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 chromium supplementation on oxidative stress biomarkers.

Aim: This systematic review and meta-analysis aimed to evaluate the effects of chromium supplementation on oxidative stress biomarkers such as superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPX), malondialdehyde (MDA), total antioxidant status (TAS), thiobarbituric acid reactive substances (TBARS), catalase (CAT), nitric oxide (NO), total antioxidant capacity (TAC) and protein carbonyl. Methods: Relevant studies, published from inception until July 2019, were searched through PubMed/Medline, Scopus, ISI Web of Science, Embase, and Google Scholar. All randomized clinical trials investigating the effect of chromium supplementation on oxidative stress were included. Results: Out of 252 citations, 10 trials that enrolled 595 subjects were included. Chromium supplementation resulted in a significant increase in GSH (WMD: 64.79 mg/dl, 95% CI: 22.43 to 107.15; P=0.003) but no significant change in MDA, TAS, TBARS levels, SOD, CAT levels and GPX. Chromium picolinate supplementation resulted in a significant increase in TAC while failing to have a significant effect on NO. Moreover, both chromium picolinate and chromium dinicocysteinate supplementation reduced protein carbonyl levels. Conclusion: Overall, this meta-analysis demonstrated that chromium supplementation increased GSH without any significant changes in the mean of GPX, MDA, TAS, TBARS, CAT and SOD.

Siolmatra brasiliensis stem extract ameliorates antioxidant defenses and mitigates glycoxidative stress in mice with high-fat diet-induced obesity.

BACKGROUND: Obesity is accompanied by insulin resistance and glucose intolerance, which favor the onset of complications related to oxidative stress. The aim of this study was to investigate the effects and underlying mechanisms of hydroethanolic extract from Siolmatra brasiliensis stems on insulin resistance, glucose intolerance, advanced glycation end product (AGE) formation, and oxidative stress in mice with induced obesity. METHODS: C57BL-6 J mice were fed a high-fat diet for 14 weeks and treated with 125 or 250 mg/kg S. brasiliensis extract during the last 7 weeks. The study assessed glucose tolerance and insulin sensitivity, lipid profile, plasma levels of thiobarbituric acid reactive substances (TBARS, biomarkers of oxidative damage), fluorescent AGEs (biomarkers of advanced glycation), and paraoxonase 1 (PON1) activity (antioxidant enzyme). The activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in the liver and kidneys were also investigated. RESULTS: Siolmatra brasiliensis extract had antiobesogenic effects; improved insulin sensitivity and glucose tolerance; decreased the total plasma cholesterol levels; decreased the levels of glycoxidative stress biomarkers, including AGEs (plasma, liver, kidneys) and TBARS (liver, kidneys); and also improved endogenous antioxidant defenses by increasing the activities of PON1 (plasma), SOD (kidneys), CAT (liver, kidneys), and GSH-Px (kidneys). CONCLUSION: This study expands on our knowledge about the pharmacological properties of S. brasiliensis and substantiates the potential of this plant species to be used as a complementary therapeutic agent to alleviate the metabolic dysfunctions resulting from dyslipidemia and glycoxidative stress.

Oral administration of potato peel extract affects serum blood metabolites, liver function and ameliorating oxidative stress induced in rabbits exposed to cold stress.

This study investigated the effect of potato peel extract (PPE), orally administrated to rabbits, on serum blood metabolites and ameliorating oxidative stress induced by cold stress under Egyptian winter conditions. Twenty-four bucks grouped into three treatments (8 animals per group) were used for the experiment. The animals received 1.5 ml of water orally, containing 0 (PPE0), 25 (PPE25) or 50 (PPE50) mg PPE/kg live weight. Bucks were randomly assigned into three homogenous equal groups according to the level of PPE. Treatments were applied to each animal every two days over a period of three months including one month as an adaptation period. At the 8th week of the experiment, blood samples were collected from each buck and at the end of the experiment, bucks were slaughtered, and some organs were collected and weighed. The PPE improved (p < 0.05) blood total protein, albumin, globulin and glucose. The blood concentration of total lipid, cholesterol, triglyceride, low density lipoprotein and very low-density lipoprotein (were increased (p < 0.02) in PPE rabbits. Furthermore, PPE extract doses decreased (p < 0.001) oxidant thiobarbituric reactive substance (TBARS) in both blood and liver. Other liver and blood antioxidant system enzymes such as catalase, glutathione peroxidase, and superoxide dismutase were improved (p < 0.005) by PPE supplementation. Overall, oral administration of PPE up to 50 mg/kg live weight can have positive effects on rabbit health under cold stress.

