Gastroprotective activity of the resin from Virola oleifera.

CONTEXT: The resin from the trunk wood of Virola oleifera (Schott) A. C. Smith (Myristicaceae) is used in folk medicine to hasten wound repair and to treat pain and inflammatory conditions, and our previous report indicated the anti-oxidative properties in other oxidative stress model. OBJECTIVE: To investigate the protective effects of resin from V. oleifera in two experimental models of gastric ulcer oxidative-stress dependent. MATERIALS AND METHODS: Plant material was collected and the resin was subjected to partitioning with organic solvents. The buthanol fraction was subjected to chromatographic and spectrometric methods for isolation and structural elucidation. The resin was quantified for polyphenols and flavonoids by colorimetric methods. Furthermore, the antioxidant activity of resin was determined by three different methods. The ulcers were induced acutely in Swiss male mice with ethanol/HCl and indomethacin using single-doses of 10 and 100 mg/kg. The gastroprotection of the experimental groups was comparable to reference control lansoprazole (3 mg/kg). RESULTS: The high content of polyphenols (∼82%) and the presence of epicatechin and eriodictyol were determined. The LD50 was estimated at 2500 mg/kg. At minimum (10 mg/kg) and maximum (100 mg/kg) dosage of resin, both in ethanol/HCl as indomethacin ulcer induction models demonstrate reduction of lesions (minimum: ∼97% and ∼66%; maximum: ∼95% and ∼59%). DISCUSSION: The gastroprotection might be related to tannins, phenolic acids and flavonoids present in the resin by antioxidant properties. CONCLUSIONS: The results indicate that this resin has gastroprotective activity probably associated with the presence of phenolic antioxidant substances.

Coadjuvants in the Diabetic Complications: Nutraceuticals and Drugs with Pleiotropic Effects.

Because diabetes mellitus (DM) is a multifactorial metabolic disease, its prevention and treatment has been a constant challenge for basic and clinical investigators focused on translating their discoveries into clinical treatment of this complex disorder. In this review, we highlight recent experimental and clinical evidences of potential coadjuvants in the management of DM, such as polyphenols (quercetin, resveratrol and silymarin), cultured probiotic microorganisms and drugs acting through direct/indirect or pleiotropic effects on glycemic control in DM. Among several options, we highlight new promising therapeutic coadjuvants, including chemical scavengers, the probiotic kefir and the phosphodiesterase 5 inhibitors, which besides the reduction of hyperglycemia and ameliorate insulin resistance, they reduce oxidative stress and improve endothelial dysfunction in the systemic vascular circulation. In the near future, experimental studies are expected to clear the intracellular pathways involving coadjuvants. The design of clinical trials may also contribute to new strategies with coadjuvants against the harmful effects of diabetic complications.

Oxidative Stress and Dementia in Alzheimer's Patients: Effects of Synbiotic Supplementation.

BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia in elderly patients. Recently, several studies have shown that inflammation and oxidative stress precede the cardinal neuropathological manifestations of AD. In view of the proven antioxidant effects of probiotics, we proposed that continuous dietary supplementation with milk fermented with kefir grains might improve cognitive and metabolic and/or cellular disorders in the AD patients. METHODS: This study was designed as an uncontrolled clinical investigation to test the effects of probiotic-fermented milk supplementation (2 mL/kg/daily) for 90 days in AD patients exhibiting cognitive deficit. Cognitive assessment, cytokine expression, systemic oxidative stress levels, and blood cell damage biomarkers were evaluated before (T0) and after (T90) kefir synbiotic supplementation. RESULTS: When the patients were challenged to solve 8 classical tests, the majority exhibit a marked improvement in memory, visual-spatial/abstraction abilities, and executive/language functions. At the end of the treatment, the cytometric analysis showed an absolute/relative decrease in several cytokine markers of inflammation and oxidative stress markers (·O2 -, H2O2, and ONOO-, ~30%) accompanied by an increase in NO bioavailability (100%). In agreement with the above findings by using the same technique, we observed in a similar magnitude an improvement of serum protein oxidation, mitochondrial dysfunction, DNA damage/repair, and apoptosis. CONCLUSION: In conclusion, we demonstrated that kefir improves cognitive deficits, which seems to be linked with three important factors of the AD-systemic inflammation, oxidative stress, and blood cell damage-and may be a promising adjuvant therapy against the AD progression.

Silymarin protects against radiocontrast-induced nephropathy in mice.

Silymarin, an extract from Silybum marianum (milk thistle) containing a standardized mixture of flavonolignans that ameliorates some types of liver disease and, more recently, kidney damage, could be used for the ROS-scavenging effect of these antioxidants. Furthermore, contrast-induced nephropathy (CIN) is an iatrogenic impairment of renal function in patients subjected to angiographic procedures for which there is not yet a successful preventative treatment. Recent evidence has shown that this event is related to tubular/vascular injury activated mainly by oxidative stress. However, whether this bioavailable and pharmacologically safe extract protects against CIN is not clear. We proposed to evaluate the possible protective role of the antioxidant silymarin in an experimental model of CIN. Adult male Swiss mice were separated into 6 groups and pretreated orally with silymarin (50, 200 and 300 mg/kg), N-acetylcysteine (200 mg/kg) or vehicle for 5 days before the CIN and control groups. Renal function was analyzed by plasma creatinine, urea and cystatin C levels. Additionally, blood reactive oxygen species (ROS) were evaluated using ROS bioavailability, protein oxidation and DNA damage. Renal oxidative damage was evaluated using apoptosis/cell viability assays and histological analysis. We showed that silymarin preserved renal function and decreased systemic and renal oxidative damage (antigenotoxic and antiapoptotic properties, respectively) in a dose-dependent manner and was superior to conventional treatment with N-acetylcysteine. Histologically, silymarin treatment also had beneficial effects on renal glomerular and tubular injuries. Therefore, silymarin prophylaxis may be an interesting strategy for the prevention of CIN.

Worsening of Oxidative Stress, DNA Damage, and Atherosclerotic Lesions in Aged LDLr-/- Mice after Consumption of Guarana Soft Drinks.

BACKGROUND: Excessive consumption of soft drinks (SD) has become a health problem worldwide due to its association with related cardiovascular diseases. We investigated the possible impacts associated with the consumption of Brazilian guarana (normal and zero) SD in dyslipidemic mice, thus mitigating potential clinical confounders such as poor-quality diet, lifestyle, body composition, and/or comorbidities. METHODS: Sixteen-month-old LDLr-/- mice were divided into the following groups: (1) control; (2) GSD: normal guarana SD; and (3) Z-GSD: zero guarana SD. All were fed ad libitum, and blood pressure was measured noninvasively. After 8 weeks, aorta, blood, liver, and stomach samples were collected for histological and biochemical analyses. RESULTS: Guarana soft drinks increased atherosclerosis (~60%) and were associated with hypercholesterolemia, hypertension, oxidative stress, DNA fragmentation, and apoptosis (~2-fold) of blood cells, besides presenting an increase in liver and gastric damage even in normoglycemia. Interestingly, Z-GSD did not cause the aforementioned changes, except in hemodynamic and renal parameters. CONCLUSIONS: Chronic administration of GSD is prooxidative, compromising the cardiovascular, gastric, and hepatic systems; the effects are due at least in part to free sugar consumption but not to guarana extract per se.

Avocado seeds (Persea americana Mill.) prevents indomethacin-induced gastric ulcer in mice.

The long-term use of anti-inflammatory drugs is the most common cause of gastric ulcer disease, one of the major gastrointestinal disorders affecting people worldwide. Persea americana Mill. (avocado) seed is a by-product generally discarded as waste, but can be used to treat gastric disorder due to its anti-inflammatory, antioxidant and antimicrobial activities. The aim of the present study was to evaluate the potential protective effects of the ethyl acetate fraction of avocado seeds (SEAP) extracts against indomethacin-induced gastric ulcer in mice. It was found that SEAP were effective in mitigating oxidative stress through a decrease on the oxidized products levels (reduction of 90% in lipid peroxidation in plasma) and increasing superoxide dismutase enzyme (SOD) activity (4.25-fold increase compared to the indomethacin group), also preventing the rise in ulcer and lesions areas (92% of protection) and histological changes induced by indomethacin. Chemical analysis using mass spectrometry by (-)-ESI-FT-ICR MS revealed the presence of (-)-epicatechin and (+)-catechin, confirmed by HPLC-DAD, and other important phenolic compounds in avocado seeds, such as caffeoylquinic acid, flavonoids, phenylpropanoids and tannins, substances that promote inhibition of pathways involved in gastric ulcer formation. Thus, avocado seeds extract may be a suitable natural source for the prevention and treatment of gastric ulcer.

Gastroprotective effect of oral kefir on indomethacin-induced acute gastric lesions in mice: Impact on oxidative stress.

AIMS: This study investigated the gastroprotective effects and the systemic oxidative status of oral kefir pretreatment in albino mice submitted to acute gastric ulcer induced by indomethacin. MAIN METHODS: Male Swiss mice were divided into three groups (n = 7): Vehicle (0.3 mL of whole milk/100 g body weight, pH adjusted to 5.0), Kefir (0.3 mL of kefir/100 g body weight) and Proton Pump Inhibitor (PPI, 30 mg/kg of lansoprazole), via gavage for 14 days. Animals were fasted for 16 h and treated orally with indomethacin (40 mg/kg). After 6 h the animals were euthanized, the blood samples were obtained and used for the determination of ROS production, oxidation of macromolecules and apoptosis. The stomachs were removed, opened by the greater curvature, and a macroscopic analysis of the gastric lesions was performed. KEY FINDINGS: Our findings demonstrated that the symbiotic kefir significantly alleviated blood oxidative stress by reducing superoxide anion, hydrogen peroxide and hydroxyl/peroxynitrite radicals, thereby leading to reduced oxidative damage to macromolecules due to a decreased oxidative stress status in induced gastric lesions. These anti-oxidative properties might contribute favorably to the ulcer attenuation in the kefir group. SIGNIFICANCE: Taken together, these findings support a significant role played by the antioxidant actions of kefir in counteracting the gastric damage induced by this cyclooxygenase inhibitor. It is also worthy to mention that, kefir also exerted the gastroprotective property partly by inhibiting oxidative systemic damage. Based on these considerations, it was implied that kefir might be a contributor for the ROS-scavenging effect.

Sildenafil prevents renal dysfunction in contrast media-induced nephropathy in Wistar rats.

Contrast-induced nephropathy (CIN) is an iatrogenic medical event in stable cardiology patients that may lead to acute renal failure. There is no current successful therapy to manage CIN. Increasing evidence in experimental models and humans has suggested that this disease is associated with renal tubular and vascular injury triggered by oxidative stress. Considering the importance of reactive oxygen species (ROS) generation in the pathogenesis of CIN, the goal of the present study was to evaluate the effects of sildenafil on CIN development. Male Wistar rats were divided into control, CIN, and CIN pretreated with sildenafil (50 mg/kg/day). CIN was induced by water deprivation, NG-nitro-L-arginine methyl ester + indomethacin injections (10 mg/kg, intraperitoneally) and intravenous iohexol administration (3 g/kg). Renal function was evaluated through glomerular filtration rate (GFR), renal blood flow (RBF), plasma creatinine, uremia, and proteinuria. Oxidative stress was assessed by flow cytometry for intracellular ROS. Treatment with sildenafil attenuated the marked reduction of GFR and RBF in the CIN group. Moreover, sildenafil treatment in CIN rats reduced plasma creatinine, uremia, and proteinuria. Flow cytometry demonstrated that sildenafil attenuated the ROS production in the CIN group. These data suggest that sildenafil may be a new therapeutic agent to prevent CIN through its ability to preserve renal function and attenuate oxidative stress.

Resin from Virola oleifera Protects Against Radiocontrast-Induced Nephropathy in Mice.

Contrast-induced nephropathy (CIN) is an iatrogenic medical event for which there is not yet a successful therapy. Increasing evidence in rodents has suggested that this disease is associated with renal tubular and vascular injury that is triggered directly by oxidative stress. In the present study, we evaluated whether the antioxidant resin from Virola oleifera (RV) could attenuate renal damage in an experimental mouse model of CIN. Adult male Swiss mice were divided into six groups and pre-treated orally with RV (10, 100 and 300 mg/kg), N-acetylcysteine (200 mg/kg) or vehicle for 5 days before the induction of CIN and Control group. Renal function was assessed by measuring plasma creatinine and urea levels. Additionally, renal oxidative stress and apoptosis/cell viability were determined with flow cytometry. Finally, kidney tissues were sectioned for histopathological examination. In this CIN model, pre-treatment with RV improved renal function, lowered the mortality rate, and reduced oxidative stress and apoptosis in both the medulla and cortex renal cells in a dose-dependent manner. Moreover, the RV treatment had beneficial effects on kidney histopathology that were superior to the standard treatment with N-acetylcysteine. These data suggest that because of its antioxidative and antiapoptotic effects and its ability to preserve renal function, resin from Virola oleifera may have potential as a new therapeutic approach for preventing CIN.