A comprehensive review on medicinal plants possessing antioxidant potential.

Many research studies have proposed that about two-thirds of the medicinal plant species of the world possess significant antioxidant potential. Antioxidants are very beneficial as they decrease oxidative stress (OS) in cells and hence play their role in management as well as treatment of numerous diseases like cancers, cardiovascular diseases, as well as many inflammatory illnesses. This review comprises the antioxidant potential of numerous parts of medicinal plants like leaves, stems, roots, seeds, fruits, as well as bark. Synthetic antioxidants named butylated hydroxyanisole (BHA) as well as butylated hydroxytoluene (BHT) are extensively employed in foods because of their role as food preservatives. Several natural antioxidants have better efficacy as compared to synthetic antioxidants. These medicinal plants include Geranium sanguineum L., Rheum ribes L., Diospyros abyssinica, Sargentodoxa cuneata Rehd. Et Wils, Pistacia lentiscus, Ficus microcarpa L. fil., Polyalthia cerasoides (Roxb.) Bedd, Cunn, Teucrium polium L., Crataeva nurvala Buch-Ham., Urtica dioica L., Dracocephalum moldavica L., Momordica Charantia L., Acacia auriculiformis A., Bidens pilosa Linn. The Lamiaceae species, Radiata, Leea indica, Pelargonium endlicherianum, Salvia officinalis L., and Uncaria tomentosa (Willd.) DC. The literature study disclosed more side effects of synthetic antioxidants (including food additives) in comparison with natural antioxidants and for prevention of many diseases.

The Role of Cell Proliferation and Extracellular Matrix Accumulation Induced by Food Additive Butylated Hydroxytoluene in Uterine Leiomyoma.

Leiomyoma is the most common benign uterine tumor in reproductive-age women. Increasing numbers of studies are focusing on the effects of environmental exposure on the incidence and progression of tumors. One major step taken in the food industry is the addition of food preservatives to maintain freshness. Butylated hydroxytoluene (BHT) is a synthetic phenolic antioxidant, which is widely used as an additive to develop fat-soluble characteristics, as well as in cosmetics and rubber. Previous studies also highlighted that BHT may be related to increased fibrosis capacity and carcinogenic effects. In this study, we explored the effects of the commonly used food additive BHT on leiomyoma progression, and the related mechanism. The exposure of the ELT-3 leiomyoma cell line to BHT for 48 h increased the proliferative effect. Since leiomyoma progression is related to increases in extracellular matrix (ECM) accumulation and matrix metalloproteinase (MMP), BHT could effectively increase ECM-related protein expression, as well as MMP-2 and MMP-9 protein expression. This increase in ECM, in response to BHT, may be linked to the activation of the phosphoinositide 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK) signaling pathway. Through PI3K inhibition, BHT's effect on leiomyoma progression could be partially modulated. These results suggest the harmful effect of BHT exposure on leiomyoma progression may relate to PI3K modulation. However, an in vivo study is necessary to confirm these findings.

Changes in adhesive ingredients in continuous glucose monitoring systems may induce new contact allergy pattern.

BACKGROUND: Medical devices (MD) in close skin-contact for a prolonged time, such as glucose monitoring (CGM) systems, are a risk factor for contact allergy, and there has been an increase in patients using these. Correct diagnosis demands targetted testing. OBJECTIVES: We report a new allergen in a continuous CGM system in which the adhesive was changed. The allergy pattern of the patients diagnosed is reported. METHODS: The three patients reported were patch tested with an MD series, own material, and possible allergens found through analysis with gas chromatography-mass spectrometry, comparing analysis from the CGM system before and after change. RESULTS: The patients were sensitized to isobornyl acrylate (IBOA), found in previously used devices and the present CGM. Apart from IBOA, the culprit allergen was found to be 2,2'-methylenebis(6-tert-butyl-4-methylphenol) monoacrylate. CONCLUSION: Allergic contact dermatitis due to CGM systems and insulin pumps are difficult to investigate and require chemical analysis. Because of the lack of information on substances used in the production, and when changes with MDs are initiated, it is difficult to advise patients, especially since they risk sensitization to several allergens. The use of MDs has increased and, thus, the need for collaboration between manufacturers, clinicians, and patient organizations.

