Research article
Feeding with olive oil attenuates inflammation in dextran sulfate sodium-induced colitis in rat☆

https://doi.org/10.1016/j.jnutbio.2013.10.005Get rights and content

Abstract

Chronic inflammation of long-term ulcerative colitis contributes to an increased risk of colon cancer. Few studies address whether extra-virgin olive oil (EVOO) intake suppresses inflammation, cell proliferation and signal transducers and activators of transcription (STAT) in the experimental colitis model. The aim of this study was to assess whether a 5% EVOO suppressed inflammation, increased cell proliferation and the expressions of STAT3 and STAT3 phosphorylation (pSTAT3) in dextran sulfate sodium (DSS)-induced colitis. Rats were administered DSS via drinking water (weight percentage: 4%) for 1 week with a 1-week recovery period for three cycles. Rats were divided into three groups: control group, standard diet without DSS; DSS group, standard diet+DSS; and DSS+EVOO group, EVOO diet (weight percentage: 5%)+DSS. Rats were sacrificed 5 weeks after DSS was first administered, and colonic damage was histologically and biochemically evaluated. As a result, chronic feeding of 5% EVOO attenuated inflammation. This was evaluated using a disease activity index, body weight loss and a histological score. Enhanced expressions of STAT3, pSTAT3, COX-2 and iNOS by DSS was attenuated by EVOO. In addition, EVOO attenuated increases in cell proliferation (PCNA) caused by DSS and recovered decreases in apoptosis (cleaved caspase-3). In conclusion, the study indicated that chronic feeding of 5% EVOO inhibited chronic inflammation in DSS-induced colitis in rats and also attenuated cell proliferation and recovered apoptosis in DSS colitis.

Introduction

Inflammatory bowel disease (IBD) includes two major chronic intestinal disorders: ulcerative colitis (UC) and Crohn’s disease (CD). The prevalence of IBD is increasing in developed countries, and one of the most serious complications of IBD is colorectal cancer (CRC) [1]. The risk of colitis-associated CRC is increased after long disease duration, especially in patients with chronic active disease [2]. Although many studies suggested that chronic inflammation might be positively correlated to the development of IBD-related carcinogenesis, the mechanisms of the IBD-related carcinogenesis process are not completely understood [3].

Many epidemiological studies indicate that dietary fat intake was a promoting factor for the incidence of CRCs [4], [5]. These studies are supported by several animal studies showing that a chronic high-fat diet enhanced carcinogenesis of CRCs [6], [7], [8], [9], [10], [11]. In contrast, chronic feeding of several types of fat, including fish oil and olive oil, diminish carcinogenesis of CRCs, which has been demonstrated by epidemiological studies [12], [13] and in vivo and/or in vitro studies [8], [14], [15], [16]. Our previous study indicated that dietary olive oil intake inhibited formation of aberrant crypt foci and mucosal arachidonate concentrations in azoxymethane (AOM)-induced CRCs in rats [8]. Other report has indicated that hydroxytyrosol (HT) isolated from olive oil inhibited cancer cell proliferation by inducing cell apoptosis and cell cycle arrest [17].

There have been some studies that investigated the effects of dietary fat, such as n-3, n-6 and n-9 polyunsaturated fatty acids, in IBD [18], [19], [20], [21], [22], [23], [24], [25], [26]. However, the effect of n-9 polyunsaturated fatty acids, such as olive oil, in experimental colitis is not very clear.

Cytokine signaling pathways involving transcription factors of the signal transducers and activators of transcription (STAT) family play a key role in the pathogenesis of IBD. STAT proteins are latent cytoplasmic transcription factors that induce transcription upon phosphorylation, dimerization and nuclear translocation. STAT3 and phospho-STAT3 (pSTAT3) levels were significantly increased in UC patients compared with controls [27].

Inflammation-related enzymes, including cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), are indicated to be key predisposing factors to CRCs [23], and COX-2 and iNOS expressions was closely associated with the development of cancers [28], [29].

Dextran sulfate sodium (DSS), with or without AOM, induced colon carcinogenesis in rodents [23], [30], [31], and the feeding of DSS enhanced cell proliferation [32]. Equability between cell proliferation and apoptosis was closely correlated to colon inflammation and carcinogenesis, as demonstrated in UC in humans and the experimental colitis model [33], [34], [35].

The aim of the present study was to demonstrate whether feeding with olive oil to rats suppressed inflammation, cell proliferation, STAT3 and pSTAT3 induced by oral administration of DSS for 1 week at a time followed by a 1-week recovery period and repeated three times.

Section snippets

Experimental animals and diets

Six-week-old male Sprague–Dawley rats (Japan CLEA Inc., Tokyo, Japan) were housed in an air-conditioned room that was maintained at 24°C–25°C, with constant humidity and an alternating 12-h light/dark cycle. All rats had access to food and water ad libitum. The base diet was standard laboratory diet AIN 76 (NOSAN, Kanagawa, Japan). Five percent extra-virgin olive oil (EVOO) (Ajinomoto, Tokyo, Japan) was added to diet AIN (weight percentage: 5%). EVOO contained 125±25 mg/kg total phenolics. HT

Effect of olive oil diet on DAI score in DSS-induced colitis

DAI score (Fig. 2) refers to external signs of colitis, indicating that DSS drinking induced symptoms of colitis at the beginning of week 3 and the DAI score increased in a time-dependent manner. Increases in the DAI score induced by DSS drinking were significantly attenuated by feeding with 5% olive oil (P<.01).

Total DSS drinking, diet consumption and body weight in DSS-induced colitis

DSS drinking was the same in the two groups (data not shown). Regarding diet consumption, the DSS+EVOO group significantly took diet more compared with control and DSS groups (data not

Discussion

This study indicates that chronic feeding of a 5% olive oil diet for 5 weeks attenuates inflammation in DSS-induced colitis of rat colons. This finding is based on evaluation using the DAI score, body weight loss, histological scores, STAT3, pSTAT3, COX-2 and iNOS.

There have been some studies that investigated the effects of dietary fat, such as n-3, n-6 and n-9 polyunsaturated fatty acids, in IBD [18], [19], [20], [21], [22], [23], [24], [25], [26]. With regard to n-9 polyunsaturated fatty

Acknowledgments

The authors thank Prof. Hitoshi Kawano and Ms. Yumiko Tsugitomi for their invaluable advice. This work was supported in part by Grants-in-Aid for Scientific Research from Japan Society for the Promotion of Science (KAKEN) 20590728, (KF) 24590889 and (RI) 20590745.

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    Conflicts of interest: The authors declare that there are no conflicts of interest.

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