The effects of spirulina on glycemic control and serum lipoproteins in patients with metabolic syndrome and related disorders.

PMID: 

Phytother Res. 2019 Jul 29. Epub 2019 Jul 29. PMID: 31359513

Abstract Title: 

The effects of spirulina on glycemic control and serum lipoproteins in patients with metabolic syndrome and related disorders: A systematic review and meta-analysis of randomized controlled trials.

Abstract: 

The aim of this systematic review and meta-analysis was to evaluate the effects of spirulina on glycemic control and serum lipoproteins in patients with metabolic syndrome (MetS) and related disorders. Two independent authors systematically searched online database including EMBASE, Scopus, PubMed, Cochrane Library, and Web of Science from inception until April 30, 2019. The Cochrane Collaboration's risk of bias tool was applied to assess the methodological quality of included trials. The heterogeneity among the included studies was assessed using Cochrane's Q test and I-square (I) statistic. Pooling effect sizes from studies showed a significant reduction in fasting plasma glucose (FPG; weighted mean difference [WMD]: -10.31; 95% confidence interval, CI [-16.21, -4.42]) and insulin concentrations (WMD: -0.53; 95% CI [-0.62, -0.44]) following the administration of spirulina. Pooled analysis showed also a significant reduction in total cholesterol (WMD: -20.50; 95% CI [-38.25, -2.74]), low-density lipoprotein cholesterol (LDL-C; WMD: -19.02; 95% CI [-36.27, -1.78]), and very low-density lipoprotein cholesterol (VLDL-C) concentrations (WMD: -6.72; 95% CI [-9.19, -4.26]) and a significant increase in high-density lipoprotein cholesterol (HDL-C) levels (WMD: 1.42; 95% CI [0.16, 2.68]) following spirulina therapy. This meta-analysis demonstrated the beneficial effects of spirulina supplementation on improving FPG, insulin, total cholesterol, LDL-C, VLDL-C, and HDL-C levels in patients with MetS and related disorders.

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Role of Spirulina in mitigating hemato-toxicity in Swiss albino mice exposed to aluminum and aluminum fluoride.

PMID: 

Environ Sci Pollut Res Int. 2016 Dec ;23(24):25280-25287. Epub 2016 Sep 29. PMID: 27687764

Abstract Title: 

Role of Spirulina in mitigating hemato-toxicity in Swiss albino mice exposed to aluminum and aluminum fluoride.

Abstract: 

Aluminum is ingested through foods, water, air, and even drugs. Its intake is potentiated further through foods and tea prepared in aluminum utensils and Al salt added in the drinking water for removal of suspended impurities and also fluoride in the affected areas. The ameliorating role of a blue green alga Spirulina is well documented to various pollutants in the animal models. We, therefore, examined its protective role (230 mg/kg body weight) on the hematology of male Swiss albino mice treated with aluminum (sub-acute = 78.4 mg/kg body weight for 7 days, sub-chronic = 7.8 mg/kg body weight for 90 days) and aluminum fluoride (sub-acute = 103 mg/kg body weight, sub-chronic = 21 mg/kg body weight), along with their recovery after 90 days of sub-chronic exposure. This study revealed significant reduction in the values of RBC (5-18 %), Hb (15-17 %), PCV (8-14 %), and platelets (26-36 %), and increase in WBC (54-124 %) in the treated mice, particularly after sub-acute exposure. Aluminum fluoride was comparatively more toxic than aluminum. Further, Spirulina supplement not only alleviated toxicity of test chemicals in Swiss albino mice but also led to their better recovery after withdrawal.

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Aluminium in foodstuff and the influence of aluminium foil used for food preparation or short time storage.

PMID: 

Food Addit Contam Part B Surveill. 2018 Jun ;11(2):153-159. Epub 2018 Mar 16. PMID: 29486656

Abstract Title: 

Aluminium in foodstuff and the influence of aluminium foil used for food preparation or short time storage.