Phenolic antioxidant 2,6-di-tert-butyl-p-cresol (vitamin E synthetic analogue) does not inhibit 1,1'-dimetyl-4,4'-bipyridium dichloride (paraquat)-induced structural chromosomal damage in cultured leukocytes of the dark-spotted-frog Pelophylax (Rana) nigromaculatus.

Pro-oxidative effect of phenolic antioxidant (vitamin E) in combination with the initiators on human low-density lipoprotein is known. Recently I reported that oxidative stress induced by vitamin E in combination with the herbicide paraquat enhances structural chromosomal damage in cultured anuran leukocytes. In the present study, the phenolic antioxidant vitamin E-synthetic-analogue 2,6-di-tert-butyl-p-cresol (BHT) in combination with paraquat was found to enhance structural chromosomal damage in cultured Pelophylax (Rana) nigromaculatus leukocytes more than paraquat only and paraquat plus nicotinamido adenine dinucleotido phosphate served as positive control, although BHT only had no effect on induction of structural chromosomal damage. Paraquat plus BHT-enhanced structural chromosomal damage was inhibited by combination of the superoxide dismutase mimic Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin and the hydrogen peroxide scavenger catalase. In test based on reduction of paraquat cation, BHT was found to reduce paraquat cation chemically to paraquat monocation radical. These results suggest that BHT functions in chemically donating electron to paraquat and thereby induces an acute accumulation of reactive oxygen species, resulting in increase in chromosomal damage.

Sensibilización por galatos. Revisión de 46 casos / Sensitization to gallates: review of 46 cases

Introducción. Los galatos son antioxidantes empleados en la industria cosmética, farmacéutica y alimentaria desde 1947, con la finalidad de evitar la oxidación de los ácidos grasos insaturados que contienen estos productos. El objetivo de este trabajo es revisar los casos de sensibilización por galatos diagnosticados en nuestro Servicio entre 1985 y 2006. Métodos. Se han extraído de la base de datos de la Sección de Alergia de nuestro Servicio todos los casos investigados por sospecha de dermatitis alérgica de contacto, que presentaron pruebas epicutáneas positivas al propil galato, octil galato y/o dodecil galato. Resultados. Cuarenta y seis pacientes presentaron uno o más parches positivos a los galatos (36 mujeres y 10 varones, con una edad media de 42,8 años). El motivo de consulta más frecuente fue la queilitis (63 % de los casos) seguido de la dermatitis de las manos (28,26 % de los casos). El origen más frecuente de la sensibilización fue el uso de barras labiales (54,3 % de los casos), seguido de la manipulación de productos de panadería (15,2 % de los casos). La relevancia de los resultados se consideró presente en el 73,9 % de los casos y desconocida en el 23,9 % de los pacientes. Conclusiones. En nuestra serie la mayoría de los pacientes sensibilizados a los galatos consultaron por queilitis, el principal alérgeno responsable fue el propil galato, y el mecanismo más frecuente de sensibilización fue el uso de barras labiales. El galato más frecuente en los panaderos fue el octil galato, con relevancia presente en todos los casos estudiados

Background. Since 1947, the cosmetics, pharmaceutical, and food industries have used gallates as antioxidants to prevent the oxidation of unsaturated fats in their products. The aim of this study was to review the cases of sensitization to gallates diagnosed in our department between 1985 and 2006. Methods. All suspected cases of allergic contact dermatitis with patch tests positive for propyl gallate, octyl gallate, and/or dodecyl gallate were retrieved from the database of the allergy section of our dermatology department. Results. Forty-six patients had positive patch tests for 1 or more gallates (36 women and 10 men, with a mean age of 42.8 years). The most common presenting complaint was cheilitis (63 % of the cases) followed by dermatitis of the hands (28.26 %). The most common sensitizing agent was lipstick (54.3 %) followed by bakery products (15.2 %). The test result was considered clinically relevant in 73.9 % of the cases whereas the relevance was unknown in 23.9 %. Conclusions. In our case series, most patients sensitized to gallates attended the clinic due to cheilitis. The main allergen was propyl gallate and the most common mechanism of sensitization was use of lipstick. The most common gallate among bakers was octyl gallate. This agent was considered to be clinically relevant in all cases studied

Final report on the safety assessment of BHT(1).

