Disease relevance of BUTYLATED HYDROXYANISOLE

• The incidence of epithelial hyperplasia of the forestomach increased with the increased BHA doses, to 100% incidence at the highest dose [1].
• Papillomas of the forestomach developed in 20 and 100% of the rats given diets containing 1 and 2% BHA, respectively [1].
• Differences in the incidences of squamous cell carcinoma between the controls and groups given BHA, BHA plus NaCl, and BHT plus NaCl were statistically significant [2].
• Effects of administration to mice of butylated hydroxyanisole by oral intubation on benzo[a]pyrene-induced pulmonary adenoma formation and metabolism of benzo[a]pyrene [3].
• Butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) exhibited antimutagenic activity in the Salmonella typhimurium reversion test [4].

Psychiatry related information on BUTYLATED HYDROXYANISOLE

• After hatching, swim-up, and the onset of vigorous feeding behavior (2 weeks pest swim-up), duplicate groups of 60 AFB1-treated and sham-treated fry were started on a test diet containing 0.6% (6000 ppm) BHA, and the other duplicate groups of treated and untreated fry were fed the control Oregon Test Diet (OTD) [5].
• Information gleaned from the BHA and EDB studies with multiple animal species facilitated regulatory decision-making regarding the potential toxicity/carcinogenicity of these compounds to man [6].
• In the maintenance of shelf-stability, nutritional and organoleptic properties of ground melon 'egusi'-Colocynthis citrullus L., vacuum-packaged samples were found to be better than unpackaged samples and samples treated with 0.2% butylated hydroxyanisole (BHA) and 0.02% BHA + 0.045% sodium metabisulphite [7].

High impact information on BUTYLATED HYDROXYANISOLE

• As in tumor necrosis factor (TNF)-induced necrosis, Fas treatment led to accumulation of reactive oxygen radicals, and Fas-mediated necrosis was inhibited by the oxygen radical scavenger butylated hydroxyanisole [8].
• Lowering the cooking temperatures or adding an antioxidant, such as butylated hydroxyanisole, before cooking decreased the amount of these volatile emissions [9].
• Iron and copper accelerated the rate of cell death, whereas antioxidants such as vitamin E and butylated hydroxyanisole inhibited the effect of GLA dose dependently [10].
• While inhibiting the development of hepatocellular lesions, especially in the group initiated with DENA, and while itself inducing extensive papillomatous forestomach hyperplasia, BHA administration did not exert a significant modifying influence on tumorigenesis in other organs [11].
• Comparison of lesions induced in the Syrian golden hamster by diethylnitrosamine, dimethylhydrazine, and dibutylnitrosamine: influence of subsequent butylated hydroxyanisole treatment [11].

Chemical compound and disease context of BUTYLATED HYDROXYANISOLE

• Rats were fed either a 2(3)-tert-butyl-4-hydroxyanisole (0.5% w/w)- or ethoxyquin (0.5% w/w)-containing diet with or without ciprofibrate (10 mg/kg of body weight) for 60 weeks [12].
• While non-hepatocarcinogens exerted no such effects, their influence being limited to inducing lesions in their own respective target organs such as urinary bladder cancers in the EHBN case and glandular stomach adenocarcinomas with MNNG, BHA demonstrated inhibition potential in both experiments [13].
• Inhibition of prostaglandin H synthase by ASA in cultures treated with TBHQ decreased the oxidation ratio significantly, confirming the significance of this enzyme system in the mechanism of toxicity of BHA [14].
• We have tested this hypothesis by examining the ability of butylated hydroxyanisole (BHA), ethoxyquin, and other antioxidants to prevent thyroiditis in Obese strain (OS) chickens, a strain that develops severe disease by 4 weeks of age [15].
• However, the incidence and multiplicity of papillomas in the group given BHA + DHEA + RNs were again elevated [16].

Biological context of BUTYLATED HYDROXYANISOLE

• These results suggested that BHA and BHT may inhibit the metabolic activation processes and demonstrated that the S. typhimurium reversion test may be used to identify inhibitors of the neoplastic process [4].
• Activation of these proteases and apoptosis were suppressed by the cytokine interleukin 6 or by a combination of the cytokine interferon gamma and the antioxidant butylated hydroxyanisole, and activation of poly(ADP-ribose) polymerase and apoptosis were suppressed by some protease inhibitors [17].
• While hyperplasia in the prefundic region most likely dominates the carcinogenicity of BHA, a mechanism combining marginal genotoxicity with strong promotion by increased cell proliferation appears to be involved in the tumorigenic action of SO [18].
• Cell kinetics of reversible and persistent forestomach lesions induced by the genotoxic agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and/or the nongenotoxic antioxidant butylated hydroxyanisole (BHA) was investigated [19].
• The dose-response curves for protein binding of BP metabolites in lung and liver from BHA-treated animals were essentially parallel to those in control animals and thus, the inhibition of protein binding by BHA treatment had no dose dependency in these organs [20].

