Free radicals, reactive oxygen species (ROS), and reactive nitrogen species (RNS) are implicated in numerous pathological conditions such as inflflammation, atherosclerosis, carcinogenesis, metabolic disorders, cellular aging and reperfusion damage (Ames et al., 1993). The oxidative damage to DNA in the formation of certain cancers and lipid oxidative damage in the occurrence and progression of vascular diseases are attributed to ROS (Rajendran et al., 2004). Smoking acts synergistically with other risk factors, substantially increasing the risk of congestive heart diseases and thus smoking nearly doubles the risk of ischemic stroke (Shinton and Beevers, 1989). The cell possesses a natural antioxidant defense mechanism that enables it to scavenge the free radicals. However, when the free radicals outweigh the defense mechanism, the resulting effect is oxidative stress. Intake of natural antioxidants may help to maintain an adequate antioxidant defense status

(Halliwell et al., 1995). In the present study, the objective was to evaluate the effects of EOE, which is a well established antioxidant,on cardio-respiratory and anti-oxidant status of volunteers with a

long smoking history. The study was conducted in two groups – one treated with 250mg BID of EOE and the other with a placebo. Eligibility was based on being aged between 20 and 60 years, excessive (>15 cigarettes/day) and long smoking history (>10 years). Subjective parameters associated with smokers and the objective parameters were evaluated. EOE showed improvement in smoking related subjective parameters such as shortness of breath on exertion, mouth hygiene,

cough with expectoration, heart burn, sleep deprivation and tiredness when compared to baseline values. It is well known that when the level of LDLs is high, they accumulate in the artery wall, which leads to the development and progression of atherosclerosis. HDLs counter atheroscle

rosis directly by removing cholesterol from foam cells and inhibiting the oxidation of LDLs (Barter et al., 2007). HDL level had signifificantly increased after 60 days in the EOE treated group whereas there was no signifificant difference with the placebo group. Total cholesterol is one of the direct biochemical parameters to evaluate cardiovascular complications. Both TC/HDL and LDL/HDL ratios, designated as cardiac risk ratios, showed signifificant (p < 0.001) improvement after two months of treatment with EOE. Platelets play a signifificant role in cardiovascular disease. In particular, platelet hyperaggregability is also associated with the risk factors for coronary artery disease (e.g. smoking, hypertension and hypercholesterolemia) (Willoughby et al., 2002). Platelet aggregation was signifificantly (p < 0.001) inhibited after two months of treatment with EOE. Lipoprotein (a), a putative risk factor for atherosclerotic diseases, also decreased signifificantly. The above findings indicated a beneficial effect on the cardiovascular system of the recipients of

EOE. EOE treatment for 60 days signifificantly decreased 8-OH-2-deoxyguanosine levels, which indicated attenuation of the oxidative stress induced accelerated breakdown of DNA in the

body. EOE treatment for 60 days signifificantly decreased the mitotic index and normalized the chromosomal aberration. Placebo treatment did not have any potent effect on mitotic index and chromosomal aberration. Treatment with EOE showed no improvementin respiratory fitness of the subjects, but there was no adverse effect of EOE treatment on lung function. The observed forced expiratory volume, which was 80% of forced vital capacity, in the smoking volunteers, substantiates the fifindings regarding the maintenance of respiratory fifitness. The patients did not complain of

any adverse effects of EOE treatment. It is important to note that in the present pilot study, it

was not stipulated that subjects restrict their smoking habits; hence the improvement in subjective and biochemical parameters were considered to be mainly due to the treatment. A longer period of EOE treatment might exhibit further improvement in the tested parameters.