Impact of Phytomediated Zinc Oxide Nanoparticles on Growth and Oxidative Stress Response of In Vitro Raised Shoots of Ochradenus arabicus.

Biogenic nanoparticles have potential roles in the growth and development of plants and animals as they are ecofriendly and free of chemical contaminants. In this study, we assessed the effects of phytomediated zinc oxide nanoparticles (ZnONPs) on shoot growth, biochemical markers, and antioxidant system response in Ochradenus arabicus, which is a medicinal plant. The shoot length and fresh and dry weights were found to be higher in groups with 5 and 10 mg/L ZnONPs than in the control. At high concentrations of ZnONPs (50, 100, and 300 mg/L), biomass was decreased in a concentration-dependent manner. The shoot number was observed to be highest at 50 mg/L among all applied concentrations of ZnONPs. The levels of the stress markers proline and TBARS were found to be higher in shoots treated with 100 and 300 mg/L ZnONPs than in the control as well as NP-treated shoots. The levels of antioxidant enzymes were significantly increased at high concentrations of nanoparticles compared with the control. Thus, synthesized phytomediated ZnONPs from shoots of O. arabicus and their application to the same organ of O. arabicus in vitro were found to be effective as a low concentration of nanoparticles promoted shoot growth, resulting in high biomass accumulation. Thus, using green nanotechnology, such endemic plants could be conserved in vitro and multiple shoots could be produced by reducing the phytohormone concentration for multiple uses, such as the production of potential secondary metabolites.

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.

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.

Effect of increased magnesium intake on plasma cholesterol, triglyceride and oxidative stress in alloxan-diabetic rats.

Cardiovascular disorders are the primary causes of morbidity and mortality in patients with diabetes mellitus (DM). Agents that improve lipid profile and reduce oxidative stress have been shown to reduce the ensuing risk factors. In the present study, we investigated whether increased magnesium intake could improve hyperglycaemia, dyslipidaemia, and reduce oxidative stress in alloxan-induced diabetic rats. Male Wistar rats were divided into non-diabetic (ND), diabetic (DM) and diabetic fed on a high magnesium diet (DM-Mg) groups. Plasma concentrations of thiobarbituric acid reactive substances (TBARS) were used as markers of oxidative stress. Plasma levels of ascorbic acid, magnesium and calcium were also determined. Diabetes was induced by injecting alloxan (100 mg/kg B.W). The fasting blood glucose levels were significantly lower in the DM-Mg rats than in the DM rats. Plasma total cholesterol, triglyceride, TBARS levels were significantly higher while plasma HDL-cholesterol, HDL-cholesterol/total cholesterol ratio, ascorbic acid levels were significantly lowered in DM rats compared with the ND rats. Increased intake of magnesium significantly abrogated these alterations. There were no significant differences in the plasma levels of magnesium and calcium between the DM and ND groups. However, plasma levels of magnesium but not calcium were significantly elevated in DM-Mg rats when compared with other groups. In conclusion, these results suggest that diet rich in magnesium could exert cardioprotective effect through reduced plasma total cholesterol, triglyceride, oxidative stress and ameliorated HDL-cholesterol/total cholesterol ratio as well as increased plasma ascorbic acid and magnesium in diabetic rats.

Role of antioxidant systems in induced nutritional pancreatic atrophy in chicken.

