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This study evaluated the effects of topically applied hydrogels (HG) containing nanoencapsulated indol-3-carbinol (I3C) and its free form in a rat model of skin wounds. Formulations were topically applied twice a day for five days to the wounds. On days 1, 3, and 6, the wound area was measured to verify the % of regression. On the sixth day, the animals were euthanized for the analysis of the inflammatory and oxidative profile in wounds. The nanocapsules (NC) exhibited physicochemical characteristics compatible with this kind of suspension. After five hours of exposure to ultraviolet C, more than 78% of I3C content in the suspensions was still observed. The NC-I3C did not modify the physicochemical characteristics of HG when compared to the HG base. In the in vivo study, an increase in the size of the wound was observed on the 3rd experimental day, which was lower in the treated groups (mainly in HG-NC-I3C) compared to the control. On the 6th day, HG-I3C, HG-NC-B, and HG-NC-I3C showed lower regression of the wound compared to the control. Additionally, HG-NC-I3C exhibited an anti-inflammatory effect (as observed by decreased levels of interleukin-1B and myeloperoxidase), reduced oxidative damage (by decreased reactive species, lipid peroxidation, and protein carbonylation levels), and increased antioxidant defense (by improved catalase activity and vitamin C levels) compared to the control. The current study showed more satisfactory results in the HG-NC-I3C group than in the free form of I3C in decreasing acute inflammation and oxidative damage in wounds.

This study aimed to evaluate the effects of the repeated administration of tramadol subcutaneously on postoperative analgesia, liver, kidneys, and oxidative status in the postoperative period of cats undergoing ovariohysterectomy. Thirty-seven cats were randomly assigned to 5 groups, according to the postoperative analgesic treatment: NaCl 0.9%, GC; tramadol at 2 mg/kg, T2B (q12h) and T2T (q8h); or 4 mg/kg, T4B (q12h) and T4T (q8h). Oxidative status was assessed at baseline, 12 hours and 24 hours after the final administration of tramadol by the activity of superoxide dismutase (SOD), catalase (CAT), myeloperoxidase (MPO), butyrylcholinesterase (BuChE), and lipoperoxidation (MDA). Total blood count, serum biochemistry and urinalysis were compared between baseline and 12 hours posttramadol. Postoperative pain was evaluated by applying the Glasgow Feline Composite Measure Pain Scale at baseline, 3 (T3), 6 (T6), 8 (T8), 12 (T12), 24 (T24) e 36 (T36) hours after extubation. No side effects were observed. Tramadol increased SOD activity while CAT varied among groups in all time points but not over time. MDA levels increased from baseline to 12 hours in all groups but T4T. MPO activity decreased from baseline to 24 hours in some groups, including GC. Creatinine and phosphatase alkaline decreased in T2T, T4B, and T4T at 12 hours. Higher pain scores were observed from T3 to T8, except for GC. Rescue analgesia was administered only at T3. No difference in pain scores was observed from T8 onwards. Based on the findings, it is suggested that tramadol at 2 mg/kg every 8 hours is recommended for postoperative analgesia of cats undergoing ovariohysterectomy., Competing Interests: Declaration of Competing Interest None of the authors of this article has a financial or personal relationship with other people or organizations that may influence the content of the article, declaring any potential conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Psychostimulant drugs addiction is a chronic public health problem and individuals remain susceptible to relapses increasing public expenses even after withdrawal and treatment. Our research group has focused on finding new therapies to be employed in drug addiction treatment, suggesting the physical exercise as a promising tool. This way, it is necessary to know the mechanisms involved in the beneficial influences of physical exercise observing the pathway that could be explored in drug addiction treatment. Male Wistar rats were conditioned with amphetamine (AMPH) following the conditioned place preference (CPP) protocol and subsequently submitted to swimming for 5 weeks (1 h per day, 5 days per week). Half of the animals were injected with Naloxone (0.3 mg/mL/kg body weight, i.p.) 5 min prior each physical exercise day. After AMPH-CPP re-exposure, our outcomes showed that physical exercise, in addition to minimizing the relapse behavior in the CPP, it increased D1R, D2R and DAT in the Ventral Tegmental Area (VTA), but not in the Nucleus accumbens (NAc). Interestingly, while naloxone inhibited the partial beneficial influence of the exercise on drug-relapse behavior, exercise-induced changes in the dopaminergic system were not observed in the group administered with naloxone as well. Based on these evidences, besides reinforcing the beneficial influence of the physical exercise on AMPH-induced drug addiction, we propose the involvement of endogenous opioid system activation, not as a single one, but as a possible mechanism of action resulting from the physical activity practice, thus characterizing an important therapeutic approach, which may contribute to drug withdrawal consequently preventing relapse., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Addiction is a devastating worldwide disorder that requires effective and innovative therapies. Physical exercise could be useful in addiction treatment because it shares a common neural circuit with addictive drugs. Based on this, molecular adaptations consequent to time of exercise in opioid exposed animals were evaluated. Rats were designed as sedentary (SED) or exercised (EXE). This last group was separated to perform three different periods of swimming: short-term (S-EXE), medium-term (M-EXE) and long-term (L-EXE) for 14, 28 and 42 days, respectively. On the last exercising week, one-half of the animals from SED and all animals from S-, M- and l-EXE were concomitantly exposed to morphine-conditioned place preference (CPP) paradigm and y-maze task for behavioral assessments followed by molecular assays in both Nucleus accumbens (NAc) and hippocampus. Between SED groups, morphine conditioning showed drug-CPP and increased dopamine transporter (DAT), dopamine receptor type-1 (D1R), type-2 (D2R) and glucocorticoid receptor (GR) in both brain areas in relation to saline group. Besides the small morphine-CPP in relation to SED group, all periods decreased DAT, D1R, and GR immunoreactivity in NAc, DAT and D1R in hippocampus, while D2R in both brain areas and GR in hippocampus were primarily decreased by L-EXE. Our findings show that even a short-term exercise modifies behaviors related to drug withdrawal, changing DA targets and GR, which are closely linked to addiction. Therefore, our outcomes involving physical exercise are interesting to perform a possible clinical trial, thus expanding the knowledge about drug addiction., (Copyright © 2019 Elsevier B.V. and ECNP. All rights reserved.)