Anatomical context of BUTYLATED HYDROXYANISOLE

• The data showed that BHA feeding resulted in altered properties of liver microsomes, including a decrease in BP metabolite binding to DNA [21].
• Incubation of BP with liver microsomes from mice that received BHA 2,4, or 8 hours before being killed resulted in less binding of BP metabolites to added DNA than occurred with control microsomes [3].
• Whereas the 2 antioxidants BHA and TC inhibited the incidence of both liver and pancreatic lesions, CA, itself giving rise to considerable numbers of enzyme-altered foci, enhanced carcinogenesis in the liver while inhibiting carcinogenesis in the pancreas [22].
• However, BHA has multiple biologic actions so that its inhibitory effect on MAM acetate-induced neoplasia of the large intestine may entail some other mechanism [23].
• Incubation of BP and calf thymus DNA with liver microsomes from BHA-fed mice showed about half the binding of BP metabolites to DNA as compared to that of controls [21].

Associations of BUTYLATED HYDROXYANISOLE with other chemical compounds

• BHT and BHA treatments reduced the number of acidophilic foci per pancreas by 32 and 48%, respectively, but were without effect on focal size [24].
• In the present work, BHA, when added to the diet, inhibited the carcinogenic action of methylazoxymethanol (MAM) acetate on the large intestine of female CF1 mice [23].
• Superoxide dismutase (100 micrograms/ml), and the general free radical scavengers butylated hydroxytoluene and butylated hydroxyanisole (50 microM), inhibited Fe- and Cu-mediated modification of LDL by monkey smooth muscle cells, while catalase (100 micrograms/ml) and mannitol (25 mM) had no effect [25].
• Histologic and autoradiographic studies on the forestomach of hamsters treated with 2-tert-butylated hydroxyanisole, 3-tert-butylated hydroxyanisole, crude butylated hydroxyanisole, or butylated hydroxytoluene [26].
• The increases in cytosolic DT-diaphorase activities in organs of mice fed 0.5% bisethylxanthogen were similar in magnitude to those observed previously in response to 0.75% butylated hydroxyanisole [27].

Gene context of BUTYLATED HYDROXYANISOLE

• Activation of ERK2 by BHA was rapid and transient, whereas the JNK1 activation was relatively delayed and persistent [28].
• Amongst class Pi transferase subunits, the constitutive hepatic level of mRNA for Gstp1 and Gstp2 was not substantially affected in the KO mice, but their induction by BHA was dependent on Nrf2; this was more obvious in female mutant mice than in male mice [29].
• We next examined the phosphorylation of the MAPKs, and found that BHA significantly increased the phosphorylation levels of ERK1/2 and JNK1/2 [30].
• Semi-quantitative RT-PCR study and microarray analysis revealed that HO-1 and NQO1 were transcriptionally activated in primary-cultured rat hepatocytes and a substantial transcriptional activation, including HO-1 occurred in primary-cultured human hepatocytes after BHA treatment [31].
• Non-significant modulation of catalase activity by BHA was also noted [32].

Analytical, diagnostic and therapeutic context of BUTYLATED HYDROXYANISOLE

• Neoplastic effects of oral administration of (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene and their inhibition by butylated hydroxyanisole [33].
• Squamous cell carcinomas of the forestomach were seen in 2 of 18 effective rats (11.1%) in the control groups, and the incidences in the groups receiving the subsequent treatment were 45.0% with BHA, 15.8% with BHT, 30% with NaCl, 70% with BHA plus NaCl, and 52.9% with BHT plus NaCl [2].
• High-pressure liquid chromatography studies of the BP metabolite pattern produced by the incubation of BP with liver microsomes from mice given BHA by oral intubation showed a decrease in formation of BP-4,5-oxide and 9-hydroxybenzo[a]pyrene [3].
• To determine the functional role of NF-kappa B in early thymocyte development, we have exposed fetal thymus organ cultures to inhibitors of NF-kappa B activation, namely the antioxidants N-acetyl-L-cysteine and butylated hydroxyanisole [34].
• After treatment of quiescent human hepatoma HepG2 cells with butylated hydroxytoluene, butylated hydroxyanisole, or other phenolic antoxidants, the levels of c-fos and c-jun mRNAs are substantially increased [35].

References