Western-Style Diets Induce Oxidative Stress and Dysregulate Immune Responses in the Colon in a Mouse Model of Sporadic Colon Cancer

Erdelyi, Ildiko; Levenkova, Natasha; Lin, Elaine Y.; Pinto, John T.; Lipkin, Martin; Quimby, Fred W.; Holt, Peter R.

doi:10.3945/jn.108.104125

Cited by 78 publications

(67 citation statements)

References 36 publications

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“…Mice with blood glucose lower than 250 mg/dL were excluded from the experiment. Mice of all groups were housed in cages and received normal diet and tap water ad libitum in a constant environment (room temperature 25 ± 2°C, room humidity 50 ± 5%) with a 12 h light, 12 h dark cycle until being changed to a synthetic high-fat (HF) diet containing 21% (w/w, or 45% calories) fat, 0.05% cholesterol, 20% sucrose (Research Diets, Inc., New Brunswick, NJ, USA) [19] with or without 500 mg/kg PA purchased from Bioline Company, England [15]. Bodyweights and blood glucose levels were measured regularly.…”

Section: Methodsmentioning

confidence: 99%

“…Mice were rendered diabetic by intraperitoneal administration of low doses of STZ over 5 days, an established approach for inducing type-1 diabetes mellitus [18]. Given the previous features, STZ-induced diabetic apoE−/mice fed high-fat diet were used in our studies to accelerate DN and probe the role of dyslipidemia in DN development [19]. …”

Section: Introductionmentioning

confidence: 99%

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Proanthocyanidin Attenuation of Oxidative Stress and NF-κB Protects Apolipoprotein E-Deficient Mice against Diabetic Nephropathy

Al-Malki

Sayed

Rabey

2013

Evidence-Based Complementary and Alternative Medicine

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Hyperlipidemia and hyperglycemia result in oxidative stress and play a major role in the development of diabetic nephropathy (DN). We explored the effects of proanthocyanidin (PA) on the induction and progression of DN in apolipoprotein E-deficient mice. Diabetes Mellitus was induced in ten-week-old male apoE−/−mice using streptozotocin (STZ). Mice were fed with a high-fat diet in presence or absence of PA. PA treatment significantly reduced the high cholesterol levels, restored renal functions, and reduced albuminuria in the PA-treated diabetic mice compared with the diabetic untreated mice. In addition, the glomerular mesangial expansion in the diabetic mice was attenuated as a result of PA supplementation. Moreover, PA treatment restored the elevated levels of MDA and CML and the reduced activity of SOD and GSH in the diabetic mice. Furthermore, PA feeding reduced the activation and translocation of NF-κB to the nucleus compared with the diabetic untreated animals. Reduction of NF-κB activation resulted in the attenuation of the expression of IL-6, TGFβ, and RAGE which protected PA-treated mice against DN. The renoprotective effects of PA were found to be time independent regardless of whether the dietary feeding with PA was started pre-, co-, or post-STZ injection. In conclusion, part of the beneficial effects of PA includes the disruption of the detrimental AGE-RAGE-NFκB pathways.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Proanthocyanidin Attenuation of Oxidative Stress and NF-κB Protects Apolipoprotein E-Deficient Mice against Diabetic Nephropathy

Al-Malki

Sayed

Rabey

2013

Evidence-Based Complementary and Alternative Medicine

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“…Mice were rendered diabetic by intraperitoneal (IP) administration of low doses of STZ over 5 days, an established approach for inducing type 1 diabetes mellitus (Kromann et al ., 1982). Given the above features, STZ-induced diabetic ApoE−/− mice fed high fat diet were used in our studies to accelerate DN and probe the role of dyslipidemia in DN development (Erdely, et al, 2009; Cui, et al, 2009; Kasiske et al (1990)). We here show that dietary LA supplementation led to significant changes in biomarkers of oxidative stress and reduced kidney damage in diabetic apoE−/− mice.…”

