Effect of melatonin and misoprostol on bacterial translocation in portal hypertensive rats

Topuz, Ömer; Ilhan, Yavuz Selim; Doğru, Osman; Aygen, Erhan; Sözen, Selim

doi:10.1111/j.1440-1746.2011.06875.x

Cited by 7 publications

(4 citation statements)

References 24 publications

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“…The cytoprotective effect following separate administration of misoprostol and melatonin reported by others, and verified by us, encouraged us to evaluate their combined local effect [50]. This resulted in a complete abolishment of the SDS-induced increase in CL Cr-EDTA .…”

Section: Discussionsupporting

confidence: 55%

Prevention of Rat Intestinal Injury with a Drug Combination of Melatonin and Misoprostol

Dahlgren

Cano-Cebrián

Hellström

et al. 2020

IJMS

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A healthy intestinal barrier prevents uptake of allergens and toxins, whereas intestinal permeability increases following chemotherapy and in many gastrointestinal and systemic diseases and disorders. Currently, there are no approved drugs that target and repair the intestinal epithelial barrier while there is a medical need for such treatment in gastrointestinal and related conditions. The objective of this single-pass intestinal perfusion study in rats was to investigate the preventive cytoprotective effect of three mucosal protective drugs—melatonin, misoprostol, and teduglutide—with different mechanisms of action on an acute jejunal injury induced by exposing the intestine for 15 min to the anionic surfactant, sodium dodecyl sulfate (SDS). The effect was evaluated by monitoring intestinal clearance of 51Cr-labeled ethylenediaminetetraacetate and intestinal histology before, during, and after luminal exposure to SDS. Our results showed that separate pharmacological pretreatments with luminal misoprostol and melatonin reduced acute SDS-induced intestinal injury by 47% and 58%, respectively, while their use in combination abolished this injury. This data supports further development of drug combinations for oral treatments of conditions and disorders related to a dysregulated or compromised mucosal epithelial barrier.

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Section: Discussionsupporting

confidence: 55%

Prevention of Rat Intestinal Injury with a Drug Combination of Melatonin and Misoprostol

Dahlgren

Cano-Cebrián

Hellström

et al. 2020

IJMS

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“…Furthermore, tuberculosis chemotherapy using isoniazid is improved by melatonin (Wiid et al , ). Melatonin administration also reduced the incidence of bacterial translocation in intestinal ischaemia/reperfusion (Sozen et al , ), major liver resection (Cetinkaya et al , ), and in rats with portal hypertension (Topuz et al , ). Intriguingly, melatonin therapy exerted anti‐inflammatory effects but did not reduce neuronal injury in a rabbit model of either Gram‐positive Streptococcus pneumoniae or Gram‐negative Escherichia coli meningitis; these failures may be attributed to the 12 h delay in the administration of melatonin after the infection (Spreer et al , ).…”

Section: Defensive Effects Of Melatonin Against Bacterial Pathogensmentioning

confidence: 99%

“…In summary, a reduced expression of AA‐NAT and ASMT results in lower melatonin levels. The reduced melatonin levels may favour the translocation of bacteria and increase the incidence of infection; these changes are inhibited by melatonin administration (Cetinkaya et al , ; Sozen et al , ; Topuz et al , ) (Figure ). In summary, melatonin may serve as a novel antibiotic to defend against bacterial pathogens, and the possible mechanisms involve the suppression of NF‐κB and STAT1 (Figure B).…”

