Antibiotic activity of Plectranthus ornatus Codd., a Traditional Medicinal Plant.

The dichloromethane extract of Plectranthus ornatus Codd., a tradicional medicinal plant, showed antibiotic activity with minimum inhibitory concentration (MIC) values of 0.4 mg.mL-1 and 100 percent of biofilm inhibition against Staphylococcus aureus strains isolated from animals with mastitis infections. Based on these antibacterial activities, in addition to ethnopharmacological reports from healing men and farmers in Brazil, an herbal soap was produced from this active extract and was tested both in vitro and in vivo. In vivo assays conducted on these herbal soaps led to results similar to those previously conducted with the active extract. These results indicated the great potential of this plant for use as an excipient by preparing herbal antibacterial soaps as an alternative veterinary medicine aimed at controlling bovine mastitis infections on small Brazilian farms.

Evidence of oxidative stress in brain and liver of young rats submitted to experimental galactosemia.

Galactosemia is a disorder of galactose metabolism, leading to the accumulation of this carbohydrate. Galactosemic patients present brain and liver damage. For evaluated oxidative stress, 30-day-old males Wistar rats were divided into two groups: galactose group, that received a single injection of this carbohydrate (5 µmol/g), and control group, that received saline 0.9 % in the same conditions. One, twelve or twenty-four hours after the administration, animals were euthanized and cerebral cortex, cerebellum, and liver were isolated. After one hour, it was found a significant increase in TBA-RS levels, nitrate and nitrite and protein carbonyl contents in cerebral cortex, as well as protein carbonyl content in the cerebellum and in hepatic level of TBA-RS, and a significant decrease in nitrate and nitrite contents in cerebellum. TBA-RS levels were also found increased in all studied tissues, as well as nitrate and nitrite contents in cerebral cortex and cerebellum, that also present increased protein carbonyl content and impairments in the activity of antioxidant enzymes of rats euthanized at twelve hours. Finally, animals euthanized after twenty-four hours present an increase of TBA-RS levels in studied tissues, as well as the protein carbonyl content in cerebellum and liver. These animals also present an increased nitrate and nitrite content and impairment of antioxidant enzymes activities. Taken together, our data suggest that acute galactose administration impairs redox homeostasis in brain and liver of rats.

Neutrotoxic effects of fructose administration in rat brain: implications for fructosemia.

Fructose accumulates in tissue and body fluids of patients affected by hereditary fructose intolerance (HFI), a disorder caused by the deficiency of aldolase B. We investigated the effect of acute fructose administration on the biochemical profile and on the activities of the Krebs cycle enzymes in the cerebral cortex of young rats. Rats received a subcutaneous injection of NaCl (0.9 %; control group) or fructose solution (5 µmol/g; treated group). Twelve or 24 h after the administration, the animals were euthanized and the cerebral cortices were isolated. Peripheral blood (to obtain the serum) and cerebral spinal fluid (CSF) from the animals were also collected. It was observed that albumin levels were decreased and cholesterol levels were increased in CSF of animals 12 h after the administration of fructose. In addition, serum lactate levels were increased 12 h after the administration, as compared to control group. Furthermore, malate dehydrogenase activity was increased in cerebral cortex from treated group 24 h after the administration of this carbohydrate. Herein we demonstrate that fructose administration alters biochemical parameters in CSF and serum and bioenergetics parameters in the cerebral cortex. These findings indicate a possible role of fructose on brain alterations found in HFI patients.

Pharmacokinetic, Hemostatic, and Anticancer Properties of a Low-Anticoagulant Bovine Heparin.

Heparin is a centennial anticoagulant drug broadly employed for treatment and prophylaxis of thromboembolic conditions. Although unfractionated heparin (UFH) has already been shown to have remarkable pharmacological potential for treating a variety of diseases unrelated with thromboembolism, including cancer, atherosclerosis, inflammation, and virus infections, its high anticoagulant potency makes the doses necessary to exert non-hemostatic effects unsafe due to an elevated bleeding risk. Our group recently developed a new low-anticoagulant bovine heparin (LABH) bearing the same disaccharide building blocks of the UFH gold standard sourced from porcine mucosa (HPI) but with anticoagulant potency approximately 85% lower (approximately 25 and 180 Heparin International Units [IU]/mg). In the present work, we investigated the pharmacokinetics profile, bleeding potential, and anticancer properties of LABH administered subcutaneous into mice. LABH showed pharmacokinetics profile similar to HPI but different from the low-molecular weight heparin (LMWH) enoxaparin and diminished bleeding potential, even at high doses. Subcutaneous treatment with LABH delays the early progression of Lewis lung carcinoma, improves survival, and brings beneficial health outcomes to the mice, without the advent of adverse effects (hemorrhage/mortality) seen in the animals treated with HPI. These results demonstrate that LABH is a promising candidate for prospecting new therapeutic uses for UFH.

