Cannabidiol protects C2C12 myotubes against cisplatin-induced atrophy by regulating oxidative stress.

Cancer and chemotherapy induce a severe loss of muscle mass (known as cachexia), which negatively impact cancer treatment and patient survival. The aim of the present study was to investigate whether cannabidiol (CBD) administration may potentially antagonize the effects of cisplatin in inducing muscle atrophy, using a model of myotubes in culture. Cisplatin treatment resulted in a reduction of myotube diameter (15.7 ± 0.3 vs. 22.2 ± 0.5 µm, P < 0.01) that was restored to control level with 5 µM CBD (20.1 ± 0.4 µM, P < 0.01). Protein homeostasis was severely altered with a ≈70% reduction in protein synthesis (P < 0.01) and a twofold increase in proteolysis (P < 0.05) in response to cisplatin. Both parameters were dose dependently restored by CBD cotreatment. Cisplatin treatment was associated with increased thiobarbituric acid reactive substances (TBARS) content (0.21 ± 0.03 to 0.48 ± 0.03 nmol/mg prot, P < 0.05), catalase activity (0.24 ± 0.01 vs. 0.13 ± 0.02 nmol/min/µg prot, P < 0.01), whereas CBD cotreatment normalized TBARS content to control values (0.22 ± 0.01 nmol/mg prot, P < 0.01) and reduced catalase activity (0.17 ± 0.01 nmol/min/µg prot, P < 0.05). These changes were associated with increased mRNA expression of GPX1, SOD1, SOD2, and CAT mRNA expression in response to cisplatin (P < 0.01), which was corrected by CBD cotreatment (P < 0.05). Finally, cisplatin treatment increased the mitochondrial protein content of NDUFB8, UQCRC2, COX4, and VDAC1 (involved in mitochondrial respiration and apoptosis), and CBD cotreatment restored their expression to control values. Altogether, our results demonstrated that CBD antagonize the cisplatin-induced C2C12 myotube atrophy and could be used as an adjuvant in the treatment of cancer cachexia to help maintain muscle mass and improve patient quality of life.NEW & NOTEWORTHY In an in vitro model, cisplatin treatment led to myotube atrophy associated with dysregulation of protein homeostasis and increased oxidative stress, resulting in increased apoptosis. Cotreatment with cannabidiol was able to prevent this phenotype by promoting protein homeostasis and reducing oxidative stress.

Effects of fullerene C60 on liver tissue in liver ischemia reperfusion injury in rats undergoing sevoflurane anesthesia.

This study aimed to investigate the effects of fullerene C60 on rat liver tissue in a liver ischemia reperfusion injury (IRI) model under sevoflurane anesthesia to evaluate the ability of nanoparticles to prevent hepatic complications. A total of 36 adult female Wistar Albino rats were divided into six groups, each containing six groups as follows: sham group (Group S), fullerene C60 group (Group FC60), ischemia-reperfusion group (Group IR), ischemia-reperfusion-sevoflurane group (Group IR-Sevo), ischemia-reperfusion-fullerene C60 group (Group IR-FC60), and ischemia-reperfusion-fullerene C60-sevoflurane group (Group IR-FC60-Sevo). Fullerene C60 100 mg/kg was administered to IR-FC60 and IR-FC60-Sevo groups. In the IR group, 2 h of ischemia and 2 h of reperfusion were performed. At the end of reperfusion, liver tissues were removed for biochemical assays and histopathological examinations. Hepatocyte degeneration, sinusoidal dilatation, prenecrotic cells, and mononuclear cell infiltration in the parenchyma were significantly higher in Group IR than in all other groups. Thiobarbituric acid reactive substances levels were significantly higher in Group IR than in the other groups, and the lowest thiobarbituric acid reactive substances level was in Group IR-FC60 than in the other groups, except for Groups S and FC60. Catalase and Glutathione-S-transferase activities were reduced in the IR group compared to all other groups. Fullerene C60 had protective effects against liver IR injury in rats under sevoflurane anesthesia. The use of fullerene C60 could reduce the adverse effects of IRI and the associated costs of liver transplantation surgery.

Ginsenoside Rh4 inhibits the malignant progression of multiple myeloma and induces ferroptosis by regulating SIRT2.