Section: Defensive Effects Of Melatonin Against Bacterial Pathogensmentioning

confidence: 99%

Utilizing melatonin to combat bacterial infections and septic injury

Deng

et al. 2017

British J Pharmacology

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*These authors contributed equally to this work.Melatonin, also known as N-acetyl-5-methoxytryptamine, is a ubiquitously acting molecule that is produced by the pineal gland and other organs of animals, including humans. As melatonin and its metabolites are potent antioxidants and free radical scavengers, they are protective against a variety of disorders. Moreover, multiple molecular targets of melatonin have been identified, and its actions are both receptor-mediated and receptor-independent. Recent studies have shown that melatonin may be useful in fighting against sepsis and septic injury due to its antioxidative and anti-inflammatory actions; the results generally indicate a promising therapeutic application for melatonin in the treatment of sepsis. To provide a comprehensive understanding regarding the protective effects of melatonin against septic injury, in the present review we have evaluated the published literature in which melatonin has been used to treat experimental and clinical sepsis. Firstly, we present the evidence from studies that have used melatonin to resist bacterial pathogens. Secondly, we illustrate the protective effect of melatonin against septic injury and discuss the possible mechanisms. Finally, the potential directions for future melatonin research against sepsis are summarized. AbbreviationsA-ADMSCs, adipose-derived mesenchymal stem cells; AA-NAT, arylalkylamine-N-acetyltransferase; ASMT, Nacetylserotonin O-methyltransferase; GPx, glutathione peroxidase; MDA, malondialdehyde; STAT1, signal transducer and activator of transcription 1; UPR, unfolded protein response

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“…Misoprostol, an FDA-approved synthetic prostaglandin E1 analog (PGE1), has mucosal cytoprotective and antisecretory effects and is also used off-label to induce labor. It has been shown that misoprostol inhibits bacterial translocation, modifies bacterial clearance in mice after a burn injury (61, 62), and has cytoprotectant properties against mucosal radiation (61, 62). Misoprostol has multiple uses with different combinations with lidocaine, metronidazole, pentoxifylline, and gentamicin as a wound healing agent for decubitus ulcers or diabetic foot lesions (63).…”

Section: Discussionmentioning

confidence: 99%

Prostaglandin E₂ production is required for phagocyte CXCR2-mediated skin host defense in obese and hyperglycemic mice

Klopsfenstein

Hibbs

Blackman

et al. 2022

Preprint

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Poorly controlled glucose observed in obese individuals with diabetes is associated with a significantly increased risk of infection, particularly in the skin and soft tissues. Staphylococcus aureus is a significant cause of skin and soft tissue infections (SSTIs) in obese and hyperglycemic individuals with growing antibiotic resistance making these infections difficult to treat. However, the events that drive dysregulated skin host defense during hyperglycemia remain to be fully elucidated. Here we examined how the prostaglandin E2 (PGE2) threshold impacts tissue injury and host defense during methicillin-resistant S. aureus (MRSA) skin infection in obese and hyperglycemic mice. Our data show that obesity and hyperglycemia are accompanied by impaired expression of prostaglandin E synthase 1 and PGE2 production in infected skin. Restoration of PGE2 levels with the PGE analog misoprostol improved infection outcomes in obese and hyperglycemic mice in a manner dependent on E prostanoid 3-mediated cAMP inhibition. Topical misoprostol restored the levels of CXC chemokines and CXCR2+ monocyte and neutrophil recruitment. Here, we are unveiling a defective signaling program that culminates in inadequate CXCR2 phagocyte migration to the infected skin of obese and hyperglycemic mice. Furthermore, these data also lead to a novel drug repurposing opportunity to treat antibiotic-resistant pathogens in hyperglycemic conditions.

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Effect of melatonin and misoprostol on bacterial translocation in portal hypertensive rats

Abstract: In this study, bacterial translocation occurred in portal hypertension. Melatonin and misoprostol reduced the incidence of bacterial translocation in portal hypertensive rats.

Cited by 7 publications

References 24 publications

Prevention of Rat Intestinal Injury with a Drug Combination of Melatonin and Misoprostol

Prevention of Rat Intestinal Injury with a Drug Combination of Melatonin and Misoprostol

Utilizing melatonin to combat bacterial infections and septic injury

Prostaglandin E₂ production is required for phagocyte CXCR2-mediated skin host defense in obese and hyperglycemic mice

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Effect of melatonin and misoprostol on bacterial translocation in portal hypertensive rats

Abstract: In this study, bacterial translocation occurred in portal hypertension. Melatonin and misoprostol reduced the incidence of bacterial translocation in portal hypertensive rats.

Cited by 7 publications

References 24 publications

Prevention of Rat Intestinal Injury with a Drug Combination of Melatonin and Misoprostol

Prevention of Rat Intestinal Injury with a Drug Combination of Melatonin and Misoprostol

Utilizing melatonin to combat bacterial infections and septic injury

Prostaglandin E2 production is required for phagocyte CXCR2-mediated skin host defense in obese and hyperglycemic mice

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Product

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Prostaglandin E₂ production is required for phagocyte CXCR2-mediated skin host defense in obese and hyperglycemic mice