Disease relevance of 3-METHYLINDOLE

• Putative mechanisms of toxicity of 3-methylindole: from free radical to pneumotoxicosis [1].
• Ruminal administration of 3-methylindole in goats severe pulmonary edema and respiratory distress [2].
• The results suggest that 3-methylindole in cigarette smoke may play an important role in the pathogenesis of small airway disease and emphysema, and that patients with severe liver diseases or portocaval shunt may be predisposed to diffuse alveolar damage by 3-methylindole produced in the intestinal tract [2].
• Transmission electron microscopy was used to characterize early pulmonary lesions in goats after a 2-hour intravenous infusion of 0.04 g 3-methylindole (3MI) per kilogram body weight [3].
• The morphogenesis of pulmonary lesions and associated edema induced by the pulmonary toxicant 3-methylindole (3-MI) was studied by combined light and transmission electron microscopy [4].

High impact information on 3-METHYLINDOLE

• Ultrastructural changes in intraacinar pulmonary veins. Relationship to 3-methylindole-induced acute pulmonary edema and pulmonary arterial changes in cattle [5].
• In 3-methylindole (3MI)-treated cattle electron-microscopic examination of intrapulmonary arteries showed changes of an arteritis which could be related to pulmonary hypertension [5].
• Pathologic changes in 3-methylindole-induced equine bronchiolitis [6].
• The present study shows that intravenous infusion of 3-methylindole (3MI) induced acute pulmonary edema in goats [7].
• 3-Methylindole may also induce proliferation of smooth endoplasmic reticulum in the remaining membranous pneumocytes and nonciliated columnar cells, indicating that these two cell types are involved in the xenobiotic function of the lung [2].

Chemical compound and disease context of 3-METHYLINDOLE

• Comparison of the fluorescence spectra and the effect of temperature on the quantum yields of fluorescence of Azurin (from Pseudomonas fluorescens ATCC-13525-2) and 3-methylindole (in methylcyclohexane solution) provides substantive evidence that the tryptophan residue in azurin is completely inaccessible to solvent molecules [8].
• The present experiment was designed to determine the effect of tissue concentrations of glutathione (GSH) and GSH-S-transferase activity on 3-methylindole (3MI)-induced pulmonary toxicity in vivo [9].
• An assay to measure the rate of enzymatic formation of 3-methylindole (3MI) from indoleacetic acid (IAA) in Lactobacillus sp. strain 11201 was developed [10].
• Rapid infusion of 3-methylindole (3-MI) dissolved in 10% Cremophor EL in water was immediately followed by pulmonary arterial hypertension, systemic arterial hypotension, decreased minute volume and periods of apnoea in goats [11].
• Available evidence supports the view that acute bovine pulmonary edema and emphysema (ABPE) is related to ruminal production of 3-methylindole (3MI) from L-tryptophan (TRP) [12].

Biological context of 3-METHYLINDOLE

• The results presented here describe the metabolic activation of zafirlukast via a similar mechanism to that described for 3-methylindole [13].
• For rats on the deficient diet, 3-methylindole suppressed lipid peroxidation by 50% of control [14].
• The mechanism of pneumotoxicity of 3-methylindole has been postulated to occur via protein alkylation or lipid peroxidation [15].
• Both compounds produced the same lesion at the LD50 dose, bronchiolar damage and mild alveolar edema, indicating that deuteration of 3-methylindole did not change the pathologic process [16].
• 3-Methylindole (3 MI) is a selective pulmonary toxicant, and cytochrome P450 (P450) bioactivation of 3 MI, through hydroxylation, epoxidation, or dehydrogenation pathways, is a prerequisite for toxicity [17].

Anatomical context of 3-METHYLINDOLE

• Ultrastructural pathology of intrapulmonary arteries in 3-methylindole-induced pneumotoxicity in cattle: II. Glycogen accumulation in the smooth muscle cells and intimal changes [18].
• Metabolism and bioactivation of 3-methylindole by human liver microsomes [19].
• On a triple quadrupole electrospray mass spectrometer, the neutral loss of the sugar, [M + H - 116](+), was utilized for selected reaction monitoring of the calf thymus DNA adducts, formed by incubations of 3-methylindole with various microsomes (rat liver, goat lung, and human liver) [20].
• Rat hepatocytes incubated with 3-methylindole produced the same three adducts, in approximately the same proportions, while no adducts were detected in untreated hepatocytes [20].
• Our report describes the effects of 3-methylindole on specific tryptophan binding to hepatic nuclear envelope receptor and discusses the possible implications thereof [21].

Associations of 3-METHYLINDOLE with other chemical compounds

• Addition of any one of many indolic or indole-related compounds, and particularly of 3-methylindole, does not inhibit in vitro binding of [3H]tryptophan to hepatic nuclear envelopes [21].
• 3-Methylindole was incubated with NADPH and goat lung or human liver microsomal proteins, and the proteins were hydrolyzed [22].
• Covalent binding of 3-[14C]methylindole (3[14C]MI) in crude microsomal preparations of goat lung, liver, and kidney was measured to determine if a reactive intermediate was formed during the in vitro metabolism of 3-methylindole (3MI) [23].
• Zinc suppression of free radicals induced in cultures of rat hepatocytes by iron, t-butyl hydroperoxide, and 3-methylindole [24].
• Thiols were added to incubations of goat lung microsomes with 3-methylindole and deuterated analogues of 3-methylindole to trap the imine intermediate as its thioether conjugates [25].

Gene context of 3-METHYLINDOLE

• In conclusion, CYP2E1 activity levels are more important than CYP2A activity levels for the metabolism of 3-methylindole in isolated pig hepatocytes [26].
• Human CYP2F1 bioactivates 3-methylindole (3MI), while mouse CYP2F2 bioactivates naphthalene [27].
• The toxicity of 3-methylindole (3 MI), a selective pneumotoxin, is dependent upon cytochrome P450-mediated bioactivation 3 [28].
• 3-Methylindole is a selective pneumotoxin that is oxidized by cytochrome P-450 enzymes to a reactive intermediate [22].
• The existence of a cytochrome P450-dependent 2,3-epoxide of the potent pneumotoxin 3-methylindole was indirectly confirmed using stable isotope techniques and mass spectrometry [29].

Analytical, diagnostic and therapeutic context of 3-METHYLINDOLE

• Spin-trapping of free radicals formed during in vitro and in vivo metabolism of 3-methylindole [30].
• 1 Rapid intravenous injection of 3-methylindole (3-MI) was shown to induce an anaphylactoid-like reaction in calves [31].
• 3-Methylindole-induced splenotoxicity: functional analysis of immune parameters and lymphocyte phenotyping by flow cytometry [32].
• Rat liver microsomes were trapped by an ultrafiltration membrane in a stirred flow-through chamber, and substrates for microsomal cytochrome P450 including hydroxychavicol, 3-methylindole, cyproheptadine and 2-tert-butyl-4,6-dimethylphenol were flow-injected individually through the chamber along with the cofactors, NADPH and glutathione [33].
• These cells are often observed to undergo progressive vesiculation, vacuolization and desquamation during 3-methylindole (3MI)-induced acute pulmonary edema after oral administration in goats and cattle [34].

References