Introduction: Ketamine (KET) is an anesthetic agent widely used in human and veterinary medicine. According to studies, KET is associated to direct neutorotoxic damages due to its capacity to induce oxidative stress. Because of the free radical generation in the organism and its relation with diseases' development, there is a growing interest to study antioxidant molecules, such as gallic acid (GA), a natural phenolic compound., Aim: Evaluate the GA antioxidant potential for the prevention of oxidative damage in the brain and liver tissue of rats exposed to acute KET administration., Material and Methods: 32 Wistar male rats received GA (by gavage, 13.5 mg/kg) for three consecutive days, 24 h after the last GA dose, animals were anesthetized with KET (50 mg/kg, i.m.). All animals were euthanized by decapitation 60 min after KET administration. The liver, brain cortex and hippocampus were removed and homogenized for biochemical analysis., Results: In brain cortex, KET increased reactive species (RS) generation, protein carbonyls (PC) levels and reduced non-protein thiols (NPSH) levels, while GA pre-treatment reduced PC and increased NPSH levels. KET increased PC and decreased NPSH levels in the hippocampus, and GA reduced PC and NPSH levels. In the liver, no difference was observed in the RS generation, while KET induced and increase of PC levels and decreased NPSH levels, while GA pre-treatment prevented it., Conclusion: GA administration can prevent oxidative damage caused by acute KET administration and minimize its noxious effects. Further studies are needed to evidence GA antioxidant properties regarding KET chronic use., (Copyright © 2019. Published by Elsevier B.V.)

Amphetamine (AMPH) and its derivatives are addictive drugs used to promote and enhance alertness, motivation, willingness, courage and wellbeing. However, their chronic use is related to memory loss, emotional instability, insomnia, psychosis and paranoia. In the last decades, modern society has included processed foods, rich in trans fatty acids (TFA), in their diet, what has been related to several health problems including increased AMPH preference and self-administration. In this scenario, physical activity appears to be useful to attenuate rewarding symptoms related to addictive drugs mainly by affecting brain neuroplasticity and neurotransmission. The current study has been developed to assess the influence of physical activity on addiction parameters of rats exposed to AMPH which were previously supplemented with hydrogenated vegetable fat (HVF), rich in TFA. After six weeks of HVF or soybean oil (SO, control group) supplementation, adult rats were conditioned with d,l-AMPH or vehicle for 14 days. Then, half of each experimental group was submitted to physical activity in treadmill running sessions (60min/day, 5 days/week) for 5 weeks. Animals were re-conditioned with AMPH or vehicle for 3 more days, to observe drug relapse. Locomotor activity and anxiety-like symptoms were observed 24h after the last AMPH reconditioning, and fatty acids composition was quantified in the ventral tegmental area, striatum and prefrontal cortex. All animals showed AMPH preference, but only SO sedentary showed drug relapse. No differences were observed in locomotor activity among groups, while HVF-supplemented group showed decreased exploration per se, and physical activity prevented this. Moreover, AMPH-HVF group showed increased anxiety-like symptoms, which were prevented by physical activity. These results indicate that HVF supplementation modifies AMPH addiction, whereas regular physical activity could be protective against both AMPH and TFA damages., (Copyright © 2017 Elsevier Inc. All rights reserved.)