Phenolic Compounds of Red Wine Aglianico del Vulture Modulate the Functional Activity of Macrophages via Inhibition of NF-κB and the Citrate Pathway.

Phenolic compounds of red wine powder (RWP) extracted from the Italian red wine Aglianico del Vulture have been investigated for the potential immunomodulatory and anti-inflammatory capacity on human macrophages. These compounds reduce the secretion of IL-1ß, IL-6, and TNF-α proinflammatory cytokines and increase the release of IL-10 anti-inflammatory cytokine induced by lipopolysaccharide (LPS). In addition, RWP restores Annexin A1 levels, thus involving activation of proresolutive pathways. Noteworthy, RWP lowers NF-κB protein levels, promoter activity, and nuclear translocation. As a consequence of NF-κB inhibition, reduced promoter activities of SLC25A1-encoding the mitochondrial citrate carrier (CIC)-and ATP citrate lyase (ACLY) metabolic genes have been observed. CIC, ACLY, and citrate are components of the citrate pathway: in LPS-activated macrophages, the mitochondrial citrate is exported by CIC into the cytosol where it is cleaved by ACLY in oxaloacetate and acetyl-CoA, precursors for ROS, NO·, and PGE2 inflammatory mediators. We identify the citrate pathway as a RWP target in carrying out its anti-inflammatory activity since RWP reduces CIC and ACLY protein levels, ACLY enzymatic activity, the cytosolic citrate concentration, and in turn ROS, NO·, PGE2, and histone acetylation levels. Overall findings suggest that RWP potentially restores macrophage homeostasis by suppressing inflammatory pathways and activating proresolutive processes.

Vitamin A supplementation induces oxidative stress and decreases the immunocontent of catalase and superoxide dismutase in rat lungs.

Lungs require an adequate supply of vitamin A for normal embryonic development, postnatal maturation, and maintenance and repair during adult life. However, recent intervention studies revealed that supplementation with retinoids resulted in a higher incidence of lung cancer, although the mechanisms underlying this effect are still unknown. Here, the authors studied the effect of vitamin A supplementation on oxidative stress parameters in lungs of Wistar rats. Vitamin A supplementation either at therapeutic (1000 and 2500 IU/kg) or excessive (4500 and 9000 IU/kg) doses for 28 days induced lipid peroxidation, protein carbonylation, and oxidation of protein thiol groups, as well as change in catalase (EC 1.11.1.6; CAT) and superoxide dismutase (EC 1.15.1.1, SOD) activities and immunocontents. These results altogether suggest that vitamin A supplementation causes significant changes in redox balance the free radical status in lungs, which are frequently associated to severe lung dysfunction.

Protective effects of purple grape juice on carbon tetrachloride-induced oxidative stress in brains of adult Wistar rats.

The antioxidant properties of purple grape juice, organic and conventional, in brain tissues are not well known. In this study our objective was to evaluate the antioxidant activity in substantia nigra and striatum of rats chronically treated with organic or conventional purple grape juice and to correlate the results obtained with the polyphenol content (total polyphenolic content, resveratrol, and anthocyanins [malvidin, delphinidin, peonidin, and cyanidin]). We observed that CCl(4) damage decreased significantly in the grape juice-treated groups when compared with the control group. In the grape juice-treated groups we further observed a decrease of lipid (thiobarbituric acid-reactive substances assay) and protein (carbonyl) peroxidation, as well as a significant antioxidant protection through the increase of enzyme activity. Antioxidant activities were significantly correlated with polyphenol content. These findings demonstrated that both grape juices have potent antioxidant properties and these activities could be at least attributed to the high phenolic content present in these juices.

