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20171
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Subject: Veterinary Pathology × Author: SRINIVASA NAIK, H × Start date: 2010 × Type: Thesis × Thesis Type: Ph.D ×
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    ThesisItemOpen Access
    MOLECULAR AND PATHOLOGICAL STUDIES OF INDUCED HYPERLIPIDEMIA AND ATHEROSCLEROSIS IN RATS AND ITS AMELIORATION WITH FLAXSEEDS (LINUM USITATISSIUMUM) AND GREEN TEA (CAMELLIA SINENSIS)
    (SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2017-05) SRINIVASA NAIK, H; SRILATHA, Ch(MAJOR); SUJATHA, K; SREEDEVI, B; PRASAD, T.N.V.K.V
      ABSTRACT : Hyerlipidemia is the disorder of lipid metabolism, characterized by elevated serum total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C) and very low density lipoproteins cholesterol (VLDL-C) and decreased high density lipoprotein cholesterol (HDL-C). Atherosclerosis is diverse disease with heterogenous mechanisms of progression and is an oxidative, chronic inflammatory and thrombotic disease referring to fatty deposits on the inner lining of the large to medium sized elastic and muscular arteries and is precipitated by elevated level of low density lipoprotein cholesterol (LDL-C) in the blood. Atherosclerosis associated coronary heart disease is the second largest cause of mortality worldwide in humans. Current reports suggest that by the year 2020, India will have the largest cardio vascular disease (CVD) burden in the world. Realizing the importance of ethno medical practices, flaxseed and green tea supplementation along with atherogenic diet has been taken to combat the hyperlipidemia associated atherosclerosis. Flaxseed (Linumusitatissiumum) has been identified as a significant alternative source of omega 3 fatty acids and alpha linoleic acid (ALA). Therapeutic activities of flaxseed is well proven, one of them is anti-atherosclerotic due to its lipid lowering activity which is mainly attributed to its Secoisoarciresinol diglucoside (SDG). Green tea (Camellia sinensis) polyphenols known to have various medical health beneficial effects like anti-inflammatory, anti-oxidative, anti-arthritic, anti angiogenic, anti-metastatic, anti-cancer, anti-obesity, anti hyperlipidemic, anti-atherosclerotic, neuroprotective, anti-dental caries and antimicrobial (bacterial, viral & fungal) properties in human, animal and in vitro studies. So the present study was designed with a view to study molecular aspects of hyperlipidemia associated atherosclerosis in male Wistar albino rats and an attempt was made to identify various molecular preventive effects of flax seeds (Linumusitatissiumum) and green tea (Cameliasinensis). The present study was carried out by procuring 72 wistar albino rats, that were randomly divided into six groups consisting of 12 rats in each group. Hyperlipidemia associated atherosclerosis was induced by atherogenic diet consisting of 1% cholesterol and 15% saturated oil added to the 1000g of standard rat diet and given to group II rats. Flaxseed @ 7.5g/kg/day and green tea @ 100mg/kg/day gavaged orally to group V and VI rats for 90 days along with atherogenic diet. Group I kept as control and given standard rat diet, group III as flaxseed control and given 7.5g/kg/day of flaxseed along with standard rat diet, whereas group IV kept as green tea control and given 100mg/kg/day/Po along with standard rat diet for 90 days. Six rats from each group were sacrificed 45 days apart each. Atherogenic diet fed group (Group II) rats clinically showed obesity with significant increase (p<0.05) in the body weight. Rats were sluggish with poor hair coat. Green tea supplementation (Group VI) significantly reduced the obesity and body weight compared to moderate reduction of obesity and body weight in flaxseed ameliorated group (Group V). Whereas green tea control group (Group IV) rats were apparently healthy, slim with shiny hair coat. Total leukocyte count (TLC), total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C) were significantly (p<0.05) higher, whereas high density lipoprotein cholesterol (HDL-C) was significantly reduced in group II. Oxidative damage indicators like catalase, SOD, GPx, reduced glutathione and glutathione S transferase were significantly (p < 0.05) reduced, whereas lipid peroxidation products of TBARS level was non-significantly (p < 0.05) increased in liver and heart tissues of atherogenic diet fed group (Group II). Flaxseeds supplementation (Group V) reduced the hyperlipidemia certain extent caused by atherogenic diet by reducing the modest level of TC, TG, LDL-C and mild elevation of HDL-C. Flaxseeds non-significantly (p < 0.05) increased the cellular anti-oxidant enzymes and modestly reduced the level of TBARS. Whereas green tea (Group VI) supplementation effectively controlled the hyperlipidemia by reducing all the serum total cholesterol, triglycerides, low density lipoprotein cholesterol and very low density lipoprotein cholesterol and enhanced the good high density cholesterol and significantly (p < 0.05) enhanced all the tissue anti-oxidant enzymes and modestly reduced the TBARS levels. Microscopically hepatic steatosis was prominent in atherogenic diet fed group (Group II). Complete absence of fatty change was evident in green tea treated group (Group VI) compared to flaxseed group (Group V). Histopathologically, endothelial degeneration, sub intimal fat cells, foam cells with attached microthrombi was observed in majority of the cases in group II rats aorta fed on atherogenic diet. All these changes were also evidenced by ultrastructural studies. Mild endothelial degeneration was evident in flaxseed ameliorated group. Majority of the changes of initiated atherosclerosis were minimized by green tea supplementation. No such lesions were seen in control, flaxseed and green tea alone fed control groups (Group I, III & IV) throughout the study period. Mild endothelial cell proliferation with formation of vascular channels in between cardiac muscle fibers, liver and in kidney was observed throughout the study period of flaxseed fed group (Group III) rats. VEGF positivity was observed in endothelial cells, thrombus and structurally modified stromal cells of initiated atherosclerotic lesion. Initiated atheromatous plaque showed high level of positivity with Bax compared with other parts of blood vessel. On the other hand, selective moderate to severe positivity with CD 31, CD44, E cadherin and Beta catenin was observed in the initiated atherosclerotic lesion characterized by endothelial degeneration, sub endothelial lipid laden macrophages, and endothelial adhered thrombus and erythrocytes. Various levels of positivity with above markers was also observed in flaxseed and green tea ameliorated groups based on the initiated atherosclerotic lesion in these groups. Present study revealed positive expression of proinflammatory cytokine TNF alpha by RT-PCR (Real time PCR) in atherogenic diet fed group aorta (Group II) compared to standard diet fed rats (Group I). Flaxseed and green tea ameliorated groups (Group V and VI) showed significant reduction in the expression of TNF alpha in contrary to atherogenic diet fed group (Group II). IL-18 expression was not noticed in any groups of the present study. In conclusion atherogenic diet of present study established the hyperlipidemia and initiated the atherosclerosis in the aorta evidenced by histopathology and molecular expression of PECAM-I (CD 31), CD44, E cadherin and Beta catenin and tissue TNF alpha. Flaxseeds supplementation reduced the hyperlipidemia associated atherosclerosis to certain extent, but not completely ameliorated the changes. On the other hand, green tea supplementation effectively controlled the hyperlipidemia associated atherosclerosis and enhanced all the tissue anti-oxidant enzymes.