Disease relevance of Mequinol

• Twelve weeks later the mice were sacrificed and forestomach tumors were counted and confirmed histologically as papillomas. p-Methoxyphenol was the most effective inhibitor and was the only one which significantly reduced both the percentage of tumor-bearing animals and the number of forestomach tumors per animal [1].
• Groups of 20 rats were given an intragastric dose of 150 mg/kg body weight MNNG, and starting from 1 week later received diet supplemented with 0.8% catechol (CC), 1.0% 2-tert-butyl-4-methylphenol, 1.5% p-tert-butyl-phenol, 1.5% methylhydroquinone, 1.5% 4-methoxyphenol (4MP), or basal diet alone for 51 weeks [2].
• The drug p-hydroxyanisole (OHA) was found to inhibit the incorporation of 3H-thymidine in the Harding-Passey melanoma cells in culture [3].
• Other quinone derivatives, i.e., p-methoxyphenol, AA-861 and idebenone, failed to inhibit the toxicity and cell-surface adhesion of amylin aggregates [4].
• PMOP induced epithelial damage and regenerative hyperplasia of the pyloric region [5].

Psychiatry related information on Mequinol

• p-methoxyphenol: chemical basis of stench of a female butterfly. Defense mechanisms of arthropods, No. 91 [6].

High impact information on Mequinol

• These results clearly demonstrated that while antioxidants causing proliferation in forestomach epithelium can markedly enhance carcinogenesis in this tissue, others displaying the same or greater potential for generating a hyperplastic response, like 4MP, can exert an inhibitory effect [2].
• Identification by electron spin resonance of free radicals formed during the oxidation of 4-hydroxyanisole catalyzed by tyrosinase [7].
• Among the p-alkoxyphenols studied, p-propoxyphenol was the most effective inhibitor of mouse R2 (IC50, 0.7 microM) and p-methoxyphenol was the least effective (IC50, 11 microM); p-ethoxy- and p-allyloxyphenol were intermediate [8].
• Carcinogenicity of 4-methoxyphenol and 4-methylcatechol in F344 rats [9].
• A combination of 4-hydroxyanisole (4HA) and all-trans retinoic acid (TRA) was found to synergistically cause moderate to complete depigmentation of Yucatan swine skin [10].

Chemical compound and disease context of Mequinol

• In amelanotic melanoma tissue tyrosine radicals of the enzyme are also quenched by 4-hydroxyanisole in concentrations down to 50 microM [11].
• Chemoprevention of azoxymethane-induced colon cancer by ascorbylpalmitate, carbenoxolone, dimethylfumarate and p-methoxyphenol in male F344 rats [12].
• Solagé is a combination product composed of 2% mequinol (4-hydroxyanisole) and 0.01% tretinoin (all-trans-retinoic acid) in an ethanolic solution, which is being studied for its safety and efficacy as a topical treatment for disorders of skin hyperpigmentation [13].
• Cell division of the wild type strain Corynebacterium (formerly Brevibacterium) ammoniagenes ATCC 6872 which requires 1 microM Mn2+ for balanced growth was inhibited by addition of 20 mM hydroxyurea (HU) or 10 mM p-methoxyphenol (MP) to a Mn2+-supplemented fermentation medium at an appropriate time [14].

Biological context of Mequinol

• Oxygen consumption for complete oxidation of 200 nmol of 4HA was constant over a range of concentrations of tyrosinase of 33-330 units/ml of substrate [15].
• Studies on the kinetics of oxidation of 4-hydroxyanisole by tyrosinase [16].
• 4-Hydroxyanisole: human pharmacokinetics [17].
• It is concluded that there is no evidence that enzyme induction influences the clearance of 4-hydroxyanisole from the bloodstream in the short-term [17].
• Metabolic activation of 4-hydroxyanisole by isolated rat hepatocytes [18].

