A relationship between cigarette smoke oxidants and atherosclerosis

Nutrition Health Review, Spring, 1993 by Caroll E. Cross

One of the primary steps in the development of atherosclerosis is the oxidation of low-density lipoprotein (LDL) in the blood by highly reactive molecules known as free radicals.

It has been shown that oxidized LDL is highly atherogenic. Cigarette smoke contains large quantities of free radicals, many of which are known to oxidize LDL.

The multiple layers of antioxidant defenses make it important to characterize the roles and effects of the various components making up that defense. This research sought to determine the effects of cigarette smoke on internally produced antioxidants -- such as dihydrolipoic acid (DHLA) and glutathione -- and externally supplied antioxidants (vitamin C), as assessed by the appearance of oxidized lipid and modified proteins.

Human plasma and human LDL were exposed in vitro to cigarette smoke in order to duplicate the effects of smoking on fluids in the lining of the respiratory tract, certain lung components, and plasma. When vitamin C, DHLA, and glutathione were added to plasma exposed to cigarette smoke, the following observations could be made:

1. Ascorbic acid protected the lipid, but not protein, components of plasma.

2. Gas-phase cigarette smoke (filtered to remove particulate matter) oxidized both plasma proteins and lipids, but whole cigarette smoke oxidized only the proteins.

3. Aldehydes, known to be present in cigarette smoke, damaged plasma proteins, but not lipids and did not deplete levels of vitamin C.

4. DHLA protected protein, preserved ascorbate levels, and provided partial protection against oxidation of lipids in plasma.

5. Glutathione protected only plasma proteins while having no effect on lipid oxidation.

6. Cigarette smoke is capable of making plasma LDL more oxidized than other substances that also act as oxidants.

These results suggest that the effect of cigarette smoke on the increased risk of atherosclerosis may not only be due to the direct oxidation of lipids and proteins; it may also have indirect effects, such as the depletion of various antioxidant defenses, which then allows other cellular processes (inflammation, for example) to modify LDL.