Intake of purple grape juice as a hepatoprotective agent in Wistar rats.

Grape juice is a source of polyphenols, as catechin, anthocyanidins, resveratrol, and others. Some health benefits have been attributed to these compounds (e.g., antioxidant and antitumorigenic properties). In this study, we investigated the possible antioxidant activity of two different grape juices: organic purple grape juice and conventional purple grape juice. The antioxidant activity of both grape juices was evaluated by an animal model of three groups: control and organic and conventional juices. After 30 days, all animals were sacrificed, and blood and liver were collected to evaluate lipid peroxidation level (thiobarbituric acid-reactive substances [TBARS] assay), protein oxidative level (carbonyl assay), and catalase (CAT) and superoxide dismutase (SOD) activities. The group treated with organic grape juice showed the highest SOD and CAT activities in both plasma and liver when compared with the conventional and control groups (P < .05). In plasma, we observed a positive correlation among SOD and CAT activities, resveratrol, and all anthocyanin contents, suggesting that these polyphenols may be, at least in part, responsible for this increased antioxidant defense. The grape juices were capable of reducing carbonyl and lipid peroxidation levels in plasma and liver. However, in plasma, the organic group showed lower carbonyl and TBARS levels when compared to the conventional grape juice group (P < .05). Our findings suggest that the intake of purple grape juice, especially of organic juice, induces a better antioxidant capacity when compared to conventional juice and that this may be an important issue for further investigations in the area of biochemical functional foods.

Increased susceptibility of mitochondria isolated from frontal cortex and hippocampus of vitamin A-treated rats to non-aggregated amyloid-ß peptides 1-40 and 1-42.

OBJECTIVE: Vitamin A is a redox-active molecule and its inadvertent utilisation as a preventive therapy against ageing or neurodegeneration has become a harmful habit among humans at different ages. Mitochondrial dysfunction and redox impairment may be induced by vitamin A supplementation experimentally. Nonetheless, it is still not clear by which mechanisms vitamin A elicits such effects. Then, we performed this investigation to analyse whether mitochondria isolated from frontal cortex and hippocampus of vitamin A-treated rats are more sensitive to a challenge with amyloid-ß (Aß) peptides 1-40 or 1-42. METHODS: Adult Wistar rats received vitamin A at 1000-9000 IU/kg/day orally for 28 days. Then, mitochondria were isolated and the challenge with Aß peptides 1-40 or 1-42 (at 0.2 or 0.1 µM, respectively) for 10 min was carried out before mitochondrial electron transfer chain enzyme activity, superoxide anion radical (O2 -•) production and 3-nitrotyrosine content quantification. RESULTS: Mitochondria obtained from vitamin A-treated rats are more sensitive to Aß peptides 1-40 or 1-42 than mitochondria isolated from the control group, as decreased mitochondrial complex enzyme activity and increased O2 -• production and 3-nitrotyrosine content were observed in incubated mitochondria isolated from vitamin A-treated rats. CONCLUSION: These data suggest that oral intake of vitamin A at clinical doses increases the susceptibility of mitochondria to a neurotoxic agent even at low concentrations.

Antibiotic activity of Plectranthus ornatus Codd, a Traditional Medicinal Plant

ABSTRACT The dichloromethane extract of Plectranthus ornatus Codd., a tradicional medicinal plant, showed antibiotic activity with minimum inhibitory concentration (MIC) values of 0.4 mg.mL-1 and 100 percent of biofilm inhibition against Staphylococcus aureus strains isolated from animals with mastitis infections. Based on these antibacterial activities, in addition to ethnopharmacological reports from healing men and farmers in Brazil, an herbal soap was produced from this active extract and was tested both in vitro and in vivo. In vivo assays conducted on these herbal soaps led to results similar to those previously conducted with the active extract. These results indicated the great potential of this plant for use as an excipient by preparing herbal antibacterial soaps as an alternative veterinary medicine aimed at controlling bovine mastitis infections on small Brazilian farms.

Scavenging and antioxidant potential of physiological taurine concentrations against different reactive oxygen/nitrogen species.