Multiple myeloma (MM) has a high mortality rate, and the exploration of therapeutic drugs for MM with low side effects is a hot topic at the moment. Ginsenoside Rh4 has been shown to inhibit tumour growth in many cancers. However, the role of ginsenoside Rh4 in MM and its reaction mechanism have not been reported so far. After the treatment with different concentrations of ginsenoside Rh4, the proliferation of NCI-H929 cells was detected by Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine staining. The cell apoptosis and cycle arrest were detected by flow cytometry and western blot. The thiobarbituric acid-reactive substances (TBARS) production was assessed with TBARS assay, whereas Fe2+ fluorescence assay was used for the measurement of Fe2+ level. The production of reactive oxygen species was evaluated with dichloro-dihydro-fluorescein diacetate staining, and western blot was applied for the estimation of ferroptosis-related proteins. The potential targets of ginsenoside Rh4 were predicted by molecular docking technology and verified by western blot. The transfection efficacy of overexpression-SIRT2 was examined with quantitative reverse transcription polymerase chain reaction and western blot. To figure out the detailed reaction mechanism between ginsenoside Rh4 and SIRT2 in MM, rescue experiments were conducted. We found that ginsenoside Rh4 inhibited cell proliferation, induced cell apoptosis, promoted cycle arrest and facilitated ferroptosis in MM. Moreover, ginsenoside Rh4 inhibited SIRT2 expression in MM cells. The overexpression of SIRT2 reversed the effects of ginsenoside Rh4 on cell proliferation, cell apoptosis, cycle arrest and ferroptosis in MM. Overall, ginsenoside Rh4 inhibited the malignant progression of MM and induced ferroptosis by regulating SIRT2.

Sub­chronic administration of lead alters markers of oxidative stress, acetylcholinesterase and Na+K+­ATPase activities in rat brain.

This study investigated the effects of sub­chronic administration of lead (Pb) acetate on thiobarbituric acid reactive substances (TBA­RS), total sulfhydryl content, protein carbonyl content, antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GSH­Px]), acetylcholinesterase (AChE), and Na+K+­ATPase in the cerebral structures of rats. Male Wistar rats aged 60 days were treated with saline (control group) or Pb (treatment group), at various doses, by gavage, once a day for 35 days. The animals were sacrificed twelve hours after the last administration, and the cerebellum, hippocampus and cerebral cortex were removed. The results showed that Pb did not alter the evaluated oxidative stress parameters. Furthermore, Pb (64 and/or 128 mg/kg) altered SOD in the cerebellum, cerebral cortex and hippocampus. Pb (128 mg/kg) altered CAT in the cerebellum and cerebral cortex and GSH­Px in the cerebral cortex. Also, Pb (64 mg/kg and 128 mg/kg) altered GSH­Px in the cerebellum. Moreover, Pb (128 mg/kg) increased AChE in the hippocampus and decreased Na+K+­ATPase in the cerebellum and hippocampus. In conclusion, sub­chronic exposure to Pb (occupational and environmental intoxication) altered antioxidant enzymes, AChE, and Na+K+­ATPase, contributing to cerebral dysfunction.

Antioxidant and Anti-inflammatory Effects of α-Lipoic Acid on Lipopolysaccharide-induced Oxidative Stress in Rat Kidney.

α-Lipoic acid (α-LA) is a naturally occurring organosulfur component. Oxidative stress plays an essential role in the pathogenesis of various diseases, such as kidney and cardiovascular diseases, diabetes, neurodegenerative disorders, cancer and aging. Kidneys are especially vulnerable to oxidative stress and damage. The aim of the study was to evaluate the effect of α-LA on lipopolysaccharide (LPS)-induced oxidative stress parameters in rat kidneys. The experimental rats were divided into four groups: I-control (0.9% NaCl i.v.); II-α-LA (60 mg/kg b.w. i.v.); III-LPS (30 mg/kg b.w. i.v.); and IV-LPS + LA (30 mg/kg b.w. i.v. and 60 mg/kg b.w. i.v., respectively). In kidney homogenates the concentration of thiobarbituric acid reactive substances (TBARS), hydrogen peroxide (H2O2), sulfhydryl groups (-SH), total protein, superoxide dismutase (SOD), total glutathione (tGSH), reduced glutathione (GSH), glutathione disulphide (GSSG) and the GSH/GSSG ratio were determined. In addition, the levels of tumour necrosis factor (TNF)-α, and interleukin (IL)-6 were measured to assess inflammation and was estimated kidney oedema. Studies have shown that α-LA administered after LPS administration attenuated kidney oedema and significantly decreased TBARS, H2O2, TNF-α, and IL-6 levels in rat kidneys. α-LA also resulted in increase -SH group, total protein, and SOD levels and ameliorated the GSH redox status when compared to the LPS group. The results suggest that α-LA plays an important role against LPS-induced oxidative stress in kidney tissue as well as downregulating the expression of pro-inflammatory cytokines.

Evidences of metabolic alterations and cellular damage in different tissues of scallops Aequipecten tehuelchus exposed to cadmium.

