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INNOSC Theranostics and
Pharmacological Sciences Estrogen treatment reverse hypertension
MAP. These reductions are consistent with previous studies rats. This is evidenced by the significant elevation of AI
demonstrating that lipid control can play a crucial role in and CRI, as well as the significant reduction in the HDL/
managing hypertension and other metabolic syndrome- LDL cholesterol ratio. While these indices were mildly
related diseases. 32,33 elevated in OVX animals, consumption of thermoxidized
In addition, evaluation of ECG parameters revealed oil exacerbated them. ATV treatment reversed these effects
significantly prolonged QTc and QRS intervals in OVX + by significantly increasing the HDL/LDL cholesterol ratio
in OVX+TSO rats, and AI and CRI were significantly
TSO rats, and prolonged QRS, QT, and QTc in OVX+TPO decreased across all treatment groups. ETD administration
rats. This finding is consistent with an earlier report where effectively attenuated atherogenesis in OVX + TSO rats,
ovariectomy in rats affected all recorded ECG parameters. with a notable 75% decrease in AI. AI is a predictor of
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Prolonged QTc indicates cardiotoxicity and an elevated CVD risk, with a higher value indicating a heightened risk
risk of fatal cardiac arrhythmias. 35,36 A decreasing trend of atherosclerosis. Treatments with ETH, ATV, and EZE
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in QRS, QT, and QTc intervals was observed across all significantly decreased AI and CRI, though their effects on
treatment groups, suggesting a cardioprotective effect. the HDL-c/LDL-c cholesterol ratio were less pronounced.
TPO increases CVD risk, as evidenced by the significant
increase in heart rate, QRS, QT, and QTc. Treatment These results suggest that early administration of low-
with antihyperlipidemic drugs offers cardioprotection, dose ETD and antihyperlipidemic drugs in individuals
as demonstrated by the significant decrease in heart rate exposed to CVD risk factors, such as menopause and
and reductions in QRS, QT, and QTc upon completion of thermoxidized oil consumption, can reduce the risk of
treatment with ATV and EZE + ATV. CVDs.
Evaluation of serum lipid profile and atherogenic indices Previous studies have proposed that hypertension is an
revealed the development of hyperlipidemia, characterized inflammatory disease and have explored the possible links
by hypercholesterolemia, hypertriglyceridemia, and between oxidative stress, hypertension, and CVDs. 40,41
overproduction of VLDL, following ovariectomy and Oxidative stress occurs when there is an imbalance
thermoxidized oil treatment. The significant increases between free radicals and the cellular antioxidant
in total cholesterol, triglycerides, VLDL, and LDL-c in system, with pro-oxidant molecules overwhelming the
levels in the diet-only groups support this finding. These system. Vascular oxidative stress is one of the leading
results also suggest the presence of metabolic syndrome factors for CVDs. 42,43 It is implicated in endothelial
in these groups. Treatments with ATV, EZE + ATV, and dysfunction, which is an initial step in the development
ETD effectively reversed hyperlipidemia in OVX + TSO of atherosclerosis and other CVDs. The generation of
rats. ATV and ETD significantly decreased VLDL levels, reactive oxygen species (ROS) and the degradation of
whereas EZE + ATV and ETD treatments significantly nitric oxide are major outcomes of oxidative stress. This
increased HDL-c levels. HDL-c plays a crucial role process promotes endothelial dysfunction by reducing
in reverse cholesterol transport by scavenging excess endothelium-mediated vasorelaxation and disrupting the
cholesterol from tissues and transporting it to the liver non-thrombogenic surface of the endothelium, exposing
for metabolism and excretion. This action of HDL-c can the vessel wall to thrombogenic components in the
attenuate oxidized LDL-mediated atherogenic progression blood. 44,45 Impairment of endothelial vasodilation due to
in the artery walls. Similarly, ETD and antihyperlipidemic endothelial dysfunction disrupts the regulation of vascular
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drug treatments reversed hyperlipidemia in OVX + TPO tone, potentially resulting in paradoxical vasoconstriction,
rats. This was evident from the significant reductions in cardiac ischemia, heart failure, increased renal vascular
triglyceride and VLDL levels across all treatment groups. constriction, sodium reabsorption, and hypertension. 40,44
In addition, EZE + ATV significantly increased HDL-c In this study, serum levels of GSH, MDA, CAT, and SOD
levels, while ETD treatment significantly decreased were examined as markers of oxidative stress in OVX rats
triglyceride levels. Overproduction of VLDL is a hallmark fed TSO and TPO.
of dyslipidemia in metabolic syndrome. Increased The findings of this study suggest that ovariectomy
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VLDL levels negatively impact the composition of HDL, alone does not significantly impact oxidative stress.
facilitating its degradation through the actions of hepatic However, treatment with thermoxidized oils increases
lipase and cholesterol ester transfer protein. Thus, ROS production and disrupts redox balance, as revealed
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reducing VLDL levels helps preserve HDL-c concentration. by the results of this study.
Ovariectomy and thermoxidized oil treatment appear Treatment with ETD appeared to normalize lipid
to increase the risk of developing atherosclerosis and metabolism and reduce ROS production in both the TSO
coronary artery disease in OVX+TSO and OVX+TPO and TPO diet groups. These results support previous
Volume 7 Issue 4 (2024) 7 doi: 10.36922/itps.3901