We evaluated the influence of dietary fats on ultraviolet radiation (UVR)-induced oxidative damage in skin of rats. Animals from two consecutive generations born of dams supplemented with fats during pregnancy and breastfeeding were maintained in the same supplementation: soybean-oil (SO, rich in n-6 FA, control group), fish-oil (FO, rich in n-3 FA) or hydrogenated-vegetable-fat (HVF, rich in TFA). At 90 days of age, half the animals from the 2nd generation were exposed to UVR (0.25 J/cm(2)) 3×/week for 12 weeks. The FO group presented higher incorporation of n-3 FA in dorsal skin, while the HVF group incorporated TFA. Biochemical changes per se were observed in skin of the HVF group: greater generation of reactive oxygen species (ROS), lower mitochondrial integrity and increased Na(+)K(+)-ATPase activity. UVR exposure increased skin wrinkles scores and ROS generation and decreased mitochondrial integrity and reduced-glutathione levels in the HVF group. In FO, UVR exposure was associated with smaller skin thickness and reduced levels of protein-carbonyl, together with increased catalase activity and preserved Na(+)K(+)-ATPase function. In conclusion, while FO may be protective, trans fat may be harmful to skin health by making it more vulnerable to UVR injury and thus more prone to develop photoaging and skin cancer., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The aim of this study was to compare the effects of manganese (Mn) on silver catfish exposed to different levels of dissolved oxygen. Silver catfish (Rhamdia quelen) were exposed to increasing concentrations of Mn (4.2, 8.4 or 16.2mgL(-1)) under either normoxia (100 percent saturation) or moderate hypoxia (51.87 percent saturation) for 15 days. Under normoxia, Mn exposure increased lipid peroxidation (LP) in brain and kidney; it increased gluthatione (GSH) levels in brain and decreased catalase (CAT) activity in both tissues. Moderate hypoxia was able to prevent Mn-induced LP in brain and to reduce this oxidative parameter in kidney; GSH level was increased in brain, while CAT activity was reduced in both tissues. Activity of isolated mitochondria of liver and gills was reduced by Mn exposure under both levels of dissolved oxygen, but this effect was more prominent in normoxia. As expected, liver, kidney and gills showed an increase of Mn accumulation according to waterborne levels, and these parameters presented positive relationship. The highest waterborne Mn (8.4 and 16.2mgL(-1)) resulted in greater accumulation under normoxia, indicating that moderate hypoxia can stimulate mechanisms capable of reducing Mn accumulation in tissues (though not in blood). Moderate hypoxia can be considered a stress factor and Mn an aquatic anthropogenic contaminant. Therefore we hypothesized that these two conditions together are able to invoke defense mechanisms in juvenile silver catfish, acting in a compensatory form, which may be related to adaptation and/or hormesis., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Here we evaluated the influence of physical exercise on behavior parameters and enzymatic status of rats supplemented with different dietary fatty acids (FA). Male Wistar rats fed diets enriched with soybean oil (SO), lard (L), or hydrogenated vegetable fat (HVF) for 48 weeks were submitted to swimming (30 min/d, five times per week) for 90 days. Dietary FA per se did not cause anxiety-like symptoms in the animals, but after physical exercise, SO group showed a better behavioral performance than L and the HVF groups in elevated plus maze (EPM). In Barnes maze, HVF group showed impaired memory acquisition as compared to L group, and exercise reversed this effect. SO-fed rats showed an improvement in memory acquisition after 1 day of training, whereas lard caused an improvement of memory only from day 4. HVF-fed rats showed no improvement of memory acquisition, but this effect was reversed by exercise in all training days. A lower activity of the Na(+)K(+)-ATPase in brain cortex of rats fed lard and HVF was observed, and this effect was maintained after exercise. Similarly, the HVF diet was related to lower activity of hippocampal Na(+)K(+)-ATPase, and exercise reduced activity of this enzyme in the SO and L groups. Our findings show influences of dietary FA on memory acquisition, whereas regular exercise improved this function and was beneficial on anxiety-like symptoms. As FA are present in neuronal membrane phospholipids and play a critical role in brain function, our results suggest that low incorporation of trans FA in neuronal membranes may act on cortical and hippocampal Na(+)K(+)-ATPase activity, but this change appears to be unrelated to the behavioral parameters primarily harmed by consumption of trans and less so by saturated FA, which were reversed by exercise., (Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.)

In the last decades, foods rich in omega-3 (ω-3) fatty acids (FA) have been replaced by omega-6 (ω-6) and trans FA, which are found in processed foods. The influence of ω-6 (soybean oil--SO), trans (hydrogenated vegetable fat--HVF) and ω-3 (fish oil--FO) fatty acids on locomotor and oxidative stress (OS) parameters were studied in an animal model of mania. Rats orally fed with SO, HVF and FO for 8 weeks received daily injections of amphetamine (AMPH--4 mg/kg/mL-ip) for the last week of oral supplementation. HVF induced hyperactivity, increased the protein carbonyl levels in the cortex and decreased the mitochondrial viability in cortex and striatum. AMPH-treatment increased the locomotion and decreased the mitochondrial viability in all groups, but its neurotoxicity was higher in the HVF group. Similarly, AMPH administration increased the protein carbonyl levels in striatum and cortex of HVF-supplemented rats. AMPH reduced the vitamin-C plasmatic levels of SO and HVF-fed rats, whereas no change was observed in the FO group. Our findings suggest that trans fatty acids increased the oxidative damage per se and exacerbated the AMPH-induced effects. The impact of trans fatty acids consumption on neuronal diseases and its consequences in brain functions must be further evaluated., (Copyright © 2010 Elsevier Inc. All rights reserved.)