Scallops Aequipecten tehuelchus (Patagonia, Argentina) were exposed to 0, 2, 5 and 12 µg Cd/L for 7 and 14 days, causing in digestive gland a significant production of reactive oxygen and nitrogen species (RONS), induction of catalase (CAT) and glutathione S-transferase (GST) activities and metallothioneins (MT) synthesis. In gills, there was inhibition of GST and induction of CAT, MT and α-tocopherol (α-Toc). In muscle, a significant increment of MT was also registered and inhibition of CAT. Lipid peroxidation, measured as TBARS, was not promoted in any tissue. More significant effects were observed in digestive gland than in gills and muscle, evidencing the critical role of digestive gland in Cd accumulation and metabolisation. This research would evidence dose-dependent effects of Cd on MT, GST, CAT and α-Toc in the three organs assayed, as well as a time-dependent effect of Cd on the response of CAT, GST and TBARS in digestive gland.

Effects of Iron on Efficacy of Photodynamic Therapy Using Photolon in a Mouse Model of CT26 Colon Cancer.

BACKGROUND: Photodynamic therapy (PDT) -a minimally invasive anti-cancer therapy-is undergoing experimental studies to increase its anti-cancer effects. This study investigated the influence of iron on the anti-cancer effects of PDT. METHODS: PDT was performed in a cancer-bearing mouse model, which was created by using a murine colon carcinoma (CT26) cell line after administration of Photolon and iron. Tumor volume and the results of TdT-mediated dUTP-biotin nick end labeling (TUNEL), 8-OHdG, and TBARS assays were used to measure anti-cancer effect. RESULTS: On day 14, tumor volume had increased by 49% in the PDT group and decreased by 72% in the iron+PDT group. The percentage of TUNEL-positive cells in tumor tissues was 45% in the PDT group and 69% in the iron+PDT group, suggesting that the proportion of TUNEL-positive cells had increased in the iron+PDT group. The 8-OHdG content in tumor tissues was 33% higher in the iron+PDT group than in the PDT group. The TBARS content in tumor tissues was 46% higher in the iron+PDT group than in the PDT group. CONCLUSIONS: Iron enhances the anti-cancer effect of PDT using Photolon, most likely by increasing oxidative damage.

Melatonin decreases plasma TNF-α and improves nonenzymatic antioxidant defence and insulin sensitivity in rats with apical periodontitis fed a high-fat diet.

AIM: To analyse the effects of melatonin (ME) treatment on oxidative stress and insulin resistance (IR) in rats with apical periodontitis (AP) fed a high-fat diet (HFD). METHODOLOGY: Eighty 60-day-old rats were divided into eight groups: control (CN), AP, HFD with AP (HFDAP), control with ME (CNME), AP with ME (APME), HFD with ME (HFDME) and HFD with AP+ME (HFDAPME). The animals from the HFD groups were fed a HFD throughout the experimental period. On day 7, the animals from the AP groups were subjected to experimental AP, and after 70 days, the ME groups were treated for 30 days. Glycaemia, insulinaemia, homeostatic model assessment for IR index, tumour necrosis factor-α (TNF-α), and interleukin-6 were analysed in plasma using biochemical tests and enzyme-linked immunosorbent assay. Thiobarbituric acid-reactive substances (TBARS), carbonyl protein (CP), superoxide dismutase (SOD), catalase, glutathione peroxidase, glutathione (GSH) and total antioxidant capacity (ferric reducing antioxidant power [FRAP]) were analysed in the gastrocnemius muscle. RESULTS: (1) Association of AP and HDF exacerbated IR, and ME treatment improved this alteration; (2) AP and HFD and their association showed increased TNF-α, and ME reversed it; (3) TBARS increased in the AP and HFDAP groups, and ME reversed only in the group with the association of disease and diet; (4) CP increased in all HFD groups and improved in the ME groups; (5) GSH activity decreased in all experimental groups, and ME increased this parameter only in the CN and AP groups; (6) FRAP did not change between the groups, but ME treatment increased its activity in the AP and HFD groups; (7) ME increased SOD in the CN and AP groups. CONCLUSION: Apical periodontitis and HFD promoted IR, and the association of AP with diet promoted IR exacerbation; this resistance might have been caused by an increase in TNF-α. AP promoted more intense changes in lipid oxidative damage than in protein oxidative damage. In non-enzymatic antioxidant defence, it was observed that both AP and HFD and their association promoted a decrease in GSH levels. Overall, ME treatment reversed changes such as oxidative stress and IR.

Protective Effects of Kefir Against Unpredictable Chronic Stress Alterations in Mice Central Nervous System, Heart, and Kidney.

