Beneficial Effects of Tibolone on Blood Pressure and Liver Redox Status in Ovariectomized Rats With Renovascular Hypertension

Abstract

Estrogen deficiency is associated with aging and increases the incidence of metabolic syndrome and hypertension. In this study, the effects of tibolone, a synthetic steroid, on the cardiovascular system, liver lipid metabolism, and redox status were evaluated, in ovariectomized (OVX) rats with renovascular hypertension (two-kidneys, one-clip, OVX + 2K1C). This study encompassed direct measurements of mean arterial pressure , plasma biochemical analysis, liver lipid contents, and assessments of the mitochondrial and peroxisomal β-oxidation capacities. Additionally, the liver redox status was assayed. Tibolone significantly reduced the mean arterial pressure of OVX + 2K1C rats, albeit reducing total and high-density lipoprotein (HDL) cholesterol levels. In the liver, although exerting an undesirable inhibition of mitochondrial and peroxisomal β-oxidation, tibolone reversed steatosis. Tibolone also improved the liver redox status: the reduced glutathione contents and the activity of glucose-6-phosphate dehydrogenase were restored by this compound, which also reduced the levels of thiobarbituric acid-reactive substances and the generation of mitochondrial reactive oxygen species. So, tibolone reversed the main alterations caused by hypertension and estrogen deficiency.

Tibolone Reverses NAFLD in Ovariectomised Rats by Reducing Adiposity and Insulin Resistance

“…Among the effects of tibolone in the liver redox state, the increases in GSH levels stand out, which were reduced in both the liver homogenate and isolated mitochondria of the OVX rats and were restored by treatment with tibolone. These results agree with previous studies performed by our team [45,48,55] and could be largely attributed to increases in mitochondrial ROS generation in the OVX rats [45,48,57]. Moreover, oxidative damage in the liver was also evidenced in the OVX rats by the higher levels of lipid peroxidation and carbonylated protein contents.…”

“…Recent studies performed in our laboratory revealed for the first time that tibolone was also effective in reversing NAFLD in hypertensive, OVX rats [45], by reducing the blood arterial pressure. So, although NAFLD has been considered, for a long time, as a IR-syndrome, recent studies have noted the importance of hypertension as a triggering factor of NAFLD [46,47].…”

“…So, although NAFLD has been considered, for a long time, as a IR-syndrome, recent studies have noted the importance of hypertension as a triggering factor of NAFLD [46,47]. In this regard, it should be noted that in those animals, NAFLD arose very early after the ovariectomy surgery (3 weeks), and independent on the IR, which was absent [15,45,48]. Thus, tibolone has been proven to be effective in reversing steatosis associated with IR, as evidenced in this work, as well as to be associated with hypertension, as previously demonstrated by us [45].…”

Goji Berry (Lycium barbarum) Extract Improves Biometric, Plasmatic and Hepatic Parameters of Rats Fed a High-Carbohydrate Diