Fasting-induced intestinal damage is mediated by oxidative and inflammatory responses

Abdeen, Suad; Mathew, T.C.; Khan, Islam Ullah; Dashti, H.; Asfar, Sami

doi:10.1002/bjs.6588

Cited by 11 publications

(15 citation statements)

References 32 publications

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“…Furthermore, Kruidenier et al reported that CuZnSOD staining is observed in the human intestinal epithelium [15], and Abdeen et al reported that SOD expression is high in the intestinal mucosa of the rat jejunum [1]. These results of reports are in agreement with the results of the present study on cecal histology and immunohistochemistry of CuZnSOD in GF and CV mice.…”

Section: Discussionsupporting

confidence: 92%

Upregulation of Superoxide Dismutase Activity in the Intestinal Tract Mucosa of Germ-Free Mice

Dobashi

Yoshimura

Atarashi

et al. 2013

The Journal of Veterinary Medical Science

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ABSTRACT. Superoxide dismutase (SOD) catalyzes the breakdown of superoxide into hydrogen peroxide and oxygen in the antioxidant defense system. We had reported that the SOD activities in the ceca of germ-free (GF) mice were significantly higher than those in conventional (CV) mice. In this study, we confirmed the location where SOD activity and protein expression increased in the ceca of GF mice. An immunohistochemical analysis and total SOD activity assay were conducted using the mucosa and other remaining tissues in the ceca. In addition to SOD activity in the ceca, 4 sites of intestinal (duodenal, jejunal, ileal and colonic) mucosae in GF mice were compared with those of CV mice. Total SOD activity in the cecal mucosa of GF mice was significantly higher than that in CV mice (P<0.01), and the intensity of CuZnSOD-positive cells in cecal mucosa was increased in all GF mice. Total and CuZnSOD activities in the duodenal, jejunal, ileal, cecal and colonic mucosae of GF mice were significantly higher than those in CV mice (P<0.05, or P<0.01). Furthermore, CuZnSOD mRNA showed similar tendencies with respect to these activities. Our results suggest for the first time that upregulation of SOD activity occurs in the entire intestinal mucosa of GF mice. Antioxidant enzymes play an important role in preventing oxidative stress by acting on reactive oxidative species (ROS) generated in vivo. While physiological concentrations of ROS in vivo are beneficial and involve cell signaling pathways and survival from invading pathogens, an unbalanced, elevated levels of ROS may contribute to the development of various diseases, such as cancer, hypertension, diabetes, atherosclerosis, inflammation, and premature aging [30]. Superoxide dismutases (SODs) [16] are the most important antioxidant enzymes in the antioxidant defense system against a ROS of superoxide (O 2•− ). At present, 3 distinct SOD isoforms have been identified in mammals. One SOD isoform has Cu and Zn in its catalytic center (CuZnSOD) and exists in the intracellular cytoplasmic compartment; the second SOD isoform has manganese (Mn) in its catalytic center (MnSOD) and exists in the mitochondria of aerobic cells; and the third isoform is an extracellular SOD [30]. SODs are the first line of defense for dismutation of excess O 2•− , which causes tissue disorders, as SODs convert O 2•− to molecular oxygen and H 2 O 2 [22]. Of the different SOD enzymes, CuZnSOD is the most abundant and widely distributed enzyme in many tissues [13].We recently reported that total SOD, CuZnSOD and MnSOD activities in the ceca of germ-free (GF) mice were significantly higher than those in the ceca of conventional (CV) mice [7]. CuZnSOD mRNA expression in the ceca of GF mice was significantly higher than that in CV mice, and CuZnSOD protein expression showed similar tendencies. Consistent with these results, the total SOD activity in conventionalized (CVz) mice decreased to the level of total SOD activity observed in the ceca of CV mice. These results suggested that the antioxidant defense ...

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Section: Discussionsupporting

confidence: 92%

Upregulation of Superoxide Dismutase Activity in the Intestinal Tract Mucosa of Germ-Free Mice

Dobashi

Yoshimura

Atarashi

et al. 2013

The Journal of Veterinary Medical Science

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“…Recent evidence shows that IEL-derived IFN-␥ evokes enterocyte apoptosis via an upregulation of Fas/FasL, leading to the increase in sensitivity of epithelial cells to Fas-mediated apoptosis (30,56) through the type 1 pathway (56). It has been suggested that complex reciprocal interactions exist between IEC and IEL (20,56); therefore, it is likely that IEC and IEL form a reciprocal feedback loop in which iNOS-released NO, physiologically present in IEC, stimulates IFN-␥ production in IEL through a ROS-mediated mechanism (1,5,38), then IFN-␥ stimulates further iNOS-derived NO production, resulting in further IFN-␥ production and subsequent IEC apoptosis (Fig. 13).…”

Section: Discussionmentioning

confidence: 99%

Fasting-induced intestinal apoptosis is mediated by inducible nitric oxide synthase and interferon-γ in rat