Kefir is a probiotic mixture with anxiolytic and antioxidant properties. Chronic stress can lead to anxiety disorders and increase oxidative damage in organs such as the heart and kidney. In this study, we examined whether kefir ameliorates the anxiety-like behavior of mice submitted to chronic unpredictable stress (CUS) by modulating brain-derived neurotrophic factor (BDNF) and corticosterone levels and whether kefir modifies the oxidative parameters in the heart and kidney of mice. Male Swiss mice received kefir (0.3 mL/100 g/day) or milk for 30 days (gavage). On the 10th day, the mice were submitted to CUS. Behavioral analysis was performed using the elevated plus maze and forced swimming tests. BDNF levels were analyzed in brain tissues. Heart and kidney superoxide dismutase (SOD), catalase, glutathione (GSH), thiobarbituric acid reactive substances (TBARS), 3-nitrotyrosine, metalloproteinase-2 (MMP-2), and plasma corticosterone were evaluated. Kefir reverted the CUS-induced decrease in the time spent in the open arms, the increase in grooming frequency, and decrease in the head dipping frequency, but not the reduced immobility time. CUS decreased the cerebellum BDNF levels and increased corticosterone levels, which were restored by Kefir. Neither catalase and SOD activities nor GSH, TBARS, 3-nitrotyrosine, and MMP-2 were modified by CUS in the heart. In the kidney, CUS increased 3-nitrotyrosine and MMP-2. Kefir increased the antioxidant defense in the heart and kidney of control and CUS mice. These results suggest that kefir ameliorated CUS-induced anxiety-like behavior by modulating brain BDNF and corticosterone levels. Kefir also increased the antioxidant defense of mice heart and kidney.

Investigation into the protective effects of Naringenin in phthalates-induced reproductive damage.

OBJECTIVE: Di-n-butyl phthalate (DBP) is a ubiquitous environmental pollutant, extensively used as a plasticizer in many products, including plastics, cosmetics, and medical devices. Naringenin (NAR) is a flavonoid belonging to the flavanones subclass. It is widely distributed in several citrus fruits, bergamot, tomatoes, and other fruits. It is also found in its glycoside form (mainly naringin). Several biological activities have been ascribed to this phytochemical: antioxidant, antitumor, antiviral, antibacterial, anti-inflammatory, antiadipogenic, and cardioprotective effects. This study hypothesized that phthalates' possible reproductive damage mechanism is oxidative attack, and naringenin could have a protective effect against radical forms in the body through its antioxidant properties. MATERIALS AND METHODS: Thirty-two male rats were used in our study (n=8 each). Rats were randomly divided into four groups: Control, DBP, DBP +NAR and NAR. Phthalate (DBP) and NAR were administered through gastric oral gavage (phthalate group 500 mg/kg/day DBP; NAR group 50 mg/kg/day NAR). At the end of four weeks, testis tissue samples were taken under anesthesia. Testis tissue and blood samples were collected from the four groups in this study. Histological, biochemical and spermatological analyses were conducted. RESULTS: Tissue samples from the control and NAR groups showed normal histological appearance on light microscopy. The DBP group exhibited deterioration in seminiferous tubules, vascular congestion in capsule, vascular congestion between the seminiferous tubules, edema in the intestinal area and vacuolization, arrested spermatocytes in different stages of division; sloughing of cells into the seminiferous tubular lumen was observed. It was also observed that NAR treatment significantly inhibited and prevented the histopathological damage caused by DBP. Tissue TBARS, antioxidant parameters, sperm motility, sperm density and abnormal spermatozoon ratios were determined. As a result, it was shown that DBP caused oxidative damage by increasing TBARS levels and decreasing antioxidant parameters, increased abnormal sperm rate and decreased sperm motility, and concentration and histopathological damage, so the antioxidant activity of naringenin inhibited this damage. CONCLUSIONS: DBP had toxic effects in rat testis tissue; NAR treatment ameliorated these effects. Further studies are warranted to confirm our findings.

Assessment of redox state and biochemical parameters of salivary glands in rats treated with anti-obesity drug sibutramine hydrochloride.

