**5. Conclusion**

482 Lipoproteins – Role in Health and Diseases

PON, nmol/ mlmin

> 174 2\*

194 3\*,\*\*

> 173 3\*

189 2\*,\*\*

> 159 1\*

179 2\*,\*\*

> 223 6

> 215 3\*

> 221 4

> 255 3

> > 3

Ascorbic acid, mkmol/L

> 37.26 1.60\*,\*\*

> 41.79 0.44\*,\*\*

> 40.08 1.72\*,\*\*

> 54.30 0.97\*,\*\*

> > 35.46 1.10\*

48.59 0.96\*,\*\*

> 75.95 0.74\*

> 74.79 0.34\*

67.04 1.40

70.61 2.31

79.49 2.18\*

**Table 25.** The effect of grape polyphenol concentrates and grape wines on the plasma oxidant/antioxidant status in rats with the emotional-painful stress (in each group n=10).

Parameter

Isolated double bonds in ApоВ-LP

> 2.07 0.09\*

> 2.35 0.15\*

> 1.92 0.25\*

2.47 0.03\*,\*\*

> 1.52 0.06\*

> 2.21 0.07\*

> 5.43 0.12\*

> 5.55 0.15\*

4.83 0.11

5.39 0.04\*

5.75 0.17\*

Diene conjugates in ApоВ-LP

> 27.03 1.30\*,#

26.86 0.43\*

18.45 0.18\*,\*\*

14.50 0.35\*,\*\*

25.73 0.68\*,\*\*

27.68 0.60\*,\*\*

> 15.67 0.15\*

> 15.81 0.15\*

16.87 0.21

15.47 0.34\*

17.82 0.24


> 7.77 0.21\*

8.25 0.66\*,\*\*

8.91 0.29\*\*

10.42 0.16\*,\*\*

> 7.04 0.07\*

8.03 0.06\*,\*\*

> 10.03 1.72

11.52 0.24\*

9.49 0.24

9.97 0.16

10.22 0.36

Group

Str.+Con. Podarok Magaracha (AD)

Str.+Con. Krasen (АD)

Srt.+Wine Podarok Magaracha

Srt.+Wine Krasen

Str.+Con. Podarok Magaracha (DW)

Str.+Con. Krasen (DW)

Wine Podarok Magaracha

> Wine Krasen

Con. Podarok Magaracha (AD)

Con. Krasen (AD)

Ethanol <sup>236</sup>

The data presented as mean±SD \* - р0.05 versus intact animals \*\* - р0.05 versus stressed animals Based on our findings, it is possible to state that antioxidant complexes, particularly polyphenol extracts and the concentrates obtained from *Vitis Vinifera*, which are safe and reveal the potent antioxidant and stress-protective activity, should be used for reduction of proaterogenic states consequences in the complex prophylactic and treatment of atherosclerosis as effective stress-protective remedies.

Thus*,* administration of *Vitis Vinifera* substances can prevent the increase of the total lipoprotein and ApoB-LP content in the blood, and prevent the free radical process activation in the plasma lipoprotein particles, and, in general, normalize the lipid and lipoprotein metabolism in the liver in metabolic syndrome. These results have proven the ability of the investigated complexes to reduce such negative consequence of metabolic syndrome as development of atherosclerosis.

In addition, according to obtained research data the polyphenolic concentrates possess a potent protective activity both in acute and chronical neurogenic stress.

Our studies suggest that multicomponent active substances with antioxidant properties are more effective in correction of the proatherogenic states caused by stress and metabolic syndrome negative effects in comparison with individual antioxidants (particularly, αtocopherol). The research data suggest that the increased plasma antioxidant activity alone does not result in decreased foam cell formation, at least in the studied animal model. Moreover, *in vitro* studies have shown that α-tocopherol can be pro-oxidative rather than protective for lipids in isolated LDL. Similarly with vitamin E, vitamin C additives do not offer consistent benefit against atherosclerosis in animals.

The occurrence of tocopherol-mediated peroxidation and the mode of its prevention predicts that the balance of α-tocopherol and available coantioxidants, rather than αtocopherol alone, determines whether LDL lipid peroxidation occurs in biological systems. Inhibition of the free radical process with the polyphenolic complexes administration can be associated with their ability to increase the level of antioxidants – α-tocopherol, ascorbic acid and reduced glutathione in the test animal liver tissue compared with the group of the stressed animals. The complexes obtained from *Vitis Vinifera*, in particular, polyphenolic concentrates "Enoant" and "Polyphen", as well as grape wines (particularly "Cabernet") with their moderate use revealed the potent antioxidant activity. The preliminary results also suggest that coantioxidants inhibit lipoprotein lipid peroxidation *in vivo*. Thus, if LDL oxidation causes atherosclerosis, the requirement for coantioxidants may explain why supplementation with individual antioxidants, particular vitamin E alone, overall has yielded inconclusive results in the controlled human and animal intervention studies.

In conclusion, our research results may be used for the development of the atherosclerosis prophylaxis strategy, and treatment of diabetes mellitus and metabolic syndrome because recent studies proved insufficient effectiveness of α-tocopherol and advantages of multicomponent antioxidant complexes administration. The high effectiveness of the polyphenolic complexes obtained from *Vitis Vinifera,* including polyphenolic concentrates

"Enoant" (from grape of "Cabernet" grade) and "Polyphen" (from grape of "Rkatsiteli" grade) produced by the National Institute of Grape and Wine "Magarach" has been proven. Our results also confirmed the high effectiveness of the antioxidant complexes from grapes in the correction of the endothelial dysfunction, thus, including these extracts in the treatment schemes is very reasonable. As it would be expected from our observations, increasing the antioxidant oxidant defense by antioxidant supplementation has the ability to restore the endothelial vasomotor function.

An important question to be asked is whether the polyphenol antioxidants exerted their inhibitory effect on lesion progression only because of their antioxidant properties or, possibly, because of additional biological properties, in particular – the phytoestrogen activity.

However, further studies, especially in humans, are required to validate the role of these antioxidants in inhibiting LDL oxidation.

Nevertheless, there are some limitations in the use of the concentrates produced from red grade grapes because of the uric acid content changes.