One-day-old chicks were reared using diets differing in their vitamin E and/or selenium content. The purpose of this research was to detect any possible imbalance in the antioxidant defense system, which could be related to development of nutritional pancreatic atrophy. Mitochondrial membranes from animals deficient in both nutrients, or just vitamin E, submitted to peroxidizability 'in vitro' had the production of TBARS greatly enhanced. Measurements of the 2-GSH/GSSG ratio suggested that selenium and vitamin E, the latter in higher magnitude, were responsible for maintenance of the reducing capacity of the cell. Enzymatic defense systems against oxidative stress were also studied. The results indicated that the total antioxidant enzymatic activity of pancreatic cells was not sufficient to scavenge all the ROS generated in the nutritionally deficient animals. The present study suggests that nutritional deficiency of selenium and/or vitamin E generates one imbalance between pro-oxidant and antioxidant systems in chicken pancreas, leading to oxidative stress and pancreatic atrophy.

A simple and sensitive method in using the ratios of cholesteryl ester molecular species as indexes of oxidative stress in plasma and lipoprotein fractions.

To develop a simpler method for lipid peroxidation which may replace the classic gold standard of measuring the loss of polyunsaturated fatty acids, we investigated the use of ratios of molecular species of neutral lipids (MSNL) separated by gas chromatography in a single step. We sub-fractionated lipoproteins and subjected each to oxidation. Among different combinations of ratios of MSNL, we found that the ratios of cholesteryl esters (CE) containing C20/C16 (R1) and C18/C16 (R2) decreased most rapidly with increasing Cu2+ concentration and with increasing oxidation time, for all lipoproteins. We suggest that these two CE ratios can be used as oxidative indexes for all lipoproteins and thus for intact plasma. Experimental evidence showed that the oxidative index of whole plasma is the weighted average index of its lipoproteins. This method was validated with thiobarbituric acid method. Normal healthy asymptomatic males had R1 value 0.496 +/- 0.130, and R2 4.674 +/- 0.848, and females had R1 0.535 +/- 0.117 and R2 4.569 +/- 0.733 with no significant gender differences. Both ratios showed low variabilities within each individual. The method was tested to be feasible in monitoring vitamin E supplementation study. This CE-ratio method is concentration independent. It is simple, rapid, and highly reproducible, and, suitable for screening plasma on large scale.

Atividade antioxidante de espécies medicinais da família Piperaceae: Pothomorphe umbellata (L) Miq e Piper regnellii (Miq) CDC / Antioxidant activity species medicinals of Piperaceae family: Pothomorphe umbellata (L) Miq and Piper regnellii (Miq) CDC

As plantas medicinais constituem importantes recurso terapêutico no tratamento da saúde humana, principalmente das nações em desenvolvimento. Servem tanto à conhecida "medicina caseira", que faz parte da cultura popular destes países, como de matéria prima para elaboração de medicamentos fitoterápicos ou extração de compostos químicos farmacologicamente ativos. O presente trabalho estuda duas espécies medicinais da família Piperaceae, conhecida popularmente como pariparoba, e usadas para o tratamento de problemas do fígado: Piper regnellii (Miq.) D.CD. e Pothomorphe umbellata (L.) Miq., esta inscrita na primeira edição da Farmacopéia Brasileira. Foram avaliadas, comparativamente, as capacidades antioxidantes...

Inhibitory effect of lipid hydroperoxide on cholesteryl esterases.

The oral supplement of air-oxidized linoleate hydroperoxide (LHPO) given in a small quantity to rats resulted in an increase in lipid peroxides (LPO) in the plasma and liver, together with the formation of an oxidatively modified low-density lipoprotein (LDL) with a high content of conjugated diene. Both acid and neutral cholesteryl esterases (CEases) were significantly suppressed in mononuclear leukocytes (MNL), liver, and aorta of the LHPO fed-rats. Significant inverse correlation coefficients were observed between two CEases activities and plasma LPO levels. The LDL isolated from the LHPO fed-rats inhibited in vitro both acid and neutral activities most efficiently among LDL derived from the experimental groups and confirmed in vivo oxidative inactivation of the intracellular CEases, possibly by lipid hydroperoxides in LDL through its increased uptake by the cells.