BHT is the recognized name in the cosmetics industry for butylated hydroxytoluene. BHT is used in a wide range of cosmetic formulations as an antioxidant at concentrations from 0.0002% to 0.5%. BHT does penetrate the skin, but the relatively low amount absorbed remains primarily in the skin. Oral studies demonstrate that BHT is metabolized. The major metabolites appear as the carboxylic acid of BHT and its glucuronide in urine. At acute doses of 0.5 to 1.0 g/kg, some renal and hepatic damage was seen in male rats. Short-term repeated exposure to comparable doses produced hepatic toxic effects in male and female rats. Subchronic feeding and intraperitoneal studies in rats with BHT at lower doses produced increased liver weight, and decreased activity of several hepatic enzymes. In addition to liver and kidney effects, BHT applied to the skin was associated with toxic effects in lung tissue. BHT was not a reproductive or developmental toxin in animals. BHT has been found to enhance and to inhibit the humoral immune response in animals. BHT itself was not generally considered genotoxic, although it did modify the genotoxicity of other agents. BHT has been associated with hepatocellular and pulmonary adenomas in animals, but was not considered carcinogenic and actually was associated with a decreased incidence of neoplasms. BHT has been shown to have tumor promotion effects, to be anticarcinogenic, and to have no effect on other carcinogenic agents, depending on the target organ, exposure parameters, the carcinogen, and the animal tested. Various mechanism studies suggested that BHT toxicity is related to an electrophillic metabolite. In a predictive clinical test, 100% BHT was a mild irritant and a moderate sensitizer. In provocative skin tests, BHT (in the 1% to 2% concentration range) produced positive reactions in a small number of patients. Clinical testing did not find any depigmentation associated with dermal exposure to BHT, although a few case reports of depigmentation were found. The Cosmetic Ingredient Review Expert Panel recognized that oral exposure to BHT was associated with toxic effects in some studies and was negative in others. BHT applied to the skin, however, appears to remain in the skin or pass through only slowly and does not produce systemic exposures to BHT or its metabolites seen with oral exposures. Although there were only limited studies that evaluated the effect of BHT on the skin, the available studies, along with the case literature, demonstrate no significant irritation, sensitization, or photosensitization. Recognizing the low concentration at which this ingredient is currently used in cosmetic formulations, it was concluded that BHT is safe as used in cosmetic formulations.

Intake of butylated hydroxyanisole and butylated hydroxytoluene and stomach cancer risk: results from analyses in the Netherlands Cohort Study.

Both carcinogenic and anticarcinogenic properties have been reported for the synthetic antioxidants butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT). The association between dietary intake of BHA and BHT and stomach cancer risk was investigated in the Netherlands Cohort Study (NLCS) that started in 1986 among 120,852 men and women aged 55 to 69 years. A semi-quantitative food frequency questionnaire was used to assess food consumption. Information on BHA or BHT content of cooking fats, oils, mayonnaise and other creamy salad dressings and dried soups was obtained by chemical analysis, a Dutch database of food additives (ALBA) and the Dutch Compendium of Foods and Diet Products. After 6.3 years of follow-up, complete data on BHA and BHT intake of 192 incident stomach cancer cases and 2035 subcohort members were available for case-cohort analysis. Mean intake of BHA or BHT among subcohort members was 105 and 351 microg/day, respectively. For consumption of mayonnaise and other creamy salad dressings with BHA or BHT no association with stomach cancer risk was observed. A statistically non-significant decrease in stomach cancer risk was observed with increasing BHA and BHT intake [rate ratio (RR) highest/lowest intake of BHA = 0.57 (95% confidence interval (CI): 0.25-1.30] and BHT = 0.74 (95% CI: 0.38-1.43). In this study, no significant association with stomach cancer risk was found for usual intake of low levels of BHA and BHT.

Contact allergy to the monomers of p-tert-butylphenol-formaldehyde resin in the guinea pig.