OBJECTIVES: To investigate the effects of anti-obesity drug sibutramine hydrochloride (SB) on redox state and biochemical parameters in the salivary glands. MATERIALS AND METHODS: Adult male Wistar rats were randomly divided into the following groups (n = 8 per group): control rats treated with vehicle (C) and rats treated with SB (10 mg/kg/day) by intragastric gavage for 28 days. The parotid (PG) and submandibular (SMG) glands were processed using histomorphometric analysis, and total protein, amylase, mucin, and oxidative damage to lipids were determined by measuring the formation of thiobarbituric acid reactive substances (TBARS), total antioxidant capacity (TAC), uric acid (UA), total glutathione (tGSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), and AKT phosphorylation. RESULTS: SB decreased the acinar area, and increased the stromal area in PG, while no effect on the morphometric parameters was observed in SMG. SB also increased oxidative damage to lipids (TBARs). The SB group showed lower total protein, amylase, TAC, UA, tGSH, SOD, CAT, and GPx than the C group in PG, while in SMG, SB decreased total protein, mucin, tGSH, SOD, CAT, and GPx. However, increased AKT phosphorylation observed in both salivary glands suggests that SB exerts low-intensity oxidative stress. CONCLUSIONS: SB impaired enzymatic and non-enzymatic antioxidant defenses in the salivary glands of rats. CLINICAL RELEVANCE: Chronic treatment with SB could mitigate salivary gland dysfunction due to disturbance of redox state.

Amelioration of oxidative stress utilizing nanoemulsion loaded with bromocriptine and glutathione for the management of Parkinson's disease.

Parkinson's disease (PD) is triggered by the formation of free radicals in dopaminergic neurons, which results in oxidative stress-induced neurodegeneration. The objective of the work was to relieve oxidative stress by employing intranasal delivery of Bromocriptine Mesylate (BRM) and Glutathione (GSH) loaded nanoemulsion for the better management of PD. The depth of permeation of the nanoemulsion was assessed through confocal laser scanning microscopy (CLSM) which revealed higher nanoemulsion permeation in contrast to suspension. Biocompatibility of nanoemulsion was confirmed by nasal cilio toxicity study. The DPPH study showed that the nanoemulsion had significant antioxidant activity. Biochemical estimation studies in Wistar rats were carried out in order to determine the effect of nanoemulsion on oxidative stress. The levels of GSH, superoxide dismutase (SOD), and catalase (CAT) were significantly enhanced; and the level of thiobarbituric acid reactive substances (TBARS) was significantly reduced after the intranasal administration of nanoemulsion in the haloperidol-induced model of PD. Furthermore, the levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were also determined which reduced significantly after the administration of nanoemulsion. The oxidative stress levels were lowered with nanoemulsion, showing the combined antioxidant capability of BRM and GSH. The neuroprotective effect of the prepared nanoemulsion was confirmed by histopathological studies. Pharmacokinetic study revealed a higher concentration of BRM and GSH in the brain of Wistar rats after intranasal administration of nanoemulsion with a higher Brain/Plasma ratio. A higher value of AUC(0-8) of nanoemulsion in the brain after intranasal administration revealed that BRM and GSH remained in the brain for a longer period due to sustained release from nanoemulsion. According to the findings, BRM and GSH loaded nanoemulsion has the potential to provide a combined and synergistic anti-oxidant effect for efficient management of PD.

Antilipoperoxidative and anti-inflammatory efficacy of multifunctional sunscreens containing ferulic acid

Unprotected chronic exposure to ultraviolet radiation generates many harmful effects to human skin and UV filters are essential to health, however, traditional sunscreens do not provide enough protection against cutaneous oxidative stress, a process amplified by UV radiation. Therefore, is been proposed the development of multifunctional photoprotective formulations, acting in the absorption/reflection of UV radiation and assisting in cutaneous homeostasis. In the present study, ferulic acid is used in conjunction with two sunscreens, bemotrizinol and ethylhexyl triazone, for the determination of biosafety and efficacy methods, using techniques that better elucidate the effects of ferulic acid. Skin permeation assays were performed by applying a formulation containing the three substances in the stratum corneum of volunteers, which were removed by the tape stripping method (ex vivo) with follow quantification by high performance liquid chromatography (HPLC). The test was able to evaluate the penetration depth of the substances, characterizing them. In addition, the simultaneous quantification of the three substances was performed by a single and fast method, facilitating their analysis and improving the technique. Also, TBARS (thiobarbituric acid reactive substances) assays were performed in stratum corneum removed by tape stripping (ex vivo), evaluating the potential of cutaneous lipid peroxidation, with or without ferulic acid. To date, it is the first time that TBARS method is used to characterize the stratum corneum (ex vivo) and quantified by HPLC. The protocol developed may aid in the efficacy of antioxidant agents in studies aimed at elucidating the level of lipid peroxidation caused by drugs and cosmetics, and even in carrying out baseline studies characterizing different ethnicities and genders. As last, an anti-inflammatory in vivo assay with Laser Doppler flowmetry equipment was used to compare the sunscreen formulation with or without ferulic acid. Data indicated that the antioxidant reduced the angular coefficient of the perfusion units, mitigating the inflammatory effects. Furthermore, a significant difference was found between the genders, suggesting a more pronounced inflammatory reaction in women. Ferulic acid proved to be a valuable resource, besides being safe and raise the SPF of sunscreens, it also mitigates the effects of inflammation