Abstract: 

Aluminium is an omnipresent part of everyday life. It is widely used in industry and furthermore in products like cosmetics, sun creams or it can be applied for instance as aluminium foil by consumers during food preparation in households. However, over the last decades the toxicity of aluminium for humans has been heavily discussed and is still not completely clarified. Therefore, food aluminium concentrations were investigated in different untreated foodstuff as well as a possible aluminium transfer from aluminium foil to food. The results show that untreated food is not significantly contaminated. Furthermore, short time contact to aluminium foil increases the food aluminium concentration only marginally. Nevertheless, as soon as the food is in contact to aluminium foil and at the same time in contact with metals (alloys) with a higher standard electrode potential than aluminium (-1.66 V) high aluminium contaminations were observed.

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The use of aluminum utensils for cooking meals is associated with chronic aluminum toxicity.

PMID: 

J Assoc Physicians India. 2019 Apr ;67(4):52-56. PMID: 31309799

Abstract Title: 

 Relationship between the Use of Aluminium Utensils for Cooking Meals and Chronic Aluminum Toxicity in Patients on Maintenance Hemodialysis: A Case Control Study.

Abstract: 

Background: Chronic aluminum toxicity (CAT) in end stage kidney disease (ESKD) patients is now a rare clinical disorder, unlike in the past, because of improvements in hemodialysis water purification systems and discontinuation of use of aluminum hydroxide as a phosphate binder. The use of aluminum utensils for cooking could be an unrecognised cause of the CAT.Objective: To assess the association between aluminum kitchen utensils used for cooking meals and chronic aluminum toxicity (CAT) in patients on maintenance hemodialysis (MHD).Material and Methods: In this case control study, a total of 31 (cases n=10; controls n=21) patients on MHD for more than one year were included. Cases were defined as patients with clinical manifestations (including laboratory parameters) of CAT and high (>200 mcg/L) serum aluminum levels. Control group was chosen from the same hemodialysis facilities. Association between use of aluminum utensils for cooking and occurrence of CAT was assessed.Results: The mean age of patients in the cases and the control group was 52.90 and 52.95 years respectively with on significant difference (p=0.99). There was no difference in mean duration of dialysis (p=0.78), serum calcium level (p=0.06), serum phosphate level (p=0.19), serum albumin level (p=0.06), history of hypertension (p=1.00) and history of diabetes (n=0.12) between two groups. Mean haemoglobin (p

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Antioxidant, anti-inflammatory, and postulated cytotoxic activity of phenolic and anthocyanin-rich fractions from raspberry.

PMID: 

Molecules. 2018 Jul 21 ;23(7). Epub 2018 Jul 21. PMID: 30037097

Abstract Title: 

Antioxidant, Anti-Inflammatory, and Postulated Cytotoxic Activity of Phenolic and Anthocyanin-Rich Fractions from Polana Raspberry (L.) Fruit and Juice-In Vitro Study.

Abstract: 

In this study, the antioxidative and anti-inflammatory potential of crude extracts (CE), anthocyanin-rich fractions (ARF), and phenolic fractions (PF) from raspberry (R) and raspberry juice (J) were evaluated. The antioxidant properties were evaluated with three complementary assays: DPPH radical scavenging activity, chelating Fe(II) power, and ferric reducing power. The highest antioxidant activity was determined for the crude extract from raspberry pulp (RCE) in the case of all methods used. The anti-inflammatory activity was demonstrated by inhibitory effect on lipoxygenase (LOX) and cyclooxygenase-2 (COX-2) activity in vitro. The highest efficiency in inhibiting the activity of both enzymes was exhibited by RCE, 0.79 and 0.59 mg FW/mL, respectively. In turn, JARF had the lowest ability to inhibit LOX (EC50 = 4.5 mg FW/mL) and JPF caused the lowest COX-2 inhibition (1.75 mg FW/mL). Additionally, we have performed a pilot study of in vitro cytotoxic activity using two human leukemia cell lines: J45 and HL60. All examined extracts inhibited the viability of J45 cells more effectively than HL60. The highest cytotoxic effect was observed in the J45.01 cell line after exposure to RCE (EC50 = 0.0375 mg FW/mL).

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Fresh red raspberry phytochemicals suppress the growth of hepatocellular carcinoma cells by PTEN/AKT pathway.

