Does Resveratrol Protect Against Second-Hand Smoke Exposure?

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It has been well documented that resveratrol, a polyphenolic compound that is found in the skins and seeds of red grapes, functions as an antioxidant, an anti-inflammatory agent, and an anti-carcinogen.¬† The ‚ÄúFrench Paradox‚ÄĚ describes the phenomenon that French nationals, who drink significantly more red wine that others throughout the world, have lower mortality from heart disease, despite higher frequency of cigarette smoking.¬† It is the resveratrol in red wine that is often credited with this lower frequency of heart disease.¬† Some studies have shown that resveratrol reduces cigarette smoke-induced oxidative stress, decreases negative alterations of endothelial cell structures, and prevents acute endothelial dysfunction in otherwise healthy smokers.¬† However, other studies have found just the opposite, in that resveratrol does not protect against cigarette smoke-induced problems.¬†

As a result of the contrasting evidence for or against resveratrols’ role as a protector against cigarette smoke-induced ailments, the authors of the study presented today (published in April of 2011) chose to confirm whether or not resveratrol would protect against cigarette smoke-induced cardiovascular effects, and also whether other problems caused by cigarette smoke inhalation are alleviated by the protective effects of resveratrol.

Out of all of the negative health effects caused by smoking cigarettes, the most prominent are cardiovascular and respiratory effects such as atherosclerosis, coronary artery disease, asthma, and COPD (chronic obstructive pulmonary disease).  Second-hand smoke exposure is also associated with an increased risk for all of the aforementioned health effects.  The major cause of many of the adverse health effects caused by cigarette smoking or second-hand smoke exposure is oxidative stress.  Cigarette smoking and second-hand smoke exposure is also highly linked to lung inflammation, increased risk of developing heart disease, emphysema, increased oxidative stress, and impairment of endothelial function.

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In order to determine if resveratrol has any protective effects on both cardiovascular and respiratory function in smokers, or those exposed to second-hand smoke, the authors of the study presented today exposed second-hand smoke to juvenile pigs, a study organism which is often used in lieu of human participants, due to similar physiological responses.

Methods

Juvenile pigs were randomly assigned to four different treatments, with four pigs per treatment: sham (control), resveratrol alone, second-hand smoke, or second-hand smoke plus resveratrol. 

In order to achieve the second-hand smoke exposure, a single cigarette manual smoking machine was used, which was adjusted to a rate of 3 puffs per minute with 57mL per puff with total duration of 2 seconds.  The second-hand smoke was pumped in with unfiltered indoor air, into a chamber housing the unsedated and unrestrained pigs.  A total of 12 cigarettes were burned over 1 hour every day for 14 days.  Those pigs in the sham (control) treatment were placed in the same chambers as the other treatment pigs, however an unlit cigarette was installed on the smoking machine, instead of one that was lit.  Those pigs in the resveratrol treatments were force-fed resveratrol gelatin capsules (5mg/kg) for 14 days.  Carbon monoxide, oxygen, and carbon dioxide levels inside the chamber were measured.

The following physiological characteristics were measured for each of the pigs (methods of which I will not describe here, since some are relatively graphic): flow-mediated dilation (FMD), left ventricle end-systolic volume, end-diastolic volume, ventricle volume (calculation), ejection fraction (EF, calculation), blood pressure (systolic, diastolic, mean arterial, and pulse), blood gas levels (oxygenated hemoglobin, carboxy-hemoglobin, methemoglobin, total hemoglobin), plasma nitrate/nitrite, cotinine, nitrotyrosine, C-reactive peptide, ethoxyresorufin-o-deethylase (EROD) activity, broncoalveolar lavage (BAL) fluid differential, total cell count, and finally, leukocyte elastase activity.  Histology was also done on the heart, lung, liver, aorta, and the coronary and brachial arteries (at the end of the experiment).

Results

Chamber conditions, flow-mediated dilation (FMD), left ventricle end-systolic volume, end-diastolic volume, ventricle volume, ejection fraction, blood pressure, and blood gas levels.

  • ¬† ¬† ¬† Chamber levels of CO and particulate matter were higher in second-hand smoke exposure than control exposures.
  • ¬† ¬† ¬† Chamber levels of O2 decreased with second-hand smoke exposure.
  • ¬† ¬† ¬† Chamber levels of CO2 were below the detection limit for all treatments.
  • ¬† ¬† ¬† Serum cotinine levels were significantly higher in second-hand smoke exposed pigs (both with and without resveratrol) than the sham controls.
  • ¬† ¬† ¬†¬†¬†There was a significant decrease in flow-mediated dilation (FMD) in second-hand smoke exposed pigs (even more so after 7 days of treatment).

o   Resveratrol had no effect on FMD in any of the treatments.

  • ¬† ¬† ¬† Second-hand smoke exposure did not significantly alter left ventricle end-systolic volume, end-diastolic volume, or ejection fraction, even after the 14 days were completed.

o   Resveratrol significantly preserved the left ventricle ejection fraction in second-hand smoke exposed pigs.

o   Resveratrol significantly preserved left ventricle end-diastolic volume in second-hand smoke exposed pigs.

o   Left ventricle end-systolic volume was not affected by resveratrol (or second-hand smoke exposure) treatment.

