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Archives Internationales de... Oct 1984Chronic treatment with trithio-p-methoxyphenylpropene (anethole trithione; ANTT) increased the salivary secretion from the rat submaxillary gland induced by electrical...
Chronic treatment with trithio-p-methoxyphenylpropene (anethole trithione; ANTT) increased the salivary secretion from the rat submaxillary gland induced by electrical stimulation of the parasympathetic nerve and by injection of pilocarpine. In parallel with the enhancement of the salivary secretion, the number of the muscarinic acetylcholine receptors was significantly increased. The increased number of receptors may be involved in the enhancement of the salivary secretion by ANTT treatment.
Topics: Anethole Trithione; Animals; Anisoles; Male; Quinuclidinyl Benzilate; Rats; Rats, Inbred Strains; Receptors, Muscarinic; Salivation; Submandibular Gland; Tritium
PubMed: 6508432
DOI: No ID Found -
Nature Communications Aug 2022Inefficient tumour treatment approaches often cause fatal tumour metastases. Here, we report a biomimetic multifunctional nanoplatform explicitly engineered with a...
Inefficient tumour treatment approaches often cause fatal tumour metastases. Here, we report a biomimetic multifunctional nanoplatform explicitly engineered with a Co-based metal organic framework polydopamine heterostructure (MOF-PDA), anethole trithione (ADT), and a macrophage membrane. Co-MOF degradation in the tumour microenvironment releases Co, which results in the downregulation of HSP90 expression and the inhibition of cellular heat resistance, thereby improving the photothermal therapy effect of PDA. HS secretion after the enzymatic hydrolysis of ADT leads to high-concentration gas therapy. Moreover, ADT changes the balance between nicotinamide adenine dinucleotide/flavin adenine dinucleotide (NADH/FAD) during tumour glycolysis. ATP synthesis is limited by NADH consumption, which triggers a certain degree of tumour growth inhibition and results in starvation therapy. Potentiated 2D/3D autofluorescence imaging of NADH/FAD is also achieved in liquid nitrogen and employed to efficiently monitor tumour therapy. The developed biomimetic nanoplatform provides an approach to treat orthotopic tumours and inhibit metastasis.
Topics: Biomimetic Materials; Biomimetics; Energy Metabolism; Flavin-Adenine Dinucleotide; Humans; Hypothermia; NAD; Neoplasms; Tumor Microenvironment
PubMed: 35931744
DOI: 10.1038/s41467-022-32349-2 -
Oxidative Medicine and Cellular... 2020Anethole dithiolethione (ADT) is a marketed drug to treat xerostomia. Its mechanism of action is still unknown, but several preclinical studies indicate that it is able...
AIMS
Anethole dithiolethione (ADT) is a marketed drug to treat xerostomia. Its mechanism of action is still unknown, but several preclinical studies indicate that it is able to increase intracellular glutathione (GSH) and protect against oxidative stress. Here, we investigated the molecular mechanisms behind these effects.
RESULTS
Oral treatment of rats confirmed the GSH enhancing properties of ADT; among the different organs examined in this study, only the kidney showed a significant GSH increase that was already observed at low-dose treatments. The increase in GSH correlated with a decrease in -glutamyltranspeptidase (-GT) activity of the different tissues. and experiments with tubular renal cells and isolated perfused rat kidney showed that the cellular uptake of intact GSH was correlated with the extracellular concentrations of GSH.
CONCLUSION
s. The prominent pharmacological effect of ADT was a marked increase of GSH concentration in the kidney and a decrease of some systemic and renal biomarkers of oxidative stress. In particular, by inhibition of -GT activity, it decreased the production cysteinylglycine, a thiol that has prooxidant effects as the consequence of its autooxidation. The activity of ADT as GSH enhancer in both the circulation and the kidney was long-lasting. All these characteristics make ADT a promising drug to protect the kidney, and in particular proximal tubule cells, from xenobiotic-induced damage.
Topics: Anethole Trithione; Animals; Cell Line; Cysteine; Dipeptides; Disulfides; Glutathione; Humans; Kidney; Kidney Tubules, Proximal; Male; Malondialdehyde; Oxidative Stress; Rats; Rats, Sprague-Dawley; gamma-Glutamyltransferase
PubMed: 33062138
DOI: 10.1155/2020/3562972 -
Drug Metabolism and Disposition: the... Oct 2018A study of the metabolism of anethole dithiolethione (ADT, 5-(p-methoxyphenyl)-3-1,2-dithiole-3-thione) by rat and human liver microsomes showed the formation of the...
Metabolism of Anethole Dithiolethione by Rat and Human Liver Microsomes: Formation of Various Products Deriving from Its -Demethylation and -Oxidation. Involvement of Cytochromes P450 and Flavin Monooxygenases in These Pathways.
