TY - JOUR
T1 - Oxidative renal injury and lipoprotein oxidation in hypercholesterolemic atherogenesis
T2 - Role of eicosapentaenoate-lipoate (EPA-LA) derivative
AU - Kumar, Sekar Ashok
AU - Sudhahar, Varatharajan
AU - Varalakshmi, Palaninathan
N1 - Funding Information:
The first author gratefully acknowledges the financial assistance in the form of Senior Research Fellowship by the Council of Scientific and Industrial Research (CSIR), New Delhi, India.
PY - 2006/7
Y1 - 2006/7
N2 - Hypercholesterolemia, an independent risk factor for increased oxidative renal injury, is associated with the formation of oxidized low-density lipoprotein. Production of reactive oxygen species and nitrogen species have been implicated in diet-induced hypercholesterolemia, principally as means of oxidising low-density lipoproteins. This inturn initiates the accumulation of cholesterol in macrophages, which sets key event in the initiation of atherosclerosis. The aim of the present work is to evaluate the effects of eicosapentaenoic acid (EPA), DL α-lipoic acid (LA) and eicosapentaenoate-lipoate derivative (EPA-LA) in controlling the atherogenic disturbances. Four groups of male Wistar rats were fed with a high cholesterol diet (rat chow supplemented with 4% cholesterol and 1% cholic acid; HCD) for 30 days. Among them, 3 groups of rats were treated with either EPA (35 mg/kg body weight/day, oral gavage), LA (20 mg/kg body weight/day, oral gavage) or EPA-LA derivative (50 mg/kg body weight/day, oral gavage) from 16th day to 30th day of the experimental period. Abnormal increase in the levels of reactive oxygen species, 3-nitrotyrosine, malondialdehyde and protein carbonyl as well as an elevation in the activities of xanthine oxidase, lactate dehydrogenase, alkaline phosphatase and acid phosphatase was observed in renal tissue of HCD fed rats. HCD fed rats also showed an increased susceptibility of the apo B-containing lipoproteins to in vitro oxidation. These changes were restored partially in the EPA and LA administered groups. However, the combined derivative EPA-LA almost ameliorated the hypercholesterolemic-oxidative changes in the HCD fed rats.
AB - Hypercholesterolemia, an independent risk factor for increased oxidative renal injury, is associated with the formation of oxidized low-density lipoprotein. Production of reactive oxygen species and nitrogen species have been implicated in diet-induced hypercholesterolemia, principally as means of oxidising low-density lipoproteins. This inturn initiates the accumulation of cholesterol in macrophages, which sets key event in the initiation of atherosclerosis. The aim of the present work is to evaluate the effects of eicosapentaenoic acid (EPA), DL α-lipoic acid (LA) and eicosapentaenoate-lipoate derivative (EPA-LA) in controlling the atherogenic disturbances. Four groups of male Wistar rats were fed with a high cholesterol diet (rat chow supplemented with 4% cholesterol and 1% cholic acid; HCD) for 30 days. Among them, 3 groups of rats were treated with either EPA (35 mg/kg body weight/day, oral gavage), LA (20 mg/kg body weight/day, oral gavage) or EPA-LA derivative (50 mg/kg body weight/day, oral gavage) from 16th day to 30th day of the experimental period. Abnormal increase in the levels of reactive oxygen species, 3-nitrotyrosine, malondialdehyde and protein carbonyl as well as an elevation in the activities of xanthine oxidase, lactate dehydrogenase, alkaline phosphatase and acid phosphatase was observed in renal tissue of HCD fed rats. HCD fed rats also showed an increased susceptibility of the apo B-containing lipoproteins to in vitro oxidation. These changes were restored partially in the EPA and LA administered groups. However, the combined derivative EPA-LA almost ameliorated the hypercholesterolemic-oxidative changes in the HCD fed rats.
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U2 - 10.1016/j.plefa.2006.04.004
DO - 10.1016/j.plefa.2006.04.004
M3 - Article
C2 - 16737804
AN - SCOPUS:33746058991
SN - 0952-3278
VL - 75
SP - 25
EP - 31
JO - Prostaglandins Leukotrienes and Essential Fatty Acids
JF - Prostaglandins Leukotrienes and Essential Fatty Acids
IS - 1
ER -