Oxidized dietary lipids induce vascular inflammation and atherogenesis in post-menopausal rats: estradiol and selected antihyperlipidemic drugs restore vascular health in vivo.

BACKGROUND: Thermoxidation of edible oil through deep fat frying results in the generation of several oxidized products that promote lipid peroxidation and ROS production when eaten. Consumption of thermoxidized oil in post-menopausal conditions where the estrogen level is low contributes to cardiovascular disease. This study evaluates the role of estradiol and antihyperlipidemic agents (AHD) in restoring the vascular health of ovariectomized (OVX) rats fed with thermoxidized palm oil (TPO) and thermoxidized soya oil (TSO) diets. METHOD: A total of 10 groups of rats (n = 6) were set up for the experiment. Group I (normal control) rats were sham handled while other groups were OVX to bring about estrogen deficient post-menopausal state. Group II (OVX only) was not treated and received normal rat chow. Groups III-X were fed with either TPO or TSO diet for 12 weeks and treated with estradiol (ETD) 0.2 mg/kg/day, atorvastatin (ATV) 10 mg/kg/day, and a fixed-dose combination of ezetimibe and ATV (EZE 3 mg/kg/day + ATV 10 mg/kg/day). RESULTS: Pro-atherogenic lipids levels were significantly elevated in untreated TSO and TPO groups compared to OVX and sham, resulting in increased atherogenic and Coronary-risk indices. Treatment with Estradiol and AHDs significantly reduced the total cholesterol, triglycerides, low-density lipoprotein cholesterol as well as AI and CRI compared to untreated TSO and TPO groups, whereas TSO and TPO groups showed significant elevation in these parameters compared to Group I values. Moreover, aortic TNF-α levels were extremely elevated in the untreated TSO and TPO compared to Group I. TNF-α levels were significantly reduced in rats treated with AHDs and ETD. Localized oxidative stress was indicated in the aortic tissues of TSO and TPO-fed OVX rats by increased malondialdehyde and decreased glutathione, catalase, and superoxide dismutase levels. This contributed to a depletion in aortic nitric oxide. AHDs and ETD replenished the nitric oxide levels significantly. Histological evaluation of the aorta of TSO and TPO rats revealed increased peri-adventitia fat, aortic medial hypertrophy, and aortic recanalization. These pathologic changes were less seen in AHDs and ETD rats. CONCLUSION: This study suggests that ETD and AHDs profoundly attenuate oxidized lipid-induced vascular inflammation and atherogenesis through oxidative-stress reduction and inhibition of TNF-α signaling.

Combined Intranasal Insulin/Saxagliptin/Metformin Therapies Ameliorate the Effect of Combined Oral Contraceptive- (COC-) Induced Metabolic Syndrome (MetS) with a Major Target on Glucose Metabolism in Adult Female Wistar Rats.

OBJECTIVE: To evaluate the effect of the chronic use of combined oral contraceptives (COCs: ethinyl estradiol and levonorgestrel) on the indices of metabolic syndrome in adult female Wistar rats and possible therapeutic management. MATERIALS AND METHODS: 64 female Wistar rats received either distilled water, norethindrone (NOR), COC, intranasal insulin (INI), metformin (MET), saxagliptin (SAX), INI+MET, and INI+SAX. After 8 weeks of exposure to COC, the animals were sorted into the therapeutic groups. Several parameters were assayed for, such as body weight changes, fasting blood glucose (FBG) level, insulin levels, inflammatory cytokines, and glycated hemoglobin (Hb1Ac). RESULTS: The levels of FBG, insulin, and Hb1Ac were increased consequent upon COC treatment. Treatment with INI+SAX and INI+MET reduced significantly the levels of FBG and Hb1Ac; in addition, the level of insulin was significantly increased in the INI+MET groups (p ≤ 0.05). Serum lipid profile analysis showed a statistical reduction in high-density lipoprotein (HDL) level; this reduction was also significantly reversed in the INI+SAX group. Reduced catalase activity observed in the COC group was reversed in the INI+MET group (p ≤ 0.05). A nonsignificant increase in the level of TNF-α as a result of COC treatment was reversed by INI and INI+MET treatment. Liver GLUT4 and G-6-phosphate levels were significantly increased by COC treatment, and this effect was reversed by INI+SAX in both assays, respectively (p ≤ 0.01). CONCLUSIONS: The use of MET and SAX in combination with INI has been shown to reverse some indices of MetS. This study proposes a clinical phase to backup and ascertain these preclinical findings.

Antidiabetic and antihyperlipidemic effects of aqueous extract of Parquetina nigrescens in streptozotocin-nicotinamide induced type 2 diabetic rats.

BACKGROUND: Parquetina nigrescens is among the evergreen plants native to West Africa. It is used in the management of various ailments including anemia, fever, asthma and diabetes. This study evaluated the antidiabetic and antihyperlipidemic effect of Parquetina nigrescens in streptozotocin-nicotinamide-induced type 2 diabetic rats. METHODS: Type 2 diabetes mellitus was induced in overnight fasted rats with a single intraperitoneal injection of streptozotocin (60 mg/kg), followed by the administration of nicotinamide (120 mg/kg) after an interval of 15 min. Diabetic rats were orally administered with; 200, 400 and 800 mg/kg of aqueous extract of Parquetina nigrescens (AEPN), metformin (180 mg/kg) and glibenclamide (1 mg/kg) for two weeks. The effect of treatments on fasting blood glucose, serum insulin, leptin, adiponectin, homa-ir, lipid profile, body weight, pancreatic antioxidants parameters, hepatic glycogen content, glucose-6-phosphate activity, α-amylase inhibition, α-glucosidase inhibition, lipase inhibition and histology of the organs were evaluated. RESULTS: Data from this study showed that treatment with AEPN produced a significant reduction (p < 0.05) in fasting blood glucose, glucose-6-phosphatase activity, serum lipase, total triglyceride, total cholesterol, low-density lipoproteins, very low-density lipoprotein, atherogenic index, coronary risk index, pancreatic α-amylase, α-glucosidase and lipase activities. Treatment with AEPN also produced a significant (p < 0.05) increase in; glucose tolerance, glycogen content, leptin, adiponectin and pancreatic antioxidants (glutathione, superoxide dismutase, catalase and high-density lipoproteins). The histology of the organ showed regeneration of the pancreatic tissue after treatment with AEPN. CONCLUSIONS: This study showed that AEPN exhibited antidiabetic and antihyperlipidemic activity in streptozotocin-nicotinamide-induced type 2 diabetic rats.