A study of the metabolism of anethole dithiolethione (ADT, 5-(p-methoxyphenyl)-3-1,2-dithiole-3-thione) by rat and human liver microsomes showed the formation of the corresponding -oxide and the -oxide of desmethyl-ADT (dmADT, 5-(p-hydroxyphenyl)-3-1,2-dithiole-3-thione), and of p-methoxy-acetophenone (pMA) and p-hydroxy-acetophenone (pHA), in addition to the previously described metabolites, dmADT, anethole dithiolone (ADO, 5-(p-methoxyphenyl)-3-1,2-dithiole-3-one) and its demethylated derivative dmADO [5-(p-hydroxyphenyl)-3-1,2-dithiole-3-one]. The microsomal metabolism of ADO under identical conditions led to dmADO and to pMA and pHA. The metabolites of ADT derive from two competing oxidative pathways: an -demethylation catalyzed by cytochromes P450 and an -oxidation mainly catalyzed by flavin-dependent monooxygenases (FMO) and, to a minor extent, by CYP enzymes. The most active human CYP enzymes for ADT demethylation appeared to be CYP1A1, 1A2, 1B1, 2C9, 2C19, and 2E1. ADT -oxidation is catalyzed by FMO 1 and 3, and to a minor extent by CYP enzymes such as CYP3A4.
Topics: Anethole Trithione; Animals; Cytochrome P-450 Enzyme System; Demethylation; FMN Reductase; Humans; Male; Metabolomics; Microsomes, Liver; Mixed Function Oxygenases; Oxidation-Reduction; Rats; Rats, Sprague-Dawley
PubMed: 30018103
DOI: 10.1124/dmd.118.082545 -
The Journal of Pharmacy and Pharmacology Apr 1989The effect of chronic treatment with anethole trithione (ANTT) on the phosphatidylinositol (PI) turnover and cyclic (c)AMP and cGMP accumulation in rat submaxillary...
The effect of chronic treatment with anethole trithione (ANTT) on the phosphatidylinositol (PI) turnover and cyclic (c)AMP and cGMP accumulation in rat submaxillary glands (SMG) has been compared with the effect of chronic treatment with atropine and a cholinesterase inhibitor, diisopropylfluorophosphate (dyflos, DFP). Experiments were performed 24, 48 and 24 h after the last dose of ANTT, atropine and dyflos, respectively. ANTT and atropine enhanced carbachol-stimulated [32P] incorporation into phosphatidic acid in the SMG slices, while dyflos showed no effect. Pilocarpine-stimulated in-vivo incorporation of [3H]myoinositol into inositol phosphates was significantly enhanced by ANTT, but not by atropine or by dyflos. Phospholipase C-dependent hydrolysis of phosphatidylinositol 4,5-bisphosphate was significantly enhanced by ANTT and atropine, but not by dyflos. Pilocarpine-stimulated in-vivo accumulation of cAMP and cGMP was enhanced by ANTT and atropine, but dyflos reduced cAMP accumulation without affecting cGMP accumulation. The enhancement of PI turnover and cyclic nucleotide accumulation seems to contribute to the development of supersensitivity of the salivary gland caused by chronic treatment with ANTT and atropine, while reduction of cAMP accumulation may be responsible for the subsensitivity caused by dyflos.
Topics: Anethole Trithione; Animals; Anisoles; Atropine; Carbachol; Cyclic AMP; Cyclic GMP; In Vitro Techniques; Inositol; Isoflurophate; Male; Phosphatidylinositols; Pilocarpine; Rats; Rats, Inbred Strains; Submandibular Gland; Type C Phospholipases
PubMed: 2568464
DOI: 10.1111/j.2042-7158.1989.tb06444.x -
Oral Surgery, Oral Medicine, and Oral... Feb 1993Sialagogues constitute an important component in the management of salivary gland dysfunction. Of the pharmacologic agents available, pilocarpine has been used... (Review)
Review
Sialagogues constitute an important component in the management of salivary gland dysfunction. Of the pharmacologic agents available, pilocarpine has been used extensively over the last century. Many clinical trials have documented the efficacy of this alkaloid, with doses that range from 1 to 15 mg normally taken four times a day. There is considerable individual variation in response although it is usually possible, in the presence of sufficient responsive exocrine tissue, to establish a therapeutic regimen that promotes increased salivation without significant side effects.
