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.

Low testicular zinc level, p53 expression and impairment of Sertoli cell phagocytosis of residual bodies in rat subjected to psychological stress.

Psychological stress is a known aetiology of infertility. However, the mechanisms translating it to reproductive dysfunction are not fully elucidated. Three experiments were performed on Wistar rats were designed to evaluate Sertoli cell function under stress. In Experiment I, rats were randomised into three groups: saline baseline group given saline, ASEMA baseline group given aqueous extract of Massularia acuminata, zinc baseline group administered zinc orally. In Experiment II, exposure to psychological stress (for 1 hour per day) was layered on Experiment I while Experiment III substituted stress with administration of dexamethasone (DX). Six rats were sacrificed per group per experiment on days 7 and 14 and the right testis was excised and processed for PAS-haematoxylin staining and the left used for Zn determination. Results show significantly lower testicular Zn level as well more intensely immunoexpression of p53 in saline stress and saline DX groups compared with other groups. Also seen are the presence of residual bodies in the seminiferous tubular lumen of saline groups in Experiments II and III suggesting failure of residual bodies to be transported back towards the basement membrane. This study demonstrates that psychological stress impairs the ability of Sertoli cells to recycle residual bodies.