Dietary Approach to Attenuate Oxidative Stress

Dietary Approach to Attenuate Oxidative Stress, Hypertension, and Inflammation in the Cardiovascular System

Proceedings of the National Academy of Sciences of the United States of America

PNAS | May 4, 2004 | vol. 101 | no. 18 | 7094-7099

Medical Sciences

Lingyun Wu *, M. Hossein Noyan Ashraf *, Marina Facci *, Rui Wang(a), Phyllis G. Paterson(b) , Alison Ferrie(c) and Bernhard H. J. Juurlink*(d)

Departments of *Anatomy and Cell Biology and (a)Physiology, College of Medicine, and (b)College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E5; and (c)Plant Biotechnology Institute, National Research Council, Saskatoon, SK, Canada SW9 OW9


Imbalance between production and scavenging of superoxide anion results in hypertension by the inactivation of nitric oxide, and the increased oxidative stress from the resultant peroxynitrite that is produced promotes inflammatory processes such as atherosclerosis. Induction of phase 2 proteins promotes oxidant scavenging. We hypothesized that intake of dietary phase 2 protein inducers would ameliorate both hypertension and atherosclerotic changes in the spontaneously hypertensive stroke-prone rat. For 5 days/week for 14 weeks, we fed rats 200 mg/day of dried broccoli sprouts that contained glucoraphanin, which is metabolized into the phase 2 protein-inducer sulforaphane (Group A), sprouts in which most of the glucoraphanin was destroyed (Group B), or no sprouts (Group C). After 14 weeks of treatment, no significant differences were seen between rats in Groups B and C. Rats in Group A had significantly decreased oxidative stress in cardiovascular and kidney tissues, as shown by increased glutathione (GSH) content and decreased oxidized GSH, decreased protein nitrosylation, as well as increased GSH reductase and GSH peroxidase activities. Decreased oxidative stress correlated with better endothelial-dependent relaxation of the aorta and significantly lower (20 mm Hg) blood pressure. Tissues from Groups B and C had considerable numbers of infiltrating activated macrophages, indicative of inflammation, whereas animals in Group A had few detectable infiltrating macrophages. There is interest in dietary phase 2 protein inducers as means of reducing cancer incidence. We conclude that a diet containing phase 2 protein inducers also reduces the risk of developing cardiovascular problems of hypertension and atherosclerosis.

Abbreviations: CT, control diet; GPx, GSH peroxidase; GRed, GSH reductase; Grn, glucoraphanin; GS, glucosinolate; GSH, glutathione; GSSG, oxidized GSH; QR, quinone reductase; SD, Sprague-Dawley; SHR, spontaneously hypertensive rats; SHRsp, stroke-prone SHR.


Note from ISS:  Below is the press release regarding the above article.

Broccoli May Bolster Body's Defenses Against Heart Disease and Stroke

FOR IMMEDIATE RELEASE - May 3rd, 2004 2004-05-01-OTHER

University of Saskatchawan

May 03, 2004

Compounds in broccoli may supercharge the body's ability to mop up free radicals and so protect against high blood pressure, stroke and heart disease, according to research led by University of Saskatchewan health scientist Bernhard Juurlink and recently published in the Proceedings of the National Academy of Sciences (PNAS) in the U.S.

"Nearly all the studies to date have focused on the protective effects of these substances against cancer," said Juurlink, head of the U of S department of anatomy and cell biology. "This study is the first to show that broccoli sprouts rich in these compounds, through raising the antioxidant and thereby the anti-inflammatory capacities of cells, can correct major dysfunctions such as hypertension and stroke."

The research team is exploring oxidative stress which occurs when free radical production outstrips the body's ability to neutralize it. Free radicals are unstable chemical byproducts of the body's normal metabolism which damage essential cell molecules in a manner similar to the rusting of iron. This damage leads to cardiovascular disease and other ailments.

Tissues have a variety of defenses to prevent this "rusting" - systems that Juurlink and his team found can be bolstered by eating foods rich in chemicals called phase 2 protein inducers. One such inducer, glucoraphanin (Grn), is found in high levels in broccoli sprouts (baby broccoli plants with a pleasant, tangy flavor).

"Phase 2 inducers promote the production of phase 2 proteins," Juurlink says. "These proteins either promote scavenging of oxidants or decrease the chance of these oxidants being formed in the first place. The result is a huge multiplier effect. One phase 2 protein inducer likely has the same effect as thousands of typical anti-oxidant molecules."

The researchers fed broccoli sprouts to two groups of rats that were prone to high blood pressure and stroke. One group received sprouts high in Grn, while the other group received a Grn-poor variety. At the end of 14 weeks, the rats on the high-Grn diet displayed more vigorous antioxidant defense mechanisms. They also had lower blood pressure and decreased inflammation of the heart and kidney.

The study suggests a modest change in diet could have profound health benefits. Juurlink says if humans respond the same way as the test animals, one or two grams of fresh broccoli sprouts per day per kilo of body weight would do the trick. This works out to 70 to 140 grams (roughly two to four ounces) for a 70-kilogram person, or a smallish serving with supper every day. The team hopes to repeat the study in human subjects to confirm the beneficial effects.

Anti-cancer effects of the sprouts, documented in a study published in 2002 by a team at Johns Hopkins University School of Medicine in Maryland, appear to be due to the same enhanced antioxidant effect. The 2002 study also showed a powerful antibacterial effect against Helicobacter pylori, an organism known to cause stomach ulcers.

Why sprouts? They have much higher concentrations of Grn than mature broccoli. Juurlinkestimates you would need to eat 20 to 50 times as much of the mature plant to get the same benefits.

If broccoli sprouts are hard to come by in your supermarket, you can also get phase 2 protein inducers into your system with other foods. Some examples are flax seed, soy products, kale - and for dessert, raspberries, blackberries, strawberries, blueberries and cranberries.

Funding for the study was provided by the Saskatchewan Agricultural Development Fund. Other researchers on the team included Lily Wu (pharmacology), Hossein Noyan Ashraf (post-doctoral fellow in anatomy and cell biology), Marina Facci (graduate student), Rui Wang (physiology), Phylis Paterson (pharmacy and nutrition), and Alison Ferrie (National Research Council's Plant Biotechnology Institute).

For more information, contact:

Bernhard Juurlink
Department of Anatomy and Cell Biology
College of Medicine
University of Saskatchewan
(306) 966-4083

Michael Robin
Research Communications
University of Saskatchewan
Tel: (306) 966-2427