Protective effect of metronidazole on uncoupling mitochondrial oxidative phosphorylation induced by NSAID: a new mechanism

Leite, André Z.

doi:10.1136/gut.48.2.163

Cited by 41 publications

(45 citation statements)

References 67 publications

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“…MTZ has a beneficial effect on intestinal inflammation and reduces colonic permeability 11 to bacterial endotoxins. It may inhibit endotoxin-induced tumor necrosis factor alpha production, activation of Kupffer cells and portal tract macrophages, and secretion of chemokines and cytokines by biliary epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…10 Metronidazole also has beneficial effects in healing intestinal damage, reduces intestinal permeability, and has a direct protective effect on the uncoupling of mitochondrial oxidative phosphorylation caused by nonsteroidal anti-inflammatory drugs. 11 At this time no effective medical therapy is available for treatment of PSC. Various treatment strategies have been evaluated in PSC and negative studies have been published on glucocorticoids, budesonide, azathioprine, colchicine, cyclosporine, D-penicillamine, methotrexate, tacrolimus, and pentoxifyllene 12 and in a small series even in combination with ursodeoxycholic acid (UDCA).…”

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confidence: 99%

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Metronidazole and ursodeoxycholic acid for primary sclerosing cholangitis: A randomized placebo-controlled trial

et al. 2004

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No effective medical therapy is currently available for primary sclerosing cholangitis (PSC). Ursodeoxycholic acid (UDCA) improves liver enzymes, but its effect on liver histology is controversial. Metronidazole (MTZ) prevents PSC-like liver damage in animal models and reduces intestinal permeability. We recruited 80 patients with PSC into a randomized placebo-controlled study to evaluate the effect of UDCA and MTZ (UDCA/MTZ) compared with UDCA/placebo on the progression of PSC. Patients (41 UDCA/placebo and 39 UDCA/ MTZ) were followed every third month. Assessment of liver function test, histological stage and grade, and cholangiography (via ERCP) at baseline showed no differences between the groups. After 36 months, serum aminotransferases ␥-glutamyltransferase, and alkaline phosphatase (ALP) decreased markedly in both groups, serum ALP more significantly in the UDCA/MTZ group (؊337 ؎ 54 U/L, P < .05) compared with the UDCA/placebo group. The New Mayo Risk Score decreased markedly only in the UDCA/MTZ group (؊0.50 ؎ 0.13, P < .01). The number of patients with improvement of stage (P < .05) and grade (P < .05) was higher in the combination group. ERCP findings showed no progression or improvement in 77% and 68% of patients on UDCA/MTZ and UDCA/placebo, respectively. In conclusion, combining MTZ with UDCA in PSC improved serum ALP levels and New Mayo Risk Score, but no statistically significant effect on disease progression as assessed via liver histology or ERCP was seen. Long-term studies using a higher dose of UDCA combined with MTZ in larger patient populations are indicated. (HEPATOLOGY 2004;40:1379 -1386

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Metronidazole and ursodeoxycholic acid for primary sclerosing cholangitis: A randomized placebo-controlled trial

et al. 2004

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“…[52] метрони-дазол предотвращал повреждение тонкой кишки индометацином у крыс путем прямого влияния на разобщение окислительного фосфорилирования в митохондриях. По данным G. Davies и со-авт.…”

Section: терапевтический архив 12 2014unclassified

Antiplatelet therapy with acetylsalicylic acid: Approaches to reducing the frequency of gastrointenstinal adverse reactions

Ev¹

2014

Ter. arkh.

