Melatonin protects against gastric ulceration and increases the efficacy of ranitidine and omeprazole in reducing gastric damage

Bandyopadhyay, Debashis; Bandyopadhyay, Arun; Das, Priya; Reíter, Russel J.

doi:10.1034/j.1600-079x.2002.01107.x

Cited by 49 publications

(47 citation statements)

References 56 publications

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“…Functional connections between vitamin D and melatonin have been pointed out (72,73) and are considered relevant for harmonious regulations in a natural environment. Evidence exists in the literature for melatonin actions on the digestive system as well, such as protective effects against gastric ulceration (74,75) and periodontal inflammatory disease (76), uptake of melatonin-related compound in submandibular gland (77) and secretion of nerve growth factor (78). Identification of melatonin targets is still lacking but would be indispensable for clarification and assessment of functional relationships between these hormonal regulators and solar zeitgebers (72).…”

Section: Discussionmentioning

confidence: 99%

Vitamin D and the digestive system

Stumpf

2008

Eur. J. Drug Metabol. Pharmacokinet.

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Target tissues of in vivo receptor binding and deposition of 1,25(OH)2 vitamin D3 and its oxygen analog OCT are reviewed in rats, mice, hamsters and zebra finch, identified with high-resolution microscopic autoradiography. Throughout the digestive system numerous sites with nuclear receptor binding of 3H-1,25(OH)2 vitamin D3 and 3H-OCT exist: in the oral region, epithelial cells of the oral cavity, tongue and gingiva, teeth odontoblast and ameloblast precursor pulp and stratum intermedium cells; in the parotid, submandibular and sublingual salivary glands, epithelial cells of striated ducts and granular convoluted tubules, intercalated ducts and acinar cells, as well as myoepithelial cells; in the stomach, neck mucous cells of gastric glands, endocrine cells of the antrum, and muscle cells of the pyloric sphincter; in the small and large intestine, absorptive and crypt epithelial cells; in the pancreas, predominantly islet B-cells. Perisinusoidal stellate (Ito) cells in the liver concentrate and retain variable amounts of radiolabeled compound in regions of their cytoplasm after administration of 3H-I,25(OH)2 vitamin D3 and 3H-25(OH) vitamin D3, probably sites of specific storage, similar to vitamin A. Submucosa in stomach and intestine also retain variable amounts of radiolabel, however unspecific with all compounds studied. In pilot studies with 3H-25(OH)2 vitamin D3 and 3H-24,25(OH)2 vitamin D3, no nuclear concentration was detectable. The reviewed data for vitamin D and its oxygen analogue OCT indicate genomic effects on multiple target tissues of the digestive system that involve cell proliferation and differentiation, endo- and exocrine secretion, digestion and absorption for maintaining optimal functions, with potentials for health prophylaxis and therapies.

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Section: Discussionmentioning

confidence: 99%

Vitamin D and the digestive system

Stumpf

2008

Eur. J. Drug Metabol. Pharmacokinet.

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“…Several studies have compared melatonin' s e cacy in protecting against stress-induced gastric ulceration with widely used anti-ulcer medication such as ranitidine and omeprazole (Bandyopadhyay et al 2000(Bandyopadhyay et al , 2001(Bandyopadhyay et al , 2002. Ranitidine blocks histamine-stimulated acid secretion in the stomach while omeprazole, a substituted benzimidazole, completely interrupts acid secretion.…”

Section: Ranitidine and Omeprazolementioning

confidence: 99%

Melatonin: reducing the toxicity and increasing the efficacy of drugs

Reíter¹,

Tan²,

Sainz³

et al. 2002

Journal of Pharmacy and Pharmacology

378

300

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Melatonin (N-acetyl-5-methoxytryptamine) is a molecule with a very wide phylogenetic distribution from plants to man. In vertebrates, melatonin was initially thought to be exclusively of pineal origin ; recent studies have shown, however, that melatonin synthesis may occur in a variety of cells and organs. The concentration of melatonin within body uids and subcellular compartments varies widely, with blood levels of the indole being lower than those at many other sites. Thus, when de ning what constitutes a physiological level of melatonin, it must be de ned relative to a speci c compartment. Melatonin has been shown to have a variety of functions, and research in the last decade has proven the indole to be both a direct free radical scavenger and indirect antioxidant. Because of these actions, and possibly others that remain to be de ned, melatonin has been shown to reduce the toxicity and increase the ef cacy of a large number of drugs whose side effects are well documented. Herein, we summarize the bene cial effects of melatonin when combined with the following drugs: doxorubicin, cisplatin, epirubicin, cytarabine, bleomycin, gentamicin, ciclosporin, indometacin, acetylsalicylic acid, ranitidine, omeprazole, isoniazid, iron and erythropoietin, phenobarbital, carbamazepine, haloperidol, caposide-50, morphine, cyclophosphamide and L-cysteine. While the majority of these studies were conducted using animals, a number of the investigations also used man. Considering the low toxicity of melatonin and its ability to reduce the side effects and increase the ef cacy of these drugs, its use as a combination therapy with these agents seems important and worthy of pursuit.

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“…In the stomach, melatonin was found to inhibit acid secretion [6,7], and it induces duodenal HCO 3 -secretion in response to gastric acid [8]. Studies in animals showed that melatonin stimulates pancreatic enzyme secretion and improves the outcome of experimental pancreatitis [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Melatonin Modulates Acid/Base Transport in Human Pancreatic Carcinoma Cells

Aust

Brucker²,

Graf³

et al. 2006

Cell Physiol Biochem

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Melatonin was found to improve pancreatic organ function in diseased animals. To study whether pancreatic bicarbonate secretion is stimulated by melatonin, investigations were done in two human ductal pancreatic adenocarcinoma cell lines MIA PaCa-2 (MIA) and PANC-1 (PANC). Using the fluorescence pH-sensor BCECF-AM, we monitored melatonin effects on basal intracellular pH (pH_i), and on pH_i recovery after intracellular alkalinization produced by the removal of extracellular HCO₃ ^-/CO₂. Exposure to 1µM melatonin for 24hrs and presence of the indoleamine during the experiment increases the basal pH_i. Moreover, pHi recovery and HCO₃ ^- secretion are facilitated after the alkaline load. These findings are in line with the observed increase in mRNA expression of the Na⁺/HCO₃ ^--cotransporter SLC4A4b for the uptake and the Cl^-/HCO₃ ^--exchanger SLC26A6 for the secretion of HCO₃ ^-. The reduction in Na⁺/H⁺- exchanger SLC9A1 mRNA would favor pH_i recovery after alkalinization, but it does not explain the initial increase in pHi. This controversial effect and the requirement for continuous presence of melatonin throughout the experiment suggest that nontranscriptional signalling may contribute to the effects of melatonin on acid/base movements. In summary, we show a stimulatory effect of melatonin on bicarbonate secretion in the pancreatic cancer cell lines which may help to prevent duodenal damage.

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Melatonin protects against gastric ulceration and increases the efficacy of ranitidine and omeprazole in reducing gastric damage

Cited by 49 publications

References 56 publications

Vitamin D and the digestive system

Vitamin D and the digestive system

Melatonin: reducing the toxicity and increasing the efficacy of drugs

Melatonin Modulates Acid/Base Transport in Human Pancreatic Carcinoma Cells

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