While several studies have been conducted on the antioxidant properties of the beta-amino acid taurine, these studies all used concentrations lower than what is found physiologically. This study investigates the scavenging and antioxidant properties of physiological taurine concentrations against different reactive species. No reactivity between taurine and hydrogen peroxide was found; however, taurine exhibited significant scavenging potential against peroxyl radical, nitric oxide, and superoxide donors. This study also evaluated if taurine was able to minimize the in vitro CuZn-superoxide dismutase damage (SOD) induced by peroxynitrite. Taurine prevented both the formation of nitrotyrosine adducts and the decrease in SOD activity caused by peroxynitrite. In addition, taurine prevented the ex vivo damage caused by tert-butyl hydroperoxide in rat liver slices. These experimental data show that taurine, at different physiological concentrations efficiently scavenges many reactive oxygen and nitrogen species. This finding supports the hypothesis that the antioxidant properties of taurine may be critical for the maintenance of cellular functions, and it suggests a more important function of taurine that requires further investigation.

Impairment of the mitochondrial electron transport chain due to sleep deprivation in mice.

It has been demonstrated that sleep deprivation is associated with altered expression of genes related to metabolic processes, response to stress and inflammation, circadian sleep/wake cycles, regulation of cell proliferation and various signaling pathways. However, the molecular mechanisms underlying these changes remain poorly understood. Thus, the present study aims to characterize the function of the mitochondrial electron transport chain in the brain using an animal model of paradoxical sleep deprivation (PSD). The question of whether sleep recovery (rebound) can reverse changes found after PSD is also addressed. Adult male inbred C57BL/6J mice were randomly distributed into three groups: home-cage control, PSD and sleep rebound groups. The PSD and rebound groups were subjected to PSD for 72 h. After this sleep deprivation period, the rebound group was returned to its home cage and allowed to sleep in an undisturbed and spontaneous fashion for 24h. The mitochondrial complex I-III, complex II, succinate dehydrogenase and complex II-III activities were then measured by spectrophotometric methods in sub-mitochondrial particles extracted from the prefrontal cortex, hippocampus, striatum and hypothalamus. Our results showed a significant decrease in the activity of complex I-III in the PSD and rebound groups as compared to the control group. The complex II and II-III activity were particularly decreased in the hypothalamus of the sleep rebound group. These results are consistent with the involvement of sleep in energy metabolism and corroborate previous experiments demonstrating the importance of the hypothalamus in sleep regulation.

Evaluation of redox and bioenergetics states in the liver of vitamin A-treated rats.

Vitamin A is normally stored in the mammalian liver and is physiologically released depending on the need of the organism for the vitamin. However, there is a compelling evidence showing that even the liver is affected by conditions of high vitamin A intake. Based on these previously reported findings showing negative effects of vitamin A on mammalian tissues, we have investigated the effects of a supplementation with vitamin A at clinical doses (1000-9000 IU/kg day(-1)) on some rat liver parameters. We have analyzed hepatic redox environment, as well as the activity of the mitochondrial electron transfer chain in vitamin A-treated rats. Additionally, activity of the detoxifying enzyme glutathione S-transferase was checked. Also, caspase-3 and caspase-8 and tumor necrosis factor-alpha levels were quantified to assess either cell death or inflammation effects of vitamin A on rat liver. We found increased free radical production and, consequently, increased oxidative damage in biomolecules in the liver of vitamin A-treated rats. Interestingly, we found increased mitochondrial electron transfer chain activity, as well as glutathione-S-transferase enzyme activity. Neither caspases activity, nor tumor necrosis factor-alpha levels change in this experimental model. Our results suggest a pro-oxidant, but not pro-inflammatory effect of vitamin A on rat liver.

WITHDRAWN: Impairment of the mitochondrial electron transport chain due to sleep deprivation in mice.

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Imbalance in SOD/CAT activities in rat skeletal muscles submitted to treadmill training exercise.