A exposição crônica desprotegida à radiação ultravioleta (UV) contribui para o desenvolvimento de câncer de pele e os filtros solares são relevantes para evitar tais efeitos prejudiciais, porém, os protetores solares tradicionais não geram proteção suficiente contra o estresse oxidativo cutâneo. Logo, espera-se o desenvolvimento de formulações fotoprotetoras multifuncionais, atuando não somente na absorção e/ou reflexão da radiação UV, mas, também, auxiliando na homeostase cutânea, com presença de agentes antioxidantes. No presente estudo foi utilizado o ácido ferúlico conjuntamente com dois filtros solares, o bemotrizinol e a triazona de octila, para determinação de métodos de segurança e eficácia, utilizando técnicas que melhor elucidem e comprovem os efeitos do ácido ferúlico. Foram realizados ensaios de permeação cutânea pela aplicação tópica de formulação contendo as três substâncias em voluntários, sendo o estrato córneo retirado pelo método de tape stripping (ex vivo) com subsequente quantificação por cromatografia líquida de alta eficiência (CLAE). O ensaio pôde avaliar a profundidade de penetração das substâncias, caracterizando-as. Ademais, a quantificação simultânea das três substâncias foi efetuada por método único e rápido, facilitando análise com aprimoramento da técnica. Em adição, foi realizado ensaios de TBARS (substâncias reativas ao ácido tiobarbitúrico) em estrato córneo removido por tape stripping (ex vivo), para avaliar o potencial de peroxidação lipídica cutânea, contendo ou não o ácido ferúlico. Até o presente momento, é a primeira vez que o método TBARS é utilizado para caracterização do estrato córneo (ex vivo) e quantificada por CLAE. O protocolo desenvolvido pode auxiliar na eficácia de agentes antioxidantes, em estudos que visam elucidar o nível de peroxidação lipídica causada por medicamentos e cosméticos e, até mesmo, na realização de estudos de base, caracterizando etnias e gêneros. Ademais, um ensaio anti-inflamatório in vivo com equipamento de fluxometria Laser Doppler foi utilizado para comparar a formulação fotoprotetora com ou sem ácido ferúlico. Os dados indicaram que o antioxidante reduziu o coeficiente angular das unidades de perfusão, mitigando os efeitos inflamatórios. Ainda, foi identificada diferença entre os gêneros, sugerindo reação inflamatória mais pronunciada em mulheres. O ácido ferúlico provou ser um recurso valioso, além de ser seguro e elevar o FPS dos fotoprotetores, também atenuando os efeitos da inflamação

Therapeutic effect of rocket seeds (Eruca sativa L.) against hydroxyapatite nanoparticles injection induced cardiac toxicity in rats.

Hydroxyapatite is bio-ceramic materials with a calcium to phosphorus proportion like to that of normal bone and teeth. The current study meant to examine the cardiac toxicity by hydroxyapatite nanoparticles (HAP NPs) and the protective effect of the rocket seeds in treatments. An aggregate of 40 male Wistar rodents were partitioned into 4 equal groups [Gp1, control; Gp2, rocket seeds extract (RS); Gp3, HAP NPs; Gp4, HAP NPs+RS]. Current results exhibit that; HAP NPs induce a significant increase in myoglobin, LDH (lactate dehydrogenase), CK-MB (creatinine kinase) and CK (creatinine kinase) levels, cardiac thiobarbituric acid-reactive substances (TBARS), injury and P53 expressions. In contrast; a significant reduction in cardiac catalase, reduced glutathione (GSH) and superoxide dismutase (SOD) as compared to control group. Post treatment of rat with HAP NPs and rocket seeds extract (HAP NPs+RS) improved the cardiac functions and structure. Rocket seeds extract may offer advantages against the harmful effects of hydroxyapatite nanoparticles.

Change in soluble epoxide hydrolase (sEH) during cisplatin-induced acute renal failure in mice.