Anatomical context of Mequinol

• Cultured normal mammalian melanocytes exposed to a variety of antioxidants in the presence of millimolar concentrations of 4-hydroxyanisole exhibit dose-dependent modifications of cytotoxicity [19].
• Estimations on rat liver microsomes in the presence of tyrosinase and 4-hydroxyanisole showed increased peroxidation only at low substrate concentrations [19].
• To elucidate the mechanism of the hepatotoxicity of 4-hydroxyanisole (4-HA), its effect on the viability of mouse hepatocytes in suspension was investigated [20].
• These microsomes, along with 4-methoxyphenol microsomes, also showed a substantial reduction in DNA binding of benzo(a)pyrene (BaP) metabolites relative to metabolism [21].
• An experimental study using human melanoma (NEL-MI), rat hepatoma (Fu5-5), and human kidney (293-31) cell lines was undertaken in order to evaluate the antitumor activity of 4-hydroxyanisole (4-OHA) in vitro [22].

Associations of Mequinol with other chemical compounds

• The effect of thiol compounds on the monophenolase activity of tyrosinase was investigated using 4-hydroxyanisole as the substrate and dithiothreitol (DTT) as the model thiol compound [23].
• (5) Ability in vitro to discharge the activated oxygen complex of cytochrome P450 was: 2,6-di-t-butylphenol approximately 2-t-butylphenol greater than BHA greater t-butylhydroquinone greater than 4-methylmercaptophenol greater than 4-methoxyphenol [21].
• A tyrosinase inhibitor in use in Europe, 4-hydroxyanisole (Mequinol), and the retinoid tretinoin have been used singly as depigmenting agents [24].
• Three monomers, 2-hydroxyethyl methacrylate, methyl methacrylate, and 2-ethoxyethyl methacrylate, as well as two common inhibitors, hydroquinone and 4-methoxyphenol, were subjected to in vitro cytotoxicity assays as aqueous solutions at different concentrations [25].
• Evidence is presented that the first and major product of the oxidation of 4-hydroxyanisole (4HA) by tyrosinase is 4-methoxy ortho benzoquinone (4-MOB) [26].

Gene context of Mequinol

• In these cells DT-diaphorase activity could be induced by incubation of the cells with 4-hydroxyanisole [27].
• In order to clarify the role of tyrosinase (E.C. 1.14.18.1) in the cytotoxicity of 4-hydroxyanisole (4HA) in vivo, we have compared the therapeutic effects of 4HA on the B16 melanoma and Harding-Passey melanoma, which differ significantly in their tyrosinase content [28].
• Depigmentation therapy in vitiligo universalis with topical 4-methoxyphenol and the Q-switched ruby laser [29].
• We studied the response of mouse B16F10 and SK-MEL-28 and SK-MEL-1 human melanoma cell lines to treatment with 4-hydroxyanisole (4-HA), and attempted to relate the response to the dopa oxidase levels and the morphological characteristics of each cell line [30].

Analytical, diagnostic and therapeutic context of Mequinol

• Riley's classic 1970 experiment showing a specific cytotoxic effect of 4-hydroxyanisole (4-OHA) on tissue-cultured melanocytes of black guinea pig ear skin was repeated on normal human melanocytes, and the results were examined by electron microscopy [31].
• Measurement of 4-hydroxyanisole in serum by direct injection high-performance liquid chromatography [32].
• Column chromatography and SDS-PAGE separation showed labelling of the enzyme when incubated with 14C ring-labelled 4-hydroxyanisole [33].
• Patients were treated with topical mequinol 2%/tretinoin 0.01% and clinically evaluated at 4, 8, 12, 16, 20, and 24 weeks as well as 4 weeks following treatment cessation [34].
• In terms of the results obtained by cytogenetic analysis the reduction of genetic instability seems to remain constant from the first to the sixth passage in the cell cultures treated with p-methoxyphenol phosphate associated to benzo(a)pyrene [35].

References