Oxidative stress controlling agents are effective for small intestinal injuries induced by non‐steroidal anti‐inflammatory drugs

Kono, Yoshiyasu; Takaki, Akinobu; Shimomura, Yuki; Onji, Masahiro; Ishikawa, Hisashi; Takahashi, Sakuma; Horii, Joichiro; Kobayashi, Sayo; Kawai, Daisuke; Yamamoto, Kazuhide; Okada, Hiroyuki

doi:10.1111/jgh.13424

Cited by 8 publications

(5 citation statements)

References 34 publications

(57 reference statements)

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“…It has been reported that the use of aspirin inhibits the production of ROS in cells exposed to oxidized-LDL [72]. Together, aspirin and NSAIDs are involved in the regulation of ROS and RNS to prevent cellular damage and inflammation [72,73,74,75]. However, these functions have become controversial as recent studies also suggest that these drugs may increase the levels of oxidized proteins resulting from OS.…”

Section: Resultsmentioning

confidence: 99%

A Review of A Priori Defined Oxidative Balance Scores Relative to Their Components and Impact on Health Outcomes

et al. 2019

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Oxidative Balance Scores (OBSs) are tools that have emerged to evaluate the global balance of individuals’ oxidation—reduction status. The aim was to compare OBSs available in the literature regarding their characteristics and associations with chronic diseases in epidemiological studies. Studies that developed OBSs were searched in PubMed until August 2018. A total of 21 OBSs were identified. These OBSs presented different scoring schemes and different types of anti- and pro-oxidant components, including dietary factors (dietary intake and/or nutrient biomarkers), lifestyle factors, and medications. Most OBSs were based on over 10 components, and some included only dietary factors. Few considered weighted components in the score. Only three OBSs were validated as potential surrogates of oxidative balance through inflammation and OS-related biomarkers. Notably, all the OBSs were associated—to a varying degree—with a reduced risk of cardiovascular diseases, chronic kidney disease, colorectal adenomas, and different cancer types (colorectal and breast cancer), as well as with all-cause and cancer-related mortality. For other outcomes, e.g., prostate cancer, contradictory results were reported. In summary, there is a great heterogeneity in the definition of OBSs. Most studies are concordant in supporting that excessive OS reflected by a lower OBS has deleterious effects on health. Unified criteria for defining the proper OBSs, valuable to gauge OS-related aspects of the diet and lifestyle that may lead to adverse health outcomes, are needed.

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Section: Resultsmentioning

confidence: 99%

A Review of A Priori Defined Oxidative Balance Scores Relative to Their Components and Impact on Health Outcomes

et al. 2019

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“…From a mechanistic point of view, NSAIDs have been reported to damage GI epithelial cells by inducing mitochondrial dysfunction that includes the inhibition of complex I, uncoupling of oxidative phosphorylation, inhibition of oxygen consumption, and a decrease in intracellular ATP. − These cell-damaging effects are closely associated with the massive formation of reactive oxygen species (ROS). , In vitro studies , carried out in human intestinal cell monolayers (T84 and Caco-2) reveal that mitochondrial dysfunction and oxidative stress generated by NSAIDs cause an alteration in the distribution of certain tight junction proteins that may induce an increase in paracellular permeability. Studies conducted in vivo indicate that the increase in ROS induced by NSAIDs is associated with alterations in the GI barrier function in rats , and humans . Additionally, it has been suggested that NSAIDs can also induce damage to the GI mucosa by promoting a proinflammatory effect through the activation of nuclear factor kappa B (NF-kB). , The inflammatory response effect may be accompanied by an increase in the expression of proinflammatory cytokines such as IL-8 …”

Section: Introductionmentioning

confidence: 99%

Quercetin Oxidation Metabolite Present in Onion Peel Protects Caco-2 Cells against the Oxidative Stress, NF-kB Activation, and Loss of Epithelial Barrier Function Induced by NSAIDs

