PMID: 

Trends Immunol. 2010 Mar ;31(3):103-9. Epub 2010 Feb 10. PMID: 20153253

Abstract Title: 

The immunobiology of aluminium adjuvants: how do they really work?

Abstract: 

Aluminium adjuvants potentiate the immune response, thereby ensuring the potency and efficacy of typically sparingly available antigen. Their concomitant critical importance in mass vaccination programmes may have prompted recent intense interest in understanding how they work and their safety. Progress in these areas is stymied, however, by a lack of accessible knowledge pertaining to the bioinorganic chemistry of aluminium adjuvants, and, consequently, the inappropriate application and interpretation of experimental models of their mode of action. The objective herein is, therefore, to identify the many ways that aluminium chemistry contributes to the wide and versatile armoury of its adjuvants, such that future research might be guided towards a fuller understanding of their role in human vaccinations.

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PMID: 

J Basic Clin Physiol Pharmacol. 2019 Aug 30 ;30(5). Epub 2019 Aug 30. PMID: 31469651

Abstract Title: 

Modulatory effects of artichoke (Cynara scolymus L.) leaf extract against oxidative stress and hepatic TNF-α gene expression in acute diazinon-induced liver injury in rats.

Abstract: 

Background Diazinon (DZN) causes serious liver damage in both humans and animals. In the present study, the hepatoprotective effects of Cynara scolymus L. leaf extract against DZN-induced liver injury were examined. Methods Forty male rats were divided into five groups. The control group received a normal diet. The DZN group received DZN only (25 mg/kg, po). The DZN + Syl group received DZN (25 mg/kg, po) and silymarin (Syl) (50 mg/kg, po). The DZN + Art group received DZN (25 mg/kg, po) and artichoke (Art) leaf extract (1500 mg/kg, po). The Art group received Art leaf extract only (1500 mg/kg, po). After 15 days, serum tumor necrosis factorα (TNF-α), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lipid profile, protein carbonyl content, serum and hepatic malondialdehyde (MDA), hepatic TNF-α gene expression, hepatic catalase (CAT), superoxide dismutase (SOD), and vitamin C (Vit C) weremeasured and histopathological examination was performed. Results DZN caused a significant elevation in serum ALP, AST, ALT, MDA, TNF-α, protein carbonyl, hepatic MDA, and TNF-α gene expression in the DZN group as opposed to the control group. Also, DZN led to the reduction of hepatic CAT, SOD, and Vit C in the DZN group relative to the control group. The administration of Art extract resulted in not only a significant reduction in serum ALP, AST, ALT, MDA, TNF-α, and protein carbonyl but also an improvement of liver histopathological changes and hepatic CAT and SOD activities as opposed tothe DZN group. Conclusions This study confirmed that Art leaf extract has liver protective effects and causes downregulation of oxidative stress in acute DZN-induced liver injury in rats.

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PMID: 

Complement Med Res. 2019 Sep 4:1-6. Epub 2019 Sep 4. PMID: 31484191

Abstract Title: 

The Effect of Cynara scolymus on Blood Pressure and BMI in Hypertensive Patients: A Randomized, Double-Blind, Placebo-Controlled, Clinical Trial.

Abstract: 

BACKGROUND: Recent studies have suggested that artichoke (Cynara scolymus L.) may reduce certain biochemical blood factors but the efficacy of this plant on blood pressure (BP) has not yet been investigated. In this study, we determined the clinical efficacy of C. scolymuson BP and body mass index (BMI) in hypertensive patients as an adjunctive to captopril for the first time.METHODS: The total phenolic content and gas chromatography-mass spectrometry metabolite profiling in leaves of C. scolymus have been evaluated. A clinical trial was subsequently carried out on 40 patients to determine the effect of C. scolymus on BP and BMI in hypertensive patients. The treatment group received capsules containing C. scolymus(500 mg twice daily) and the placebo group received starch powder for 8 weeks. Systolic blood pressure (SBP), diastolic blood pressure, and BMI were determined before and after the study.RESULTS: A significant improvement of the BMI was seen in the C. scolymus group compared with the placebo group (p = 0.04).CONCLUSIONS: Our findings demonstrated that the consumption of C. scolymus powder as a rich source of phenolic and antioxidant compounds could potentially improve BMI and SBP in hypertensive patients. Therefore, more trials are needed to confirm or reject the antihypertensive impact of artichoke.

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PMID: 

Pharmacol Toxicol. 1996 Mar ;78(3):123-8. PMID: 8882343

Abstract Title: 

Effect of aluminium hydroxide administration on normal mice: tissue distribution and ultrastructural localization of aluminium in liver.

