Minocycline attenuates 5-fluorouracil-induced small intestinal mucositis in mouse model

Huang, Tseng; Chu, Heng-Cheng; Lin, Yi-Ling; Ho, Whae-Hong; Hou, Hsien-San; Chao, You‐Chen; Liao, Ching‐Len

doi:10.1016/j.bbrc.2009.09.041

Cited by 54 publications

(43 citation statements)

References 24 publications

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“…There is no evidence to rule out either possibility at the present time, since minocycline can freely cross the blood-brain barrier 26 and can directly influence both the gut and the brain. Minocycline has profound effects on the gut: (1) it inhibits expression of pro-inflammatory cytokines and intestinal damage in mouse model of colitis 51, 52 , (2) it attenuates gut damage and intestinal mucositis due to cancer chemotherapy 53 , and (3) our data show it improves gut microbial homeostasis during HTN dysbiosis and is able to rebalance the gut acetate-, butyrate-, and lactate-producing bacterial populations. Furthermore, evidence also exists of direct anti-inflammatory effects of minocycline in the brain in many neurodegenerative and neurobehavioral diseases 54, 55 .…”

Section: Discussionmentioning

confidence: 75%

Gut Dysbiosis Is Linked to Hypertension

Yang¹,

Santisteban²,

Rodríguez³

et al. 2015

Hypertension

1,163

1,124

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Emerging evidence suggests that gut microbiota is critical in the maintenance of physiological homeostasis. The present study was designed to test the hypothesis that dysbiosis in gut microbiota is associated with hypertension since genetic, environmental, and dietary factors profoundly influence both gut microbiota and blood pressure. Bacterial DNA from fecal samples of two rat models of hypertension and a small cohort of patients was used for bacterial genomic analysis. We observed a significant decrease in microbial richness, diversity, and evenness in the spontaneously hypertensive rat, in addition to an increased Firmicutes to Bacteroidetes ratio. These changes were accompanied with decreases in acetate- and butyrate-producing bacteria. Additionally, the microbiota of a small cohort of human hypertension patients was found to follow a similar dysbiotic pattern, as it was less rich and diverse than that of control subjects. Similar changes in gut microbiota were observed in the chronic angiotensin II infusion rat model, most notably decreased microbial richness and an increased Firmicutes to Bacteroidetes ratio. In this model, we evaluated the efficacy of oral minocycline in restoring gut microbiota. In addition to attenuating high blood pressure, minocycline was able to rebalance the dysbiotic hypertension gut microbiota by reducing the Firmicutes to Bacteroidetes ratio. These observations demonstrate that high BP is associated with gut microbiota dysbiosis, both in animal and human hypertension. They suggest that dietary intervention to correct gut microbiota could be an innovative nutritional therapeutic strategy for hypertension.

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Section: Discussionmentioning

confidence: 75%

Gut Dysbiosis Is Linked to Hypertension

Yang¹,

Santisteban²,

Rodríguez³

et al. 2015

Hypertension

1,163

1,124

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“…16) It has been reported that 5-FU induced iNOS expression in mice intestinal mucositis model. 17) 5-FU injection increased the iNOS-positive cell density in the small intestine signifi- The apoptotic death was defined as the average number and density of TUNEL-positive cells in 10 randomly fields from each sections at ×400 magnification. Each bar represents the mean±S.E.…”

Section: )mentioning

confidence: 99%

Rebamipide Attenuates 5-Fluorouracil-Induced Small Intestinal Mucositis in a Mouse Model

Kim

Moon

et al. 2015

Biological & Pharmaceutical Bulletin

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5-Fluorouracil (5-FU)-induced intestinal mucositis is one of the most common morbidities in chemother-apy and involves the reactive oxygen species (ROS) system, apoptosis, and inflammatory cytokines. Rebamipide exerts a mucosal-protective effect, mediated through several mechanisms. The aim of this study was to evaluate the effects of rebamipide in 5-FU-induced mouse small-intestinal mucositis. BALB/c mice were assigned randomly to four groups; (1) control group (n 10; receiving saline orally for 6 d), (2) Key words mucositis; 5-fluorouracil; small intestine; rebamipide 5-Fluorouracil (5-FU) is a cytostatic agent that has been used widely in the treatment of various solid tumors for more than 20 years. It is still considered to be among the most effective anti-neoplastic agents in advanced colorectal cancer and malignancies of the head and neck.1) Many non-chromatographic and chromatographic methods for the quantitation of 5-FU, related pro-drugs, and metabolites in biological matrices have been developed over the last 30 years to support preclinical and clinical studies.2) Nevertheless, 50-80% of patients who undergo 5-FU chemotherapy show clinical manifestations of mucositis, symptoms of which include severe diarrhea.2) Its incidence in patients who underwent standarddose chemotherapy was 40%, while it approached 100% in patients treated with high-dose chemotherapy.3)The pathophysiological mechanism of 5-FU-induced mucositis comprises five phases 4)

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“…Body weight loss, diarrhoea and villi measurements were improved by minocycline treatment, which also repressed the expression of TNFa, IL-1b and iNOS, decreased the apoptotic index, and inhibited PARP-1 activity in the mouse small intestine. In addition, minocycline treatment appeared to enhance the anti-tumour effects of 5-fluorouracil in tumour CT-26 xenograft mice (Huang et al, 2009a).…”

Section: Effects Of Minocycline On Cancermentioning

confidence: 99%

Minocycline: far beyond an antibiotic

Garrido-Mesa

Zarzuelo

Gálvez

2013

British J Pharmacology

761

597

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Minocycline is a second‐generation, semi‐synthetic tetracycline that has been in therapeutic use for over 30 years because of its antibiotic properties against both gram‐positive and gram‐negative bacteria. It is mainly used in the treatment of acne vulgaris and some sexually transmitted diseases. Recently, it has been reported that tetracyclines can exert a variety of biological actions that are independent of their anti‐microbial activity, including anti‐inflammatory and anti‐apoptotic activities, and inhibition of proteolysis, angiogenesis and tumour metastasis. These findings specifically concern to minocycline as it has recently been found to have multiple non‐antibiotic biological effects that are beneficial in experimental models of various diseases with an inflammatory basis, including dermatitis, periodontitis, atherosclerosis and autoimmune disorders such as rheumatoid arthritis and inflammatory bowel disease. Of note, minocycline has also emerged as the most effective tetracycline derivative at providing neuroprotection. This effect has been confirmed in experimental models of ischaemia, traumatic brain injury and neuropathic pain, and of several neurodegenerative conditions including Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Alzheimer's disease, multiple sclerosis and spinal cord injury. Moreover, other pre‐clinical studies have shown its ability to inhibit malignant cell growth and activation and replication of human immunodeficiency virus, and to prevent bone resorption. Considering the above‐mentioned findings, this review will cover the most important topics in the pharmacology of minocycline to date, supporting its evaluation as a new therapeutic approach for many of the diseases described herein.

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Minocycline attenuates 5-fluorouracil-induced small intestinal mucositis in mouse model

Cited by 54 publications

References 24 publications

Gut Dysbiosis Is Linked to Hypertension

Gut Dysbiosis Is Linked to Hypertension

Rebamipide Attenuates 5-Fluorouracil-Induced Small Intestinal Mucositis in a Mouse Model

Minocycline: far beyond an antibiotic

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