Cisplatin is one of the most effective chemotherapeutic agents against various types of cancers; however, it is also associated with nephrotoxicity. Recently, it was reported that inflammatory mechanisms play a key role in the development of nephrotoxicity. Epoxyeicosatrienoic acids (EETs) have an anti-inflammatory effect and are metabolized by soluble epoxide hydrolase (sEH: encoded by EPHX2 gene). Here, we determined the change in sEH activity and EPHX2 expression in renal tissue associated with the development of cisplatin-induced nephrotoxicity. Cisplatin administration decreased hydrolase activity accompanied by down-regulation of sEH and EPHX2 expression. The down-regulation occurred prior to the elevation of blood urea nitrogen (BUN) and tumor necrosis factor-α (TNF-α) gene expression or at treatment with low dose cisplatin. In addition, a negative correlation was found between EPHX2 expression and renal thiobarbituric acid reactive substance (TBARS), and edaravone, a radical scavenger, administration did not down-regulate expression of this gene. The results of this study suggest that cisplatin decreased sEH activity through the down-regulation of sEH and EPHX2 expression, and this down-regulation was involved in a negative feedback loop to protect renal tissue from further damage. Thus, sEH is a potential therapeutic target of cisplatin-induced nephrotoxicity.

Experimental Lung Injury Promotes Changes in Oxidative/Nitrative Status and Inflammatory Markers in Cerebral Cortex of Rats.

In the present study, we investigate the effect of lung injury on parameters of oxidative/nitrative stress [reactive oxygen species production, nitrite levels, thiobarbituric acid-reactive substances (TBARS), carbonyl content, sulfhydryl content, activities of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase), total radical-trapping antioxidant potential, glutathione content, and glucose-6-phosphate dehydrogenase], as well as on inflammation mediators [immunocontent of nuclear factor-kappaB (NF-κB) total (p65), NF-κB phosphorylated (pp65) subunit (cytosolic and nuclear), TNF-α, IL-1ß, IL-6, and IL-10] in the cerebral cortex. Cytokine levels in serum were also evaluated. Adult Wistar rats were submitted to lung injury induced by intratracheal instillation of lipopolysaccharide in a dose of 100 µg/100 g body weight. Sham group (control) received isotonic saline instillation. Twelve hours after the injury, rats were decapitated and blood samples were collected and the cerebral cortex dissected out. Results showed an increase in reactive oxygen species production, TBARS, and nitrite and carbonyl levels in the cerebral cortex of rats submitted to lung injury. Antioxidant enzymatic defenses were altered, superoxide dismutase and glutathione peroxidase activities decreased, and catalase activity increased. Non-enzymatic antioxidant capacity, glutathione content, and glucose-6-phosphate dehydrogenase were decreased. Inflammatory parameters were also altered in the cerebral cortex of rats subjected to lung injury; it was observed an increase in the immunocontent of NF-κB/p65 (nuclear fraction) and NF-κB/pp65 (cytosolic and nuclear faction), as well as an increase in TNF-α, IL-1ß, IL-6, and IL-10 levels. The levels of IL-10 also increased in the serum. Our findings show that the lung injury alters oxidative/nitrative status and induces inflammation in the cerebral cortex of rats, which might be associated with cognitive impairments present in patients with lung injury.

In vitro evaluation of free radical scavenging activity of Codariocalyx motorius root extract.

OBJECTIVE: To determine the phenolic content in Codariocalyx motorius root extract and to evaluate its antioxidant properties using various in vitro assay systems. METHODS: The antioxidant activity was evaluated based on scavenging of 1,1-diphenyl-2-picrylhydrazyl, hydroxyl radicals, superoxide anions, nitric oxide, hydrogen peroxide, peroxynitrite, reducing power and by inhibition of lipid peroxidation which was estimated in terms of thiobarbituric acid reactive substances. RESULTS: The root extract of the Codariocalyx motorius (C. motorius) exhibited potent total antioxidant activity that increased with increasing amount of extract concentration, which was compared with standard drug such as quercetin, butylated hydroxytoluene, tocopherol at different concentrations. The different concentrations of the extracts showed inhibition on lipid peroxidation. In addition, the extracts had effective reducing power, free radical scavenging, super oxide anion scavenging, nitric oxide scavenging, lipid peroxidation, and total phenolic content depending on concentration. High correlation between total phenolic contents and scavenging potential of different reactive oxygen species (r(2)=0.831-0.978) indicated the polyphenols as the main antioxidants. CONCLUSIONS: Codariocalyx motorius (C. motorius) root possess the highly active antioxidant substance which can be used for the treatment of oxidative stress-related diseases.

Attenuation of insulin resistance, metabolic syndrome and hepatic oxidative stress by resveratrol in fructose-fed rats.