Abstract: 

In order to assess the risk of parenteral aluminium (Al) exposure, we evaluated the effects of intraperitoneal administration of aluminium hydroxide, a compound widely used in medicine. Mice (strain Pzh:SFIS) received intraperitoneally, every two weeks 1 mg Al or 0.1 mg Al for five days a week. Controls received injections of saline. Al concentrations in liver, bone and brain were evaluated by electrothermal atomic absorption spectrometry after exposure to 2 mg, 4 mg, and 6 mg Al. The concentration was the highest in liver and occurred after exposure to only 2 mg Al (265.1 +/- 27.7 mg/kg, 233.5 +/- 28.0 mg/kg). Generally further accumulation was not dose- and treatment-dependent. The only exception was a significant Al increase in the liver after exposure to 6 mg Al, injected 0.1 mg Al five days/week. Development of resorption granulomas was observed in the liver, Al being revealed by Morin fluorescence in constituent macrophages and giant cells. By electron probe X-ray microanalysis, Al was identified predominantly in lysosomes of macrophages and Kupffer cells. In tibia of mice, a dose-dependent Al accumulation was observed. The highest level of Al concentration after the 6 mg treatment was 23.5 +/- 3.82 mg/kg and 25.06 +/- 2.3 mg/kg. The Al concentration in the brain of mice had not changed significantly during Al treatment.

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PMID: 

Arch Physiol Biochem. 2019 Sep 28:1-11. Epub 2019 Sep 28. PMID: 31564131

Abstract Title: 

Effect of Artichoke () on cardiac markers, lipid profile and antioxidants levels in tissue of HFD-induced obesity.

Abstract: 

Obesity plays a pivotal role in the insulin resistance disease, which is related to hypertension, hyperlipidemia, type 2 diabetes mellitus, and an increased risk of cardiovascular disease. The purpose of the present study was done to evaluate the effect of artichoke leaves extract (ALE) in the high-fat diet (HFD)-induced cellular obesity and cardiac damage in Wistar rats. Body and organ weights, serum lipid profile, cardiac markers, and antioxidants enzymes were measured. Oral administration of ALE at two doses 200 and 400 mg/kg for a period of 60 days showed a significant decrease in body and organ weights, serum total cholesterol, triglycerides, LDH, ALT accompanied by decreasing in oxidative stress biomarker (MDA, and AOPP) and increasing antioxidant enzymes (SOD, CAT, and GPx) levels as compared to HFD groups. The histological findings showed a cardioprotective effect of ALE. These findings suggest that ALE exert anti-oxidant cardiac effects in HFD- induced obese rats.

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PMID: 

Rev Environ Health. 1991 Oct-Dec;9(4):191-205. PMID: 1842454

Abstract Title: 

Aluminum ingestion–is it related to dementia?

Abstract: 

Elevated levels of aluminum in brain tissue have been found in demented patients with Alzheimer's disease, with ALS-PD complex of Guam and with dialysis encephalopathy. A possible etiological relationship between enhanced aluminum exposure and impaired mental function was suggested both for ALS-PD of Guam (a region where high contents of aluminum in water are found) and for dialysis encephalopathy which appears in dialyzed patients exposed to high doses of aluminum in medications and in dialysate fluid. The role of aluminum in Alzheimer's disease is not known as is the question of life-long aluminum accumulation in healthy human beings. In this review we have limited ourselves to the issue of oral aluminum ingestion and the possible neurotoxic consequences of such exposure. The following topics are summarized: 1. Physiological mechanisms involved in ingestion and intestinal absorption of aluminum and the influences of pH and available organic complexing agents on these processes. 2. Effects of an aluminum-enriched diet on behavior and on brain metabolism. 3. Dietary sources of aluminum and elevated loads of this substance due to prolonged intake of aluminum-containing medications. The main conclusion of this summary is that aluminum is absorbed and may accumulate in different organs in both adults and infants. Two groups seem to be at particular risk for aluminum related toxicity: people with chronic renal failure treated with aluminum-containing medications and pre-term infants fed on aluminum containing formulate. It seems probable that at least upon short term exposure the healthy human body can defend itself adequately from aluminum's toxic effects. However, not enough information is available on possible effects of life-long exposure to aluminum in the environment, diet and medications, which over decades may lead to accumulation of this substance with expressions of toxicity. Therefore, the question of aluminum's relevance to dementive diseases cannot yet be adequately answered.

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PMID: 

Environ Health Perspect. 1979 Jun ;30:47-51. PMID: 446457

Abstract Title: 

Experimental study of biological effects of leads and aluminum following oral administration.

Abstract: 

A wide spectrum of the biological effects of lead and aluminum ions is noted during short-term and long-term oral administration to laboratory animals. The general toxic and gonadotoxic effects of these metals during a short-term experiment appeared to be identical, and the correlation of these effects was preserved during chronic experiments. Lead (0.03 mg/l.) and aluminum (0.5 mg/l.) concentrations in water may be dangerous to the health of the population, and hygienic standards are recommended for inclusion in the standard for drinking water quality.