In patients hypersensitive to p-tert-butylphenol-formaldehyde resin (PTBP-F-R), and butylphenol derivatives therein, it is for diagnostic, therapeutic and preventive reasons necessary to know the identity of the primary sensitizing substances, their sensitizing capacities as well as their cross-reaction patterns. The monomers in PTBP-F-R, 2-methylol p-tert-butylphenol (2-MPTBP) and 2,6-dimethylol p-tert-butylphenol (2,6-MPTBP), have been shown to be contact sensitizers in man. The aim of this study was to investigate the sensitizing capacities of the monomers and establish cross-reacting patterns in the guinea pig with the guinea pig maximization test. 2,6-MPTBP was shown to be a strong sensitizer while it was indicated that 2-MPTBP was a sensitizer. Animals sensitized to 2,6-MPTBP showed cross-reactions to 2-MPTBP and p-tert-butylcatechol. No cross-reactions were shown to p-tert-butylphenol, tert-butyl 4-hydroxyanisole (BHA) and 3,5-di-tert-butyl 4-hydroxytoluene (BHT).

Assessment of the environmental behaviour of antioxidants in folios. Comparative risk analysis for the use of folios in agriculture.

The objective of the reported study has been to assess and evaluate as comprehensively as possible the environmental impact of Octadecyl 3(3,5-di-tert-butyl-4-hydroxyphenyl) propionate (CAS no: 2082-79-3, Irganox 1076, Ciba Specialty Chemicals Inc., Additives), which is used as an antioxidant. The potential impact on the compartments soil, groundwater and surface water is to be considered. For comparative purposes, additionally, other chemical compounds being currently under environmental discussion are also taken into account. These comprise pesticides and phthalates which are ubiquitously distributed plasticizers as well as a complexing agent. Since the data basis for each of the compounds under consideration is different, a tiered approach comprising various methodologies of impact assessment has been chosen to achieve the best possible comprehensiveness. The tiers are: 1. Tier: hazard assessment using a scoring system 2. Tier: comparative risk assessment. When interpreting the results of each method, system boundaries as well as underlying assumptions were taken into consideration. Both methodologies showed, that-as compared to the reference substances-there is no relevant environmental and toxicological concern due to low environmental and human hazard from Octadecyl 3(3,5-di-tert-butyl-4-hydroxyphenyl) propionate.

Contact allergy to 2-hydroxy-5-tert-butyl benzylalcohol and 2,6-bis(hydroxymethyl)-4-tert-butylphenol, components of a phenolic resin used in marking pens.

2-hydroxy-5-tert-butyl benzylalcohol and 2,6-bis(hydroxymethyl)-4-tert-butylphenol were identified as contact allergens in a phenolic resin used as a tackifier in the ink of a marking pen, which, after being used directly on the skin, caused an acute contact dermatitis on the hand of a 13-year-old boy. The patient also reacted to 4-tert-butylphenol-formaldehyde resin (BPF resin) 1% pet. included in the European standard series.

Contact dermatitis from dielectric fluids in electrodischarge machining.

We report an outbreak of irritant contact dermatitis in the aerospace industry from electrodischarge machining (EDM). 20 workers doing EDM developed irritant contact dermatitis from the dielectric fluid used in EDM, a form of precision metal machining that is widely used in mould making and precision engineering. Dielectric fluid contains hydrocarbons that are aromatic, paraffinic or naphthenic and are skin irritants. Irritant contact dermatitis from dielectric fluid has not been reported previously. EDM will become more widespread and occupational dermatitis from dielectric fluid is likely to become more prevalent in the future. Our experience was that irritant contact dermatitis from dielectric fluid can be prevented by simple preventive measures such as personal hygiene and health education.

Sensitizing risk of butylated hydroxytoluene based on exposure and effect data.

A national database on chemical products (the Danish Product Register (PROBAS) was searched for products containing butylated hydroxytoluene (BHT). As of March 1990, 440 products containing BHT were registered. The content of BHT was below 50 ppm in 66% of these products. Paints/lacquers (1- and 2-component) and hardeners for 2-component paints, glues, fillers, etc. make up the main categories. No positive reactions were seen in 1336 consecutive eczema patients patch tested with BHT. From the widespread use of BHT, it was considered that BHT could be regarded as a safe antioxidant in the normally used concentrations. The possibilities, limitations, and demands of product registration as exposure estimates are discussed.