Section: Introductionmentioning

confidence: 99%

α-Lipoic acid protects diabetic apolipoprotein E-deficient mice from nephropathy

Nickeleit

James

et al. 2011

Journal of Diabetes and its Complications

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Aim Both hyperglycemia and hyperlipidemia increase oxidative stress, and contribute to the development of diabetic nephropathy (DN). We investigated effects of α-lipoic acid, a natural antioxidant and a cofactor in the multienzyme complexes, on the development of DN in diabetic apolipoprotein E-deficient mice. Methods Twelve-weeks-old male apoE−/− mice on C57BL/6J genetic background were made diabetic with injections of streptozotocin (STZ). STZ-treated diabetic apoE−/− mice and non-diabetic control were fed with a synthetic high fat (HF) diet with or without LA supplementation. Multiple parameters including plasma glucose, cholesterol, oxidative stress markers, cytokines, and kidney cortex gene expression, and glomerular morphology were evaluated. Results LA supplementation markedly protected the beta cells and reduced cholesterol levels, attenuated albuminuria and glomerular mesangial expansion in the diabetic mice. Reno-protection by LA was equally effective regardless of whether the dietary supplementation was started 4 weeks before, simultaneously with, or 4 weeks after the induction of diabetes by STZ. LA supplementation significantly improved DN and oxidative stress in the diabetic mice. Severity of albuminuria was positively correlated with level of thiobarbituric acid reactive substances (TBARs) in the kidney (r2=0.62, P<0.05). Diabetes significantly changed the kidney expression of Rage, Sod2, Tgfb1 and Ctgf, Pdp2, nephrin and Lias. LA supplementation corrected these changes except that it further suppressed the expression of the Lias gene coding for lipoic acid synthase. Conclusions Our data indicate that LA supplementation effectively attenuates the development and progression of DN through its antioxidant effect as well as enhancing glucose oxidation.

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“…Chronic inflammatory diseases such as Crohn's disease and ulcerative colitis lead to a high risk of developing colorectal cancer (CRC) [1][2][3]. Other risk factors for the development of CRC include an unhealthy diet, smoking, analgesics and genetic factors [4,5]. Due to the asymptomatic nature of CRC, it is often diagnosed at the late stages when cancer has spread to other parts of the body [6,7].…”

Section: Introductionmentioning

confidence: 99%

Leukocyte populations and IL-6 in the tumor microenvironment of an orthotopic colorectal cancer model

Miller

Senior

Prakash

et al. 2016

ABBS

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Colorectal cancer (CRC) is a major health problem worldwide. It is often diagnosed late due to its asymptomatic nature. As with all cancers, an immune reaction is involved; however, in CRC, it is unknown if this immune response is favorable or unfavorable for disease progression. In this study, the immune response in mesenteric lymph nodes (MLNs) and Peyer's patches was investigated during development of CRC in an orthotopic mouse model. CRC was induced by injecting CT26 cells into the cecum wall of BALB/c mice. Flow cytometry was used to analyze leukocyte populations involved in tumor immunity in MLNs and Peyer's patches. Cryostat sections for immunohistochemistry were prepared from the caecum and colon from CRC-induced and sham-operated animals. Cytokines produced by mouse CT26 cell line were measured in vitro and in vivo. Significant increases in the number of CD8 + /TCR + and CD49b + /TCR − (natural killer) cells were found in MLNs and Peyer's patches in the CRC group. In addition, γδT cells were present in the lamina propria of the colon tissues from sham-operated mice, but absent in the colon tissues from mice with CRC. Immunohistochemical analysis of tumorous tissues showed eosinophil, CD69 + T cell, and CD11b + cell infiltration. Both in vitro and in vivo CT26 tumor cells were interleukin (IL)-6 positive. In addition, tumor-infiltrating CD45 + cells were also IL-6 positive. In summary, the kinetics of the immune response to CRC and the key effector lymphocytes that are implicated in tumor immunity are demonstrated. Furthermore, IL-6 is a key cytokine present within the tumor microenvironment.

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Western-Style Diets Induce Oxidative Stress and Dysregulate Immune Responses in the Colon in a Mouse Model of Sporadic Colon Cancer

Cited by 78 publications

References 36 publications

Proanthocyanidin Attenuation of Oxidative Stress and NF-κB Protects Apolipoprotein E-Deficient Mice against Diabetic Nephropathy

Proanthocyanidin Attenuation of Oxidative Stress and NF-κB Protects Apolipoprotein E-Deficient Mice against Diabetic Nephropathy

α-Lipoic acid protects diabetic apolipoprotein E-deficient mice from nephropathy

Leukocyte populations and IL-6 in the tumor microenvironment of an orthotopic colorectal cancer model

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