Single article

Fufaeva Alena I., Kozlov Vadim A., Sapozhnikov Sergey P.

Cellular Response to Alcohol in the Conditions of Amyloidosis Model Formation

Keywords: 10 ethyl alcohol, dry red wine, sucrose, fructose, amyloidosis modeling, liver, kidney, spleen, mice

There is evidence that dry red wine Cabernet Sauvignon prevents the development of Alzheimer's disease and improves the condition of patients. The effect is allegedly related to the influence of wine resveratrol on the system of sirtuins. However, acetaldehyde, which is formed from ethanol, is a highly reactive molecule that can bind to almost any organic substance. Therefore, it makes sense to investigate the way weak 10 ethyl alcohol and such an active glycating agent as fructose affect the formation of experimental amyloidosis. The aim of the study is to differentiate the direct influence of ethyl alcohol on amyloidosis formation in the experiment from the influence of organic substances of dry red wine. The experiment was performed on 55 white mongrel male mice aged 30 days weighing 25±5.2 g. The mice were divided into six groups. Five mice made an intact group (1st). The rest underwent simulation of systemic amyloidosis by subcutaneous administration of 10% aqueous solution of dry dairy cream substitute during 30 days once a day every other day. Ten mice served as the control of the model formation (2nd group); as well as intact mice, they had free access to water and food. Against the background of systemic amyloidosis formation groups of ten mice in the free access mode, instead of water, four groups received: group 3 –10 ethyl alcohol with 5% sucrose; group 4 – 10 ethyl alcohol with 5% fructose; group 5 – dry red wine Cabernet Sauvignon; group 6 – dry red wine Cabernet Sauvignon with 5% fructose. Fructose was used as a glycating agent, which is more active than glucose. In 30 days, the mice were decapitated; the organs (liver, kidney, spleen) were weighed and embedded in paraffin. Paraffin sections of organs of 5 microns in thickness were stained with hematoxylin and Congo red according to H. H. Bennhold and microscoped in transmitted light. The number of hepatocytes, tubular epithelial cells, glomeruli, erythroid islet cells, and lymphocytes was calculated in the preparations. Differences in the mean values in groups were evaluated using the chi-squared test 2. Simulation of systemic amyloidosis, as was expected, was accompanied by a cytotoxic effect. The number of hepatocytes decreased by 17% (p = 0,001), tubular epithelial cells – by 11% (p = 0,0017), tubular epithelium with apical damage – by 23% (p = 0,0024), glomeruli – by 6,5% (p = 0,706), erythroid islet cells – by 8% (p = 0,047), lymphocytes – by 10% (p = 0,281). 10 ethyl alcohol with 5% sucrose had a pronounced proliferative effect: the number of hepatocytes increased twice (p = 0,0000), tubular epithelial cells – by 93% (p = 0,0000), and erythroid islet cells – by 32% (p = 0,0000). But the number of renal glomeruli decreased by 48% (p = 0,0001), and the lymphocytes almost disappeared – a tenfold decrease (p = 0,0000). The addition of 5% fructose to ethyl alcohol completely blocked the proliferative effect, except for erythroid islet cells, the number of which increased by 3,26 times (p = 0,0000). Dry red wine practically did not change the cellular composition of the organs under study, and adding 5% fructose to it was accompanied by a cytotoxic effect comparable to the control group of the model. Thus, 10 ethyl alcohol effectively reduces the severity of amyloid damage in the experiment both on the tissue and the cellular level; 10 ethyl alcohol is a more effective means of preventing amyloid damage than red dry wine Cabernet Sauvignon; fructose blocks the protective effects of ethyl alcohol and red dry wine Cabernet Sauvignon.