  • ¬† ¬† ¬† No significant differences were found in heart weight, body weight, or the heart weight/body weight ratios in any of the treatment groups.
  • ¬† ¬† ¬† Blood pressure was not significantly altered by any treatment groups.
  • ¬† ¬† ¬† Second-hand smoke exposure and the resveratrol treatment caused a significant decrease in methemoglobin, with the second-hand smoke exposure plus resveratrol showing the greatest decrease.

o   Neither second-hand smoke exposure nor resveratrol treatment had any effect on the remaining blood gases measured.

Plasma nitrate/nitrite, cotinine, nitrotyrosine, C-reactive peptide, and ethoxyresorufin-o-deethylase (EROD) activity.

  • ¬† ¬† ¬† Serum nitrate/nitrite levels showed no significant changes over time with any treatment group.
  • ¬† ¬† ¬†¬†¬†Second-hand smoke exposure caused a significant increase in serum nitrotyrosine levels.

o   Resveratrol had no effect on nitrotyrosine levels in any treatment group.

  • ¬† ¬† ¬† Second-hand smoke exposure caused a significant increase in serum C-reactive peptide levels.

o   Resveratrol had no effect on serum C-reactive peptide levels in any treatment group.

  • ¬† ¬† ¬† Second-hand smoke exposure caused a significant increase in lung EROD activity.

o   Resveratrol had no effect on lung EROD activity in any treatment group.

Broncoalveolar lavage (BAL) fluid differential, total cell count, leukocyte elastase activity, and histology.

  • ¬† ¬† ¬†¬†¬†Total white blood cell count was significantly increased after 14 days of second-hand smoke exposure, compared to the sham control.

o   Resveratrol had no effect on white blood cell count in any treatment group.

  • ¬† ¬† ¬† Histology showed that there was an increase in intra-alveolar macrophages in second-hand smoke exposed pigs than the sham controls, both in the presence and absence of resveratrol.
  • ¬† ¬† ¬† There was no histological evidence of emphysema in any treatment group.
  • ¬† ¬† ¬† There was a significant increase in BAL fluid leukocyte elastase activity after second-hand smoke exposure.

o   Resveratrol had no effect on elastase activity.

  • ¬† ¬† ¬† There were no differences in arterial wall thickness or arterial diameter in the aorta, brachial artery, or coronary artery in any treatment group.

What do all these results mean?

The authors of this study stress that the most important finding of this study is that second-hand smoke exposure resulted in a decrease in flow-mediated dilation by 7 days into the treatment.  Resveratrol successfully attempted to combat this harm by increasing end-diastolic volume, however, had no effect on the flow-mediated dilation impairment by second-hand smoke exposure. 

The results of this study showed that second-hand smoke exposure caused pulmonary inflammation, systemic inflammation, increased oxidative stress, and increased biological inactivation of nitric oxide, all of which are known to be causative factors in endothelial dysfunction.  Since resveratrol did nothing to counteract the inflammatory and oxidative stress caused by second-hand smoke exposure, the small cardiovascular benefit it did provide must have been a result of a mechanism different from the usual anti-inflammatory or antioxidative mechanisms that resveratrol is often most known to function.  This unknown mechanism requires further study.

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Under normal conditions, it has often been shown that resveratrol acts as a strong anti-inflammatory agent, and also a strong antioxidant.  However, it appears that under the conditions of second-hand smoke exposure, these effects are no longer seen.  Some studies have shown that when taken in very high doses, resveratrol can be a pro-oxidant and promote atherosclerosis.  The lack of anti-inflammatory and antioxidant effects of the resveratrol in this study could potentially be a result of the dosage used on the pigs.  At 5mg/kg (the dose given to the pigs in this study), this dose of resveratrol is several times higher than what is recommended by the manufacturer.  It is possible that this lack of a protective effect of resveratrol on the pigs exposed to second-hand smoke in this study is because the dose was simply too high, and thus created a negative rather than protective effect of the agent.

In summary, though resveratrol did protect again one element of cardiovascular disease, it did not protect against anything else (both cardiovascular and pulmonary).  Since there is a decent chance that the dose of resveratrol was too high, more studies need to be completed where different doses of resveratrol are given, in order to determine if there is an optimal dose for resveratrol protection again second-hand smoke-induced health risks, or if resveratrol will never protect against these diseases.

I’d love to hear what you all think!  Please feel free to comment below!

Source: doi:10.1016/j.fct.2011.04.005.

I am not a health professional, nor do I pretend to be. Please consult your doctor before altering your alcohol consumption habits. Do not consume alcohol if you are under the age of 21. Do not drink and drive. Enjoy responsibly!

1 comment for “Does Resveratrol Protect Against Second-Hand Smoke Exposure?

  1. Brent
    December 26, 2011 at 6:17 am

    Second hand smokers seem to be more susceptible to diseases since they are the ones who directly inhales the smoke coming from the cigarettes. I hope that more studies must be conducted to prove that this element called Resveratrol helps second hand smokers free themselves from cardiopulmonary disease.

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