The association between physical exercise and oxidative damage in the skeletal musculature has been the focus of many studies in literature, but the balance between superoxide dismutase and catalase activities and its relation to oxidative damage is not well established. Thus, the aim of the present study was to investigate the association between regular treadmill physical exercise, oxidative damage and antioxidant defenses in skeletal muscle of rats. Fifteen male Wistar rats (8-12 months) were randomly separated into two groups (trained n=9 and untrained n=6). Trained rats were treadmill-trained for 12 weeks in progressive exercise (velocity, time, and inclination). Training program consisted in a progressive exercise (10 m/min without inclination for 10 min/day). After 1 week the speed, time and inclination were gradually increased until 17 m/min at 10% for 50 min/day. After the training period animals were killed, and gastrocnemius and quadriceps were surgically removed to the determination of biochemical parameters. Lipid peroxidation, protein oxidative damage, catalase, superoxide dismutase and citrate synthase activities, and muscular glycogen content were measured in the isolated muscles. We demonstrated that there is a different modulation of CAT and SOD in skeletal muscle in trained rats when compared to untrained rats (increased SOD/CAT ratio). TBARS levels were significantly decreased and, in contrast, a significant increase in protein carbonylation was observed. These results suggest a non-described adaptation of skeletal muscle against exercise-induced oxidative stress.

Pathogenicity and histopathological observations of commercial broilerchicks experimentally infected with isolates of Eimeria tenella,E. acervulina and E. maxima / Patogenicidade e observações histopatológicas de frangos de corte infectados experimentalmente com isolados de Eimeria tenella, E. acervulina e E. maxima

Cooccidiosis is one of the most important causes of economic losses within the poultry industry. The objective of this study was to evaluate the pathogenicity of E. tenella, E. acervulina, and E. maximastrains in commercial broilers chicks. Thirty nine commercial one day old broiler chicks, unvaccinatedagainst coccidiosis, were used during this experiment. At day 14, chickens of G1 (n=10), G2 (n=10) andG3 (n=10) were infected with 2 x 104 sporulated oocysts of E. tenella, E. acervulina, and E. maxima respectively; G4 (n=9) served as the uninfected control group. All birds were sacrificed with 21 day old(seven days after infection). The prepatent period (PPP) for G1 and G3 was seven days, however, E.acervulina (G2) had a PPP of five days. No statistical differences were observed when the averageweight gain (G1=182.7±63.4; G2=145.2±51.0; G3=183.3±56.8; and G4=211.5±89.0, p>0.10) of the evaluatedgroups was compared. Average of lesion scores were determined G1 (1.3±0.48, scores 1(n=7) and 2(n=3)),G2 (0.4±0.52, scores 0(n=6), 1(n=4)), and G3 (1.1±0.99, scores 0(n=4), 1(n=1) and 2(n=5)). Chickens fromthe infected groups (G1, G2 and G4) did not demonstrate a lesion score above 2. The histopathological lesions induced by these strains were consistent with those described for infection by Eimeria spp.

A coccidiose aviária é uma das principais causas de perdas econômicas na avicultura de corte. Considerando isto, o presente trabalho teve como objetivo avaliar a patogenicidade de cepas de Eimeria tenella, E. acervulina e E. maxima em aves de corte de uso comercial. Para tanto, 39 pintinhos tipo corte com um dia de idade, não vacinados para coccidiose, foram utilizados neste experimento. No 14° dia do experimento, os grupos foram infectadas com 2 x 104 oocistos esporulados de E. tenella (G1, n=10), E. acervulina (G2, n=10) e E. maxima (G3, n=10). Um grupo com nove aves (G4) serviu como grupo controle não infectado. Todos os animais foram eutanasiados com 21 dias de idade (7 dias pós-infecção). O período pré-patente (PPP) nos grupos G1 e G3 foi de sete dias, quando excretaram 52.000 e 8.000 oocistos/g de fezes, respectivamente; no entanto, o grupo infectado com E. acervulina (G2) apresentou um PPP de 5 dias. Não foram verificadas diferenças estatísticas quanto ao ganho de peso vivo (G1=182.7±63.4; G2=145.2±51.0; G3=183.3±56.8; e G4=211.5±89.0, p>0.10). Os escores de lesão foram determinados para cada grupo G1(1.3±0.48, escores 1(n=7) e 2(n=3)), G2 (0.4±0.52, escores 0(n=6), 1(n=4)), e G3 (1.1±0.99, escores 0(n=4), 1(n=1) e 2(n=5)). Considerando todos os grupos infectados (G1, G2 e G4) nenhum mostrou escore maior que 2. As lesões histopatológicas induzidas por estas cepas foram compatíveis com aquelas descritas por infecção por Eimeria spp.