supplementation with IP offers protection against changes associated to MMA or MA exposure in DM, due, at least in part, to its antioxidant effect.

Use of Pistia stratiotes for phytoremediation of water resources contaminated by clomazone.

The Pistia stratiotes L. was tested for phytoremediation potential of the compound clomazone in water. Clomazone is a post-emergent herbicide marketed as Gamit®. Five groups with four samples each were evaluated, a low concentration control (LCC: 37.86 mg L-1), low concentration treatment (LCT: 38.16 mg L-1), high concentration control (HCC: 54.71 mg L-1), high concentration treatment (HCT: 54.33 mg L-1), and a plant control group (PCG). Plant resistance to clomazone at determined concentrations and their ability to remove the herbicide from water by HPLC over 24 days were evaluated. The results demonstrate that P. stratiotes has high resistance to clomazone exposure and was able to eliminate up to 90% of the herbicide residues during the experimental period. Under dissipation by P. stratiotes in water, clomazone had a halflife of 19.6 days for in the control treatments, LCC and HCC, and 8.0 days in the treatment groups, LCT and HCT. This study indicates that Pistia stratiotes is an effective phytoremediation agent for the herbicide clomazone in water.

The phytoremediation potential of Plectranthus neochilus on 2,4-dichlorophenoxyacetic acid and the role of antioxidant capacity in herbicide tolerance.

The possible phytoremediation capacity of Plectranthus neochilus (boldo) exposed to the commercial pesticide (Aminol) in soil and water through consecutive extractions (days interval) was evaluated. After the exposure period, tea leaves from the plant were analyzed in terms of the presence of 2,4-D, total antioxidant capacity (DPPH), concentration of total polyphenols and flavonoids for plants exposed to soil and water. In water, 2,4-D remained up to 67% in the 60 days of experiment in the control group, which provided the use of two treatment groups with the plant (one group of plants for 30 days and another group in the remaining 30 days in the same system), thus, a decontamination up to 49% of the 2,4-D was obtained in this system with water. In both experiments (soil and water) the 2,4-D was not detected in tea leaves, the reduction of the antioxidant activity, polyphenols and flavonoids of plants exposed to the herbicide was also observed when compared to the non-exposed plants. In tea - plants in water - it was also possible to quantify the phenolic compounds and it was observed that in the group of plants of the first 30 days there was a decrease in caffeic acid and an increase in coumaric and ferulic acids, compared to the group of plants that were not exposed to 2,4-D. In the remaining 30 days with the new seedlings there was a decrease of the coumaric acid and an increase of the caffeic and ferulic acids.

Peumus boldus (Boldo) Aqueous Extract Present Better Protective Effect than Boldine Against Manganese-Induced Toxicity in D. melanogaster.

The cellular, intracellular and molecular mechanism(s) underlying the toxicity of Mn are still incompletely understood, although several points concerning Mn neurotoxicity have been addressed. Importantly, oxidative changes have been reported to be involved in Mn-induced toxicity. As a consequence, antioxidants are expected to offer protection in Drosophila melanogaster exposed to this metal. So, in this study we evaluated the hypothesis that the aqueous extract of boldo (Peumus boldus), and its alkaloids boldine, could prevent/ameliorate behavioral and oxidative alterations induced by Mn in a D. melanogaster intoxication model. Adult wild-type flies were concomitantly exposed to Mn (3 mM) and boldo aqueous extract (5 mg/mL) or boldine (327.37 µg/mL) in the food during 9 days. Mn-fed flies had a worse performance in the negative geotaxis assay and in the open-field test, as well as a higher incidence of mortality and TBARS levels in head and body, when compared to control group. Boldo aqueous extract was found to reduce the mortality rate of the flies exposed to Mn. In turn, boldine was ineffective against Mn-induced mortality and significantly increases mortality per se. Additionally, Mn-induced locomotors dysfunction were fully ameliorated by boldo crude extract and only partially ameliorated by boldine. Likewise, boldo completely normalize head and body TBARS levels, whereas boldine only partially normalize in body. Finally, we found that flies treated with Mn presented significantly decrease in dopamine levels. Our results suggest that boldo crude extract can exert protective effect against Mn-induced toxicity in D. melanogaster, whereas boldine do not. Moreover, our data confirm the utility of this model to investigate potential therapeutic strategies on movement disorders, such as that caused by Mn.