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Антитромбоцитарная терапия (АТТ) ингибитором синтеза тромбоксана А 2 -ацетилсалициловой кислотой (АСК) -высоко эффективна для профилактики сердечно-сосудистых осложне-ний (ССО). Между тем снижение риска развития кардиологиче-ских событий достигается путем повышения вероятности неже-лательных реакций со стороны органов пищеварения.Прием АСК традиционно связывают с поражением прокси-мальных отделов (ПО) желудочно-кишечного тракта (ЖКТ). При длительной терапии низкими дозами АСК частота развития симптомов диспепсии достигает 15-40% [1], эрозивного эзофа-гита -7,9-22%, язв пищевода -0,9% [2,3], эрозий желудка и/ или двенадцатиперстной кишки (ДПК) -34-63,1% [4,5], язв желудка и/или ДПК -10-40% [6]. Относительный риск (ОР) желудочно-кишечных кровотечений (ЖКК) варьирует, по расче-там различных авторов, в пределах от 2,4 до 7,7 [7,8]. Показатель выше в случаях приема АСК для первичной по сравнению с вто-ричной профилактикой ССО [9].Между тем благодаря внедрению в клиническую практику новых методов диагностики появились сведения о поражении АСК дистальных отделов (ДО) пищеварительного тракта. Назна-чение АСК в дозе 100 мг/сут здоровым добровольцам привело через 2 нед к повреждению слизистой оболочки (СО) тонкой АннотацияПрием ацетилсалициловой кислоты (АСК) высокоэффективен для профилактики сердечно-сосудистых осложнений, но сопряжен с повышением вероятности нежелательных явлений со стороны органов пищеварения. В статье представлены современные данные по эпидемиологии, механизмам развития и факторам риска эзофагогастродуодено-и энтеропатий на фоне длительной терапии низкими дозами АСК. Изложены ключевые принципы их профилактики. Ключевые слов: ацетилсалициловая кислота, ингибиторы протонной помпы, эрадикационная терапия.Acetylsalicylic acid (ASA) is highly effective in preventing cardiovascular events, but associated with increased risk for digestive adverse reactions. The paper provides an update on the epidemiology, mechanisms, and risk factors of esophagogastroduodenoand enteropathies during long-term low-dose ACA therapy. It outlines the key principles of their prevention. Key words: acetylsalicylic acid, proton pump inhibitors, eradication therapy.ИМ -инфаркт миокарда НПВП -нестероидные противовоспалительные препараты ОР -относительный риск ОШ -отношение шансов ПО -проксимальные отделы РКИ -рандомизированное клиническое исследование СО -слизистая оболочка ССО -сердечно-сосудистые осложнения ЦОГ-1 -циклооксигеназа-1 ЯБ -язвенная болезнь кишки, визуализированному с помощью капсульной эндоско-пии, в 50% случаев. По сравнению с исходным уровень фекаль-ного кальпротектина (показателя, коррелирующего с гистологи-ческой и эндоскопической активностью воспаления стенки киш-ки) повысился в 4 раза, а коэффициента лактулоза/маннитол (теста на проницаемость кишечной стенки, отражающего ба-рьерную функцию кишечной стенки) -в 1,7 раза [10]. Применяя капсульную эндоскопию для уточнения происхождения ЖКК и/ или болевого абдоминального синдрома у лиц, получавших низ-кие дозы АСК более 3 мес, H. Endo и соавт.[11] в 63,6% случаев выя...

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“…Koga et al [32] reported that oral pretreatment of rats with kanamycin, which targets Gram-negative bacteria, dose-dependently prevented the small intestinal injury induced by indomethacin. Leite et al [33] reported protective effects against indomethacin-induced enteropathy by metronidazole, which is effective at killing Gram-negative and Gram-positive anaerobes. However, these treatments have not been found to be consistently effective [30].…”

Section: Do Antibiotics Prevent Nsaid Enteropathy?mentioning

confidence: 99%

NSAID enteropathy and bacteria: a complicated relationship

et al. 2015

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The clinical significance of small intestinal damage caused by nonsteroidal anti-inflammatory drugs (NSAIDs) remains under-appreciated. It occurs with greater frequency than the damage caused by these drugs in the upper gastrointestinal tract, but is much more difficult to diagnose and treat. Although the pathogenesis of NSAID enteropathy remains incompletely understood, it is clear that bacteria, bile, and the enterohepatic circulation of NSAIDs are all important factors. However, they are also interrelated with one another. Bacterial enzymes can affect the cytotoxicity of bile and are essential for enterohepatic circulation of NSAIDs. Gram-negative bacteria appear to be particularly important in the pathogenesis of NSAID enteropathy, possibly through release of endotoxin. Inhibitors of gastric acid secretion significantly aggravate NSAID enteropathy, and this effect is due to significant changes in the intestinal microbiome. Treatment with antibiotics can, in some circumstances, reduce the severity of NSAID enteropathy, but published results are inconsistent. Specific antibiotic-induced changes in the microbiota have not been causally linked to prevention of intestinal damage. Treatment with probiotics, particularly Bifidobacterium, Lactobacillus, and Faecalibacteriaum prausnitzii, has shown promising effects in animal models. Our studies suggest that these beneficial effects are due to colonization by the bacteria, rather than to products released by the bacteria.

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Protective effect of metronidazole on uncoupling mitochondrial oxidative phosphorylation induced by NSAID: a new mechanism

Cited by 41 publications

References 67 publications

Metronidazole and ursodeoxycholic acid for primary sclerosing cholangitis: A randomized placebo-controlled trial

Metronidazole and ursodeoxycholic acid for primary sclerosing cholangitis: A randomized placebo-controlled trial

Antiplatelet therapy with acetylsalicylic acid: Approaches to reducing the frequency of gastrointenstinal adverse reactions

NSAID enteropathy and bacteria: a complicated relationship

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