PMID: 

Int J Biochem Cell Biol. 2018 11 ;104:55-65. Epub 2018 Sep 5. PMID: 30195065

Abstract Title: 

Fresh red raspberry phytochemicals suppress the growth of hepatocellular carcinoma cells by PTEN/AKT pathway.

Abstract: 

The red raspberry (Rubus idaeus L.) is a common fruit worldwide and its extract has been found to inhibit the growth of many types of tumors, mainly because it is rich in bioactive phytochemicals. However, the mechanism underlying its anticancer activity in hepatocellular carcinoma (HCC) is not well understood. Herein, the aim of this study was to determine the effects of red raspberry phytochemicals on the proliferation of hepatocellular carcinoma cells and to elucidate its biochemical and molecular targets. CCK8 and colony formation, as well as flow cytometry assays, were employed to determine the effects of red raspberry extract (RRE) on cell proliferation and cell cycle distribution in HCC cells. Our results showed that RRE significantly inhibited cell proliferation and arrested cell cycle progression at the S phase in HCC cells. RRE increased the expression of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) by reducing the methylation status of the PTEN gene promoter and inhibiting DNMT1 expression and regulated AKT signaling pathway. These findings show that red raspberry phytochemicals inhibit the proliferation of HCC cells by regulating PTEN/AKT signaling pathway, providing evidence that RRE may be used as a potential auxiliary therapy for patients with HCC.

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Thimerosal dose-dependently inhibits ER aminopeptidase 1, an important enzyme for the human adaptive immune response.

PMID: 

ACS Med Chem Lett. 2016 Jul 14 ;7(7):681-5. Epub 2016 May 31. PMID: 27437077

Abstract Title: 

Screening Identifies Thimerosal as a Selective Inhibitor of Endoplasmic Reticulum Aminopeptidase 1.

Abstract: 

We employed virtual screening followed by in vitro evaluation to discover novel inhibitors of ER aminopeptidase 1, an important enzyme for the human adaptive immune response that has emerged as an attractive target for cancer immunotherapy and the control of autoimmunity. Screening hits included three structurally related compounds carrying the (E)-N'-((1H-indol-3-yl)methylene)-1H-pyrazole-5-carbohydrazide scaffold and (2-carboxylatophenyl)sulfanyl-ethylmercury as novel ERAP1 inhibitors. The latter, also known as thimerosal, a common component in vaccines, was found to inhibit ERAP1 in the submicromolar range and to present strong selectivity versus the homologous aminopeptidases ERAP2 and IRAP. Cell-based analysis indicated that thimerosal can effectively reduce ERAP1-dependent cross-presentation by dendritic cells in a dose-dependent manner.

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Thimerosal depresses neuronal excitability in rat neurons.

PMID: 

Brain Res. 2000 May 2 ;864(1):105-13. PMID: 10793192

Abstract Title: 

Inhibitory action of thimerosal, a sulfhydryl oxidant, on sodium channels in rat sensory neurons.

Abstract: 

The effects of thimerosal, a sulfhydryl oxidizing agent, on tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) sodium channels in rat dorsal root ganglion neurons were studied using the whole-cell patch clamp technique. Thimerosal blocked the two types of sodium channels in a dose-dependent manner. The inhibitory effect of thimerosal was much more pronounced in TTX-R sodium channels than TTX-S sodium channels. The effect of thimerosal was irreversible upon wash-out with thimerosal-free external solution. However, dithiothreitol, a reducing agent, partially reversed it. Thimerosal shifted the steady-state inactivation curves for both types of sodium channels in the hyperpolarizing direction. The voltage dependence of activation of both types of sodium channels was shifted in the depolarizing direction by thimerosal. The inactivation rate in both types of sodium channels increased after thimerosal treatment. All these effects of thimerosal would add up to cause a depression of sodium channel function leading to a diminished neuronal excitability.

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This review proposes a possibly link between maternal obesity, mercury levels, and autism in offspring.

PMID: 

Med Hypotheses. 2016 Jun ;91:90-94. Epub 2016 Apr 15. PMID: 27142153

Abstract Title: 

Mercury as a possible link between maternal obesity and autism spectrum disorder.

