(PTFS08-05-26) Temporal Antioxidant Enzyme Alterations in the Distal Colon During Angiotensin II-Induced Hypertension: Modulation by a Mixed-Berry Diet

Objectives: Angiotensin (Ang) II-induced hypertension (HTN) is associated with intestinal oxidative stress and barrier dysfunction. Dietary polyphenols, including those abundant in mixed berries, have demonstrated anti-hypertensive and antioxidant properties. This study examined the temporal alterations of antioxidant and pro-oxidant enzyme expression in the distal colon and whether a mixed-berry (MB) diet modulates their expression during Ang II HTN.

Methods: Male Sprague-Dawley rats were fed an AIN-93M diet (Control [CON], Ang, Losartan [LOS; 20 mg/kg BW]) or an energy and macronutrient-matched AIN-93M diet supplemented with 10% w/w freeze-dried MB (equal parts blackberry, blueberry, raspberry, strawberry) for 8 weeks. Ang II (270 ng/kg BW/min; Ang, LOS, MB) or saline (CON) was delivered via osmotic minipump starting at week 4. Distal colon tissue was collected at weeks 4 (baseline, before minipumps), 6, and 8. Protein expression of antioxidant enzymes (NAD(P)H quinone oxioreductase [NQO]1, catalase [CAT], superoxide dismutase [SOD]1, SOD2, SOD3, glutathione peroxidase [GPx]3), pro-oxidant markers (NADPH oxidase [NOX]1, NOX2), and renin-angiotensin system (RAS) components (Ang type 2 receptor [AT2R], Ang-converting enzyme [ACE]2) were assessed by Western blot. Data were analyzed by one-way ANOVA with Tukey's post-hoc test; n = 5–8 per group.

Results: At week 4, SOD3 (p = 0.01) and AT2R (p = 0.02) were significantly higher in MB vs. CON, while GPx3 (p = 0.02) was lower in MB. At week 6, ACE2 was higher in MB vs. Ang (p < 0.01). By week 8, SOD1 was significantly lower in Ang (p = 0.01) and LOS (p < 0.01) vs. CON, while MB was not different from CON. MB showed elevated SOD2 vs. CON (p = 0.04) and Ang (p = 0.05) and higher CAT vs. all groups (p < 0.05), while NQO1 trended higher vs. Ang (p = 0.08). NOX1 was lower in LOS vs. CON (p = 0.04) and MB (p = 0.01).

Conclusions: A MB diet was associated with early engagement of the counter-regulatory RAS axis in the distal colon, temporally preceding a coordinated upregulation of antioxidant enzyme expression at week 8. These findings suggest that berry polyphenols may modulate colonic redox adaptation during Ang II-induced HTN through RAS-redox crosstalk.

Funding Sources: The Agriculture and Food Research Initiative from the USDA National Institute of Food and Agriculture.