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PMID: 

Hum Vaccin Immunother. 2015 ;11(2):477-88. PMID: 25692535

Abstract Title: 

Advances in aluminum hydroxide-based adjuvant research and its mechanism.

Abstract: 

In the past few decades, hundreds of materials have been tried as adjuvant; however, only aluminum-based adjuvants continue to be used widely in the world. Aluminum hydroxide, aluminum phosphate and alum constitute the main forms of aluminum used as adjuvants. Among these, aluminum hydroxide is the most commonly used chemical as adjuvant. In spite of its wide spread use, surprisingly, the mechanism of how aluminum hydroxide-based adjuvants exert their beneficial effects is still not fully understood. Current explanations for the mode of action of aluminum hydroxide-based adjuvants include, among others, the repository effect, pro-phagocytic effect, and activation of the pro-inflammatory NLRP3 pathway. These collectively galvanize innate as well as acquired immune responses and activate the complement system. Factors that have a profound influence on responses evoked by aluminum hydroxide-based adjuvant applications include adsorption rate, strength of the adsorption, size and uniformity of aluminum hydroxide particles, dosage of adjuvant, and the nature of antigens. Although vaccines containing aluminum hydroxide-based adjuvants are beneficial, sometimes they cause adverse reactions. Further, these vaccines cannot be stored frozen. Until recently, aluminum hydroxide-based adjuvants were known to preferentially prime Th2-type immune responses. However, results of more recent studies show that depending on the vaccination route, aluminum hydroxide-based adjuvants can enhance both Th1 as well as Th2 cellular responses. Advances in systems biology have opened up new avenues for studying mechanisms of aluminum hydroxide-based adjuvants. These will assist in scaling new frontiers in aluminum hydroxide-based adjuvant research that include improvement of formulations, use of nanoparticles of aluminum hydroxide and development of composite adjuvants.

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PMID: 

Environ Sci Eur. 2017 ;29(1):19. Epub 2017 Apr 12. PMID: 28458989

Abstract Title: 

Migration of aluminum from food contact materials to food-a health risk for consumers? Part I of III: exposure to aluminum, release of aluminum, tolerable weekly intake (TWI), toxicological effects of aluminum, study design, and methods.

Abstract: 

BACKGROUND: In spite of the prevalence of aluminum in nature, no organism has been found to date which requires this element for its biological functions. The possible health risks to human beings resulting from uptake of aluminum include detrimental effects to the hemopoietic system, the nervous system and bones. Aluminum is used in many fields and occurs in numerous foodstuffs. Food contact materials containing aluminum represent an anthropogenic source of dietary aluminum.RESULTS: As a result of their frequent use in private households a study was undertaken to detect migration of this metal to foodstuffs from drink containers, coffee pots, grill pans, and camping cookware made of aluminum.CONCLUSIONS: An estimate of the health risk to consumers is calculated, based on the tolerable weekly intake (TWI) specified by the European Food Safety Authority of 1 mg/kg body weight for all groups of people. In some instances the TWI is significantly exceeded, dependent upon the food contact material and the food itself.

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PMID: 

Neurotoxicology. 2000 Oct ;21(5):813-28. PMID: 11130287

Abstract Title: 

The toxicology of aluminum in the brain: a review.

Abstract: 

Aluminum is environmentally ubiquitous, providing human exposure. Usual human exposure is primarily dietary. The potential for significant Al absorption from the nasal cavity and direct distribution into the brain should be further investigated. Decreased renal function increases human risk of Al-induced accumulation and toxicity. Brain Al entry from blood may involve transferrin-receptor mediated endocytosis and a more rapid process transporting small molecular weight Al species. There appears to be Al efflux from the brain, probably as Al citrate. There is prolonged retention of a fraction of Al that enters the brain, suggesting the potential for accumulation with repeated exposure. Al is a neurotoxicant in animals and humans. It has been implicated in the etiology of sporadic Alzheimer's disease (AD) and other neurodegenerative disorders, although this is highly controversial. This controversy has not been resolved by epidemiological studies, as only some found a small association between increased incidence of dementia and drinking water Al concentration. Studies of brain Al in AD have not produced consistent findings and have not resolved the controversy. Injections of Al to animals produce behavioral, neuropathological and neurochemical changes that partially model AD. Aluminum has the ability to produce neurotoxicity by many mechanisms. Excess, insoluble amyloid beta protein (A beta) contributes to AD. Aluminum promotes formation and accumulation of insoluble A beta and hyperphosphorylated tau. To some extent, Al mimics the deficit of cortical cholinergic neurotransmission seen in AD. Al increases Fe-induced oxidative injury. The toxicity of Al to plants, aquatic life and humans may share common mechanisms, including disruption of the inositol phosphate system and Ca regulation. Facilitation of Fe-induced oxidative injury and disruption of basic cell processes may mediate primary molecular mechanisms of Al-induced neurotoxicity. Avoidance of Al exposure, when practical, seems prudent.

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