Abstract: 

The incidence of both obesity and autism spectrum disorders (ASD) has dramatically increased during the last decades. Moreover, the most recent studies have revealed increased risk of ASD in offspring of overweight and obese women. However, the mechanisms of association between ASD and maternal obesity are unknown. Taking into account the existing data indicating the association between mercury (Hg) exposure and development of obesity and ASD, we hypothesize that Hg may serve as an additional link between maternal obesity and ASD. In particular, it is supposed that obesity is associated with excessive accumulation of Hg in the maternal organism. After conception, the fetus is developing in the conditions of Hg overload within the body of obese women thus predisposing to the development of ASD. The proposed hypothesis may be confirmed by the existing data. In particular, previous studies demonstrated that overweight and obese persons are characterized by a significantly higher level of Hg in hair, blood and urine than the lean ones. Therefore, an obese organism is characterized by elevated Hg burden that may be transferred to the fetus during pregnancy. Moreover, multiple studies have demonstrated a tight association between maternal and children Hg status being indicative of placental transfer of metal from maternal organism to offspring. Finally, a growing body of data indicates the influence of Hg exposure and Hg status on the risk of ASD in children. However, additional experimental and clinical studies are required to prove the hypothesis and provide novel data on the role of Hg in maternal obesity-associated ASD development. In particular, the contribution of Hg to ASD development in children from obese mothers should be determined. If a significant role of Hg in maternal obesity ASD risk will be confirmed, this will open additional perspectives of risk modification. Taking into account the universal mechanisms of Hg toxicity, transport, and accumulation, further preventive actions may be undertaken to reduce the risk of Hg toxicity and Hg-associated ASD development. In particular, it is supposed that the use of Hg chelators (like N,N'bis-(2-mercaptoethyl)isophthalamide, NMBI), antioxidants, and anti-inflammatory compounds prior or during pregnancy may have a beneficial effect. However, the safety of such actions should repeatedly be tested to avoid adverse health effects in a developing fetus.

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This study demonstrates that there are sex-and structure-specific changes to thioredoxin system antioxidant systems responses in methylmercury neurotoxicity.

PMID: 

Neurotoxicology. 2016 09 ;56:118-126. Epub 2016 Jul 22. PMID: 27456245

Abstract Title: 

Sex- and structure-specific differences in antioxidant responses to methylmercury during early development.

Abstract: 

Methylmercury (MeHg) is a ubiquitous environmental contaminant and neurotoxin, particularly hazardous to developing and young individuals. MeHg neurotoxicity during early development has been shown to be sex-dependent via disturbances in redox homeostasis, a key event mediating MeHg neurotoxicity. Therefore, we investigated if MeHg-induced changes in key systems of antioxidant defense are sex-dependent. C57BL/6J mice were exposed to MeHg during the gestational and lactational periods, modeling human prenatal and neonatal exposure routes. Dams were exposed to 5ppm MeHg via drinking water from early gestational period until postnatal day 21 (PND21). On PND21 a pair of siblings (a female and a male) from multiple (5-6) litters were euthanized and tissue samples were taken for analysis. Cytoplasmic and nuclear extracts were isolated from fresh cerebrum and cerebellum and used to determine thioredoxin (Trx) and glutathione (GSH) levels, as well as thioredoxin reductase (TrxR) and glutathione peroxidase (GPx) activities. The remaining tissue was used for mRNA analysis. MeHg-induced antioxidant response was not uniform for all the analyzed antioxidant molecules, and sexual dimorphism in response to MeHg treatment was evident for TrxR, Trx and GPx. The pattern of response, namely a decrease in males and an increase in females, may impart differential and sex-specific susceptibility to MeHg. GSH levels were unchanged in MeHg treated animals and irrespective of sex. Trx was reduced only in nuclear extracts from male cerebella, exemplifying a structure-specific response. Results from the gene expression analysis suggest posttranscriptional mechanism of sex-specific regulation of the antioxidant response upon MeHg treatment. The study demonstrates for the first time sex-and structure-specific changes in the response of the thioredoxin system to MeHg neurotoxicity and suggests that these differences in antioxidant responses might impart differential susceptibility to developmental MeHg exposure.

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