Ito

Uchida

Yokote

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

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Ito J, Uchida H, Yokote T, Ohtake K, Kobayashi J. Fastinginduced intestinal apoptosis is mediated by inducible nitric oxide synthase and interferon-␥ in rat. Am J Physiol Gastrointest Liver Physiol 298: G916 -G926, 2010. First published April 8, 2010 doi:10.1152/ajpgi.00429.2009 is associated with intestinal apoptosis in health and disease. This study aimed to investigate the role of intestinal NO in the regulation of apoptosis during fasting in rats. Male Wistar rats were divided into two groups and subcutaneously injected with saline (SA) or aminoguanidine (AG), followed by fasting for 24, 48, 60, and 72 h. At each time point, the jejunum was subjected to histological evaluation for enterocyte apoptosis by histomorphometric assessment and TUNEL analysis. We performed immunohistochemistry for inducible NO synthase (iNOS) expression in the jejunum and measured tissue nitrite levels using HPLC and 8-hydroxydeoxyguanosine adduct using ELISA, indicative of endogenous NO production and reactive oxygen species (ROS) production, respectively. Jejunal transcriptional levels of iNOS, neuronal NO synthase (nNOS), and interferon-␥ (IFN-␥) were also determined by RT-PCR. Fasting caused significant jejunal mucosal atrophy due to attenuated cell proliferation and enhanced apoptosis with increase in iNOS transcription, its protein expression in intestinal epithelial cells (IEC), and jejunal nitrite levels. However, AG treatment histologically reduced apoptosis with inhibition of fastinginduced iNOS transcription, protein expression, and nitrite production. We also observed fasting-induced ROS production and subsequent IFN-␥ transcription, which were all inhibited by AG treatment. Furthermore, we observed reduced transcriptional levels of nNOS, known to suppress iNOS activation physiologically. These results suggest that fasting-induced iNOS activation in IEC may induce apoptosis mediators such as IFN-␥ via a ROS-mediated mechanism and also a possible role of nNOS in the regulation of iNOS activity in fasting-induced apoptosis.aminoguanidine; reactive oxygen species; intestinal epithelial cells; neuronal nitric oxide synthase THE GASTROINTESTINAL EPITHELIUM is a dynamic tissue characterized by a high cellular turnover rate with a balance between cell proliferation and cell apoptosis, consequently leading to renewal of the entire intestinal epithelium every 3-5 days (9,19). This single layer of cells lining the gut lumen acts as a barrier against harmful intraluminal entities, including foreign antigens, microorganisms, and toxins, and also acts as a selective filter allowing the translocation of essential dietary nutrients, electrolytes, and water. However, these physiological functions are occasionally impaired under pathological conditions such as inflammation and ischemia-reperfusion and are accompanied by intestinal histological changes, including apoptosis.Fasting is likely a physiological challenge evoking a response to the absence of luminal nutrients by functional and morphological changes, including intestinal epithe...

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“…However, little is known about the interaction between intestinal microflora and antioxidant enzyme activity, although there have been some reports on leukocyte function with respect to either O 2 ·-release [18,20], gastrointestinal nitric oxide (NO) generation measurements [27], or expression of GPx, which is a different antioxidant enzyme, found in the cecal mucosa of GF animals as well as CV animals [15]. In the gastrointestinal tract, SOD activity has been reported to determine the therapeutic value of SOD in an experimental model [1,26], but the effect of intestinal microflora on antioxidant enzyme activity is still poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Effects of Intestinal Microflora on Superoxide Dismutase Activity in the Mouse Cecum

et al. 2011

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Abstract:In the antioxidant defense system, superoxide dismutase (SOD) catalyzes the breakdown of superoxide into hydrogen peroxide and oxygen. In the cecum, the influence of intestinal microflora on SOD activity is unknown. In this study, we used germ-free (GF) mice to examine the effect of intestinal microflora on SOD activity in the cecum, and SOD activity was compared between GF and conventional (CV) mice. The activity of CuZnSOD and MnSOD was determined using the SOD Assay Kit-WST. Expressions of CuZnSOD mRNA and protein were determined by real-time PCR and western blot analyses, respectively. The activities of CuZnSOD and MnSOD were significantly higher in the ceca of GF IQI and FVB/N strain mice than in CV mice (P<0.01-0.05). The gene expressions of CuZnSOD mRNA in the ceca of GF mice were significantly higher than those in CV mice (P<0.05), and CuZnSOD protein expression showed similar tendencies. Consistent with the abovementioned results, the total SOD activity in conventionalized mice decreased to the level of total SOD activity observed in the ceca of CV mice. Furthermore, no differences between GF and CV mice were observed in the SOD activities in the liver and thymus. Our results suggest that the antioxidant defense system in the mouse cecum is influenced by the intestinal microflora that downregulate SOD activity.

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Fasting-induced intestinal damage is mediated by oxidative and inflammatory responses

Abstract: Green tea reverses the fasting-induced damage to the intestinal mucosa by its antioxidant and anti-inflammatory effect.

Cited by 11 publications

References 32 publications

Upregulation of Superoxide Dismutase Activity in the Intestinal Tract Mucosa of Germ-Free Mice

Upregulation of Superoxide Dismutase Activity in the Intestinal Tract Mucosa of Germ-Free Mice

Fasting-induced intestinal apoptosis is mediated by inducible nitric oxide synthase and interferon-γ in rat

Effects of Intestinal Microflora on Superoxide Dismutase Activity in the Mouse Cecum

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