References

  1. KozlovA., Golenkov A.V., Sapozhnikov S.P. Minornye primesi potreblyaemogo alkogolya kak prichina smertnosti naseleniya [Minor admixtures of consumed alcohol as a cause of population mortality]. Narkologiya, 2013, vol. 12, no. 9(141), pp. 66–70.
  2. KozlovA., Sapozhnikov S.P., Karyshev P.B., Sheptukhina A.I., Nikolaeva O.V. Model’ sistemnogo amiloidoza u molodykh myshei [Model of systemic amyloidosis in young mice]. Byulleten eksperimentalnoi biologii i meditsiny, 2016, vol. 162, no 10, pp. 523–527.
  3. KozlovA., Sapozhnikov S.P., Sheptukhina A.I., Golenkov A.V. Parametabolizm kak nespetsificheskii modifikator supramolekulyarnykh vzaimodeistvii v zhivykh sistemakh [Parametabolism as a non-specific modifier of supramolecular interactions in living systems]. Vestnik Rossiiskoi akademii meditsinskikh nauk, 2015, vol. 70, no 4, pp. 397–402.
  4. FufaevaI., Aleksandrova V.Yu., Vasil’eva Yu.V. Vliyanie desyatiprotsentnogo etilovogo spirta i krasnogo vinogradnogo vina na formirovanie amiloidoza v eksperimente [Influence of ten percent ethyl alcohol and red grape wine on the formation of amyloidosis in the experiment]. In: Sbornik nauchnykh trudov molodykh uchenykh i spetsialistov: v 2 ch. [Young scientists and specialists scientific papers collection. 2 parts]. Cheboksary, Chuvash State University Publ., 2019, part 2, pp. 325–329.
  5. FufaevaI., Kozlov V.A., Sapozhnikov S.P., Petrova Yu.V., Aleksandrova V.Yu. Vliyanie krasnogo vinogradnogo vina i ego sochetaniya s geksozami na formirovanie standartnoi modeli amiloidnoi bolezni [Influence of red grape wine and its combination with hexoses on the formation of the standard model of amyloid disease]. Acta Medica Eurasica, 2018, no 1, pp. 42–51. Available at: http://acta-medica-eurasica.ru/single/2018/1/6.
  6. Ahmed N., Babaei-Jadidi R., Howell S.K., Beisswenger P.J., Thornalley P.J. Degradation products of proteins damaged by glycation, oxidation and nitration in clinical type 1 diabetes. Diabetologia, 2005, vol. 48, no. 8, pp. 1590–1603. DOI: https://doi.org/10.1007/s00125-005-1810-7.
  7. Babaei-Jadidi R., Karachalias N., Ahmed N., Battah S., Thornalley P.J. Prevention of incipient diabetic nephropathy by high dose thiamine and benfotiamine. Diabetes, 2003, vol. 52, no. 8, pp. 2110–2120. DOI: https://doi.org/10.2337/diabetes.52.8.2110.
  8. Drygalski K., Fereniec E., Koryciński K., Chomentowski A., Kiełczewska A., Odrzygóźdź C., Modzelewska B. Resveratrol and Alzheimer’s disease. From molecular pathophysiology to clinical trials. Gerontol., 2018, vol. 113, pp. 36–47. DOI: https://doi.org/10.1016/j.exger.2018.09.019.
  9. Gomes B.A.Q., Silva J.P.B., Romeiro C.F.R., Dos Santos S.M., Rodrigues C.A., Gonçalves P.R., Sakai J.T., Mendes P.F.S., Varela E.L.P., Monteiro M.C. Neuroprotective Mechanisms of Resveratrol in Alzheimer’s Disease: Role of SIRT1. Oxid Med Cell Longev, 2018, Article ID 8152373, 15 p. DOI: https://doi.org/10.1155/2018/8152373.
  10. Hayden E.Y., Yamin G., Beroukhim S., Chen B., Kibalchenko M., Jiang L., Ho L., Wang J., Pasinetti G.M., Teplow D.B. Inhibiting amyloid β-protein assembly: Size-activity relationships among grape seed-derived polyphenols. Neurochem, 2015, vol. 135, no. 2, pp. 416–430. DOI: https://doi.org/10.1111/jnc.13270.
  11. Ho L., Chen L.H., Wang J., Zhao W., Talcott S.T., Ono K., Teplow D., Humala N., Cheng A., Percival S.S., Ferruzzi M., Janle E., Dickstein D.L., Pasinetti G.M. Heterogeneity in red wine polyphenolic contents differentially influences Alzheimer’s disease-type neuropathology and cognitive deterioration. Alzheimers Dis., 2009, vol. 16, no. 1, pp. 59–72. DOI: https://doi.org/10.3233/JAD-2009-0916.
  12. Ko S.Y., Ko H.A., Chu K.H., Shieh T.M., Chi T.C., Chen H.I., Chang W.C., Chang S.S. The Possible Mechanism of Advanced Glycation End Products (AGEs) for Alzheimer’s Disease. PLoS One, 2015, vol. 20, no. 10(11):e0143345. DOI: https://doi.org/10.1371/journal.pone.0143345.
  13. Ono K., Condron M.M., Ho L., Wang J., Zhao W., Pasinetti G.M., Teplow D.B. Effects of grape seed-derived polyphenols on amyloid beta-protein self-assembly and cytotoxicity. Biol. Chem., 2008, vol. 283, no. 47, pp. 32176–32187. DOI: https://doi.org/10.1074/jbc.M806154200.
  14. Pastor M.T., Kümmerer N., Schubert V., Esteras-Chopo A., Dotti C.G., López de la Paz M., Serrano L. Amyloid toxicity is independent of polypeptide sequence, length and chirality. Mol. Biol., 2008, vol. 375, no. 3, pp. 695–707. DOI: https://doi.org/10.1016/j.jmb.2007.08.012.
  15. Sawda C., Moussa C., Turner R.S. Resveratrol for Alzheimer’s disease. N.Y. Acad. Sci., 2017, vol. 1403, no. 1, pp. 142–149. DOI: https://doi.org/10.1111/nyas.13431.
  16. Sharman A., Jumadilovper J., eds. The scientific basis for healthy aging and antiaging processes. New York, Mary Ann Liebert, Inc., 2011, 184 p.

About authors

Fufaeva Alena I.
Post-Graduate Student of Biology and Microbiology Department, Chuvash State University, Russia, Cheboksary (priffetik@bk.ru)
Kozlov Vadim A.
Doctor of Biological Sciences, Professor of Department Medical Biology with a Course in Microbiology and Virology, Chuvash State University, Russia, Cheboksary (pooh12@yandex.ru)
Sapozhnikov Sergey P.
Doctor of Medical Sciences, Professor, Head of Department Medical Biology with a Course in Microbiology and Virology, Chuvash State University, Russia, Cheboksary (adaptogon@mail.ru)

Article link

Fufaeva Alena I., Kozlov Vadim A., Sapozhnikov Sergey P. Cellular Response to Alcohol in the Conditions of Amyloidosis Model Formation [Electronic resource] // Acta medica Eurasica. – 2020. – №1. P. 29-36. – URL: http://acta-medica-eurasica.ru/en/single/2020/1/4/.