Fuentes

Camargo

Atala

et al. 2021

J. Agric. Food Chem.

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The potential of 2-(3,4-dihydroxybenzoyl)-2,4,6-trihydroxy-3(2H)-benzofuranone (BZF), a quercetin oxidation metabolite, and that of a BZF-rich onion peel aqueous extract (OAE) to protect Caco-2 monolayers against the oxidative stress (OS) and an increased permeability (IP) induced by five nonsteroidal anti-inflammatory drugs (NSAIDs) (indomethacin, diclofenac, piroxicam, ibuprofen, and metamizole) were investigated. Under identical OS conditions, the NSAIDs substantially differed in their ability to induce an IP and/or NF-kB activation. The OAE (100 nM BZF) protected in identical magnitude (84–86%) against OS but in a highly dissimilar manner against the IP (18–73%). While all NSAIDs activated NF-kB, the OAE prevented only that induced by indomethacin. Results reveal that the IP has no direct relationship with the OS and that with the exception of indomethacin, the prevention of NSAIDs-induced OS and/or NF-kB activation plays no fundamental role in the IP-protecting effect of OAE. These results warrant the in vivo evaluation of OAE against indomethacin-induced loss of intestinal barrier function.

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“…Therefore, we further included the factors mentioned in the literature that may affect the production of ROS in the body via multiple linear regression to exclude the influence of these factors on the results. The factors involved include the use of NSAIDs [ 33 ], heavy metals (lead, cadmium) [ 34 ] and environmental toxicants (benzene, toluene) [ 35 ]. The results of the sensitivity analysis were consistent with those of the main analysis (Table 5 ).…”

Section: Resultsmentioning

confidence: 99%

The relationship between oxidative balance scores and chronic diarrhea and constipation: a population-based study

Hu,

Zou,

Qiao

et al. 2024

BMC Public Health

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Background Oxidative stress is closely related to gut health. Exposures to oxidative stress in one’s diet and lifestyle can be evaluated by the oxidative balance score (OBS). However, the relationship between OBS and intestinal habits is unknown. This study aimed to investigate the relationships between OBS and intestinal habits (chronic diarrhea and chronic constipation) and the underlying mechanisms involved. Methods Using data from the National Health and Nutrition Examination Survey (NHANES) database from 2005 to 2010, we included a total of 8065 participants. Twenty dietary and lifestyle factors were selected for the OBS calculates. Chronic constipation and chronic diarrhea were defined using the Bristol stool form scale (BSFS) types 1 and 2 and the BSFS 6 and 7, respectively. Multivariate logistic regression, subgroup analysis, and restricted cubic splines (RCS) analysis were used to evaluate the relationship between OBS and defecation habits. Finally, we used mediation analysis to explore the indirect effects of oxidative stress and inflammatory markers on these associations. Results After adjusting for all the covariates, multivariate logistic regression analysis revealed that OBS was negatively correlated with diarrhea (OR = 0.57; 95%CI = 0.39–0.83; P = 0.008)and positively correlated with constipation (OR = 1.75; 95%CI = 1.19–2.25; P = 0.008). The RCS showed a nonlinear relationship between OBS and diarrhea (P for nonlinearity = 0.02) and a linear relationship between OBS and constipation (P for nonlinearity = 0.19). Mediation analysis showed that the C-reactive protein (CRP) concentration and white blood cell (WBC) count mediated the correlation between OBS and diarrhea by 6.28% and 6.53%, respectively (P < 0.05). Conclusions OBS is closely related to changes in patients' defecation habits. Oxidative stress and inflammation may play a role in the relationship between the two. This result emphasizes the importance of the public adjusting their lifestyle and dietary habits according to their own situation. However, further prospective studies are needed to analyze the relationship between oxidative stress and changes in defecation habits.

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Oxidative stress controlling agents are effective for small intestinal injuries induced by non‐steroidal anti‐inflammatory drugs

Abstract: Non-aspirin NSAID-induced intestinal ulcers are related to decreased anti-oxidative stress function. Anti-oxidants, especially L-carnitine, are good candidates for intestinal ulcers.

Cited by 8 publications

References 34 publications

A Review of A Priori Defined Oxidative Balance Scores Relative to Their Components and Impact on Health Outcomes

A Review of A Priori Defined Oxidative Balance Scores Relative to Their Components and Impact on Health Outcomes

Quercetin Oxidation Metabolite Present in Onion Peel Protects Caco-2 Cells against the Oxidative Stress, NF-kB Activation, and Loss of Epithelial Barrier Function Induced by NSAIDs

The relationship between oxidative balance scores and chronic diarrhea and constipation: a population-based study

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