Topics: Anethole Trithione; Bethanechol; Bethanechol Compounds; Humans; Parasympathomimetics; Pilocarpine; Pyridostigmine Bromide; Salivary Gland Diseases; Xerostomia
PubMed: 8093976
DOI: 10.1016/0030-4220(93)90092-i -
Archives Internationales de... 1988Effect on salivary secretion of a single dose and of chronic treatment with trithio-p-methoxyphenylpropene (anethole trithione; ANTT) was investigated in mice, rats and... (Comparative Study)
Comparative Study
Effect on salivary secretion of a single dose and of chronic treatment with trithio-p-methoxyphenylpropene (anethole trithione; ANTT) was investigated in mice, rats and rabbits in relation to changes in function of the autonomic nervous system. Chronic treatment with ANTT enhanced salivary secretion induced by pilocarpine or electrical stimulation of the parasympathetic nerve, but had no effect on salivary secretion induced by isoproterenol or phenylephrine. A single dose of ANTT had no effect on salivary secretion. Chronic treatment with ANTT prevented the inhibition of parotid salivary secretion caused by atropine in rabbits. Choline acetyltransferase and acetylcholinesterase activities in rat submaxillary glands were not affected by chronic treatment with ANTT. These results suggest that chronic treatment with ANTT may enhance salivary secretion by stimulating the postjunctional secretory process involved in the parasympathetic nervous system.
Topics: Anethole Trithione; Animals; Anisoles; Choline O-Acetyltransferase; Electrolytes; Mice; Mice, Inbred Strains; Pilocarpine; Rabbits; Rats; Rats, Inbred Strains; Saliva; Species Specificity; Stimulation, Chemical; Submandibular Gland
PubMed: 3233051
DOI: No ID Found -
Pathologie-biologie Jul 2004Tendinopathy and tendon rupture are the adverse effects observed with fluoroquinolone antibiotics in old patients. The aim of this study was to investigate the effect of...
Tendinopathy and tendon rupture are the adverse effects observed with fluoroquinolone antibiotics in old patients. The aim of this study was to investigate the effect of anethole dithiolethione (5-[p-methoxyphenyl]3H-1,2-dithiole-3-thione) on the oxidative stress induced by three fluoroquinolones (pefloxacin, ofloxacin, ciprofloxacin) incubated with rabbit tenocyte cell line. Anethole dithiolethione is a well known antioxidant and glutathione inducer. Anethole dithiolethione is widely used in human therapy for its choleretic, sialogogic properties and recently proposed as cytoprotective agent in lung precancerous lesions prevention in smokers. In this purpose, protection against oxidative stress induced by fluoroquinolones has been assessed using cytofluorimetric probes to quantify cytotoxicity and reactive oxygen species production. Fluorescence signal was quantified in 96-well microplates, using cold light cytofluorometer. Significant reactive oxygen species production was detected after 45 minutes for all fluoroquinolones tested. Anethole dithiolethione has been evaluated on this parameter. Anethole dithiolethione significantly (*: P<0.05) reduces and normalizes reactive oxygen species induced by fluoroquinolones. So, anethole dithiolethione (Sulfarlem), well known for its antioxidant and glutathione inducing properties, good tissue diffusion and good tolerance in humans, could be beneficially associated to fluoroquinolones, and be proposed as a therapeutic adjuvant to prevent oxidative stress and tendinous adverse effects induced by xenobiotics and more precisely by fluoroquinolones.
Topics: Anethole Trithione; Animals; Anticarcinogenic Agents; Cell Line; Cell Survival; Cells, Cultured; Humans; Lung Neoplasms; Oxidative Stress; Precancerous Conditions; Rabbits; Reactive Oxygen Species; Tendons
PubMed: 15261372
DOI: 10.1016/j.patbio.2003.11.001 -
Journal of Dental Research Feb 1987Salivary gland hypofunction occurs most often as a consequence of numerous drug therapies, anti-neoplastic treatments, or systemic disease. There are no universally...
Salivary gland hypofunction occurs most often as a consequence of numerous drug therapies, anti-neoplastic treatments, or systemic disease. There are no universally accepted means of treating gland dysfunction and the resultant subjective xerostomia. A few studies have suggested that treatment of underlying inflammatory connective tissue disease will improve salivary performance in Sjögren's syndrome. Most of these reports, however, have either been limited to a small number of patients or have failed to include objective measures of salivary gland output. A larger body of literature deals with attempts using many different sialogogues to stimulate salivary function in a variety of conditions. Again, many studies have failed to document salivary improvement objectively. Recently, interest has focused on three drugs: bromhexine, anethole-trithione, and pilocarpine hydrochloride. Studies with these agents are reviewed, and current clinical investigations with pilocarpine are presented in detail.
Topics: Anethole Trithione; Bromhexine; Humans; Pilocarpine; Salivary Gland Diseases; Salivary Glands; Xerostomia
PubMed: 3476633
DOI: 10.1177/00220345870660s214 -
Advances in Experimental Medicine and... 1997
Review
Topics: Allyl Compounds; Anethole Trithione; Animals; Anti-Inflammatory Agents, Non-Steroidal; Anticarcinogenic Agents; Arachidonic Acids; Aspirin; Colon; Colonic Neoplasms; Dinoprostone; Disulfides; Eflornithine; Food, Fortified; Ibuprofen; Intestinal Mucosa; Ornithine Decarboxylase; Ornithine Decarboxylase Inhibitors; Piroxicam; Pyrazines; Thiones; Thiophenes
PubMed: 9547649
DOI: No ID Found