Effect of Valsartan and Folic Acid on Vascular Reactivity, Leptin Hormone and Some Biochemical Parameters in Fat Diet-Induced Obese Male Rats

Abstract
Background: The development of a chronic low-grade inflammatory state has been shown to play a central role in the development of metabolic complications associated with obesity.
Aim of Study: The aim was to determine the impact of oral administration of valsartan and folic acid to fat diet-induced obese male rats on the vascular reactivity & on the serum levels of leptin and some inflammatory and oxidative stress markers.
Material and Methods: Fifty male albino rats of local strain were randomized into five equal groups: Control, obese, valsartan-treated obese, folic acid-treated obese and combined valsartan and folic acid-treated obese groups. Obesity was induced by feeding high fat diet and treatment was done for indicated groups for 16 weeks. Thereafter, weight and length were measured, and rats were subjected for rat tail-measurement of Systolic Blood Pressure (SBP). Then, fasting retro-orbital blood samples were collected for measuring serum Total Cholesterol (TC), Triglycerides (TGs), Low Density Lipoprotein-Cholesterol (LDL-C), High Density Lipoprotein-Cholesterol (HDL-C), Malondialdehyde (MDA), C-Reactive Protein (CRP) and leptin levels, as well as serum Glutathione Peroxidase (GPx) and Superoxide Dismutase (SOD) activities, andurinary nitrite/nitrate (NOx) level. Rats were tested for Vascular Reactivity to Acetylcholine (VRACh) and sodium nitroprusside (VRSNP) by Doppler flowmeter. Lastly, rats were sacrificed and abdominal visceral fats were resected and weighed.
Results: High fat diet resulted in marked impairment of all the measured parameters, except VRSNP. Treatment of obese rats with valsartan resulted in improvement of BMI, adipose tissue mass, TC, LDL, CRP, leptin, NOx, MDA, SBP and VRACh; however, total body weight, TGs, HDL-C and antioxidant enzyme activities were not affected. Folic acid administration to obese rats improves all serum lipid param-eters, increased GPx and SOD activities, and showed a better effect than valsartan on NOx, leptin andVRACh, but less effect on CRP. On the other hand, folic acid had no effect on the anthropometric parameters and SBP of obese rats. Com-bined treatment showed a reduction in total body weight, and a significant better improvement of all the measured parame-ters, except MDA, than those of isolated valsartan or folic acid treatment, with normalization of MBI, TGs, LDL-C, NOx and VRACh.
Conclusion: Both valsartan and folic acid, when admin-istered separately, ameliorate the detrimental effects of fat diet-induced obesity in rats. Combined valsartan and folic acid prophylactic treatment of fat diet-induced obese rats has an additive beneficial effect on the associated dyslipidemia, inflammatory state, oxidative stress, leptin hormone level, and endothelial dysfunction that is possibly achieved by different mechanisms of action.