Metabolic syndrome and oxidative stress are common complications of type 2 diabetes mellitus. The present study was designed to determine whether resveratrol, a widely used nutritional supplement, can improve insulin sensitivity, metabolic complication as well as hepatic oxidative stress in fructose-fed rats. Male Sprague Dawley rats (180-200 g) were divided into four groups with 8 animals each. Fructose-fed insulin resistant group (Dia) animals were fed 65% fructose (Research diet, USA) for a period of 8 weeks, whereas control group (Con) animals were fed 65% cornstarch (Research Diet, USA). Resveratrol, 10 mg/kg/day (Dia+Resv) or metformin 300 mg/kg/day (Dia+Met) were administered orally to the 65% fructose-fed rats for 8 weeks. At the end of the feeding schedule, Dia group had insulin resistance along with increased blood glucose, triglyceride, uric acid and nitric oxide (NO) levels. Significant (p<0.05) increase in hepatic TBARS and conjugated dienes, and significant (p<0.05) decrease in hepatic SOD and vitamin C was observed in Dia group compared to Con group. Administration of metformin or resveratrol significantly (p<0.05) normalized all the altered metabolic parameters. However, a marked insulin sensitizing action was only observed in the Dia+Resv group. Similarly, while metformin administration failed to normalize the increased TBARS levels and decreased SOD activity, resveratrol showed a more promising effect of all oxidative stress parameters measured in the present study. Attenuation of hepatic oxidative stress in fructose-fed rat liver after resveratrol administration was associated with significant (p<0.05) increase in nuclear level of NRF2 compared with other groups. The present study demonstrates that resveratrol is more effective than metformin in improving insulin sensitivity, and attenuating metabolic syndrome and hepatic oxidative stress in fructose-fed rats.

In vitro exposure to fullerene C(60) influences redox state and lipid peroxidation in brain and gills from Cyprinus carpio (Cyprinidae).

Studies concerning the impact of nanomaterials, especially fullerene (C(60) ), in fresh water environments and their effects on the physiology of aquatic organisms are still scarce and conflicting. We aimed to assess in vitro effects of fullerene in brain and gill homogenates of carp Cyprinus carpio, evaluating redox parameters. A fullerene suspension was prepared by continued stirring under fluorescent light during two months. The suspension concentration was measured by total carbon content and ultraviolet-visible spectroscopy nephelometry. Characterization of C(60) aggregates was performed with an enhanced dark-field microscopy system and transmission electronic microscopy. Organ homogenates were exposed during 1, 2, and 4 h under fluorescent light. Redox parameters evaluated were reduced glutathione and oxidized glutathione, cysteine and cystine, total antioxidant capacity; activity of the antioxidant enzymes glutathione S-transferase and glutathione reductase (GR), and lipid peroxidation (TBARS assay). Fullerene induced a significant increase (p < 0.05) in lipid peroxidation after 2 h in both organs and reduced GR activity after 1 h (gills) and 4 h (brain) and antioxidant capacity after 4 h (brain). Levels of oxidized glutathione increased in the brain at 1 h and decreased at 2 h as well. Given these results, it can be concluded that C(60) can induce redox disruption via thiol/disulfide pathway, leading to oxidative damage (higher TBARS values) and loss of antioxidant competence.

Toxicity and glutathione implication in the effects observed by exposure of the liver fish cell line PLHC-1 to pure cylindrospermopsin.

Cylindrospermopsin (CYN), a cyanotoxin produced by several freshwater cyanobacteria species, has been reported to cause human and animal intoxications. CYN is a potent inhibitor of protein and glutathione synthesis. In order to study these effects, various in vitro models have been used, which are representative of the organs targeted by the toxin. However, studies concerning CYN toxicity to fish species, both in vivo and in vitro, are still very scarce. To our knowledge, this is the first work dealing with the effects of CYN in a fish cell line. In the present work, we tried to test the hypothesis that CYN could be hepatotoxic to fish causing cell damage and oxidative stress, which may lead to pathogenicity. To deal this purpose, PLCH-1 cells, derived from fish liver, were exposed to concentrations that ranged from 0.3 to 40 µg/mL CYN during 24 and 48 h for the cytotoxicity study, and 2, 4 and 8 µg/mL CYN for the oxidative stress assays. The basal cytotoxicity endpoints studied were protein content, neutral red uptake and the tetrazolium salt, MTS, reduction. The biomarkers used for the oxidative stress study were reactive oxygen species (ROS) content, reduced glutathione content and γ-glutamylcysteine synthetase activity. The cytotoxicity endpoints revealed a decrease in the cellular viability in a time and concentration-dependent way. Moreover, when cells were exposed to pure CYN, an increase in the ROS content was observed, being more marked at the higher concentrations used. Finally, the present work shows alterations in GSH content and synthesis due to CYN. Moreover, a relationship between cytotoxic effects and ROS production has been evidenced. The results obtained confirm the alteration on fish liver cells, which should be considered relevant to what it may happen in real scenarios since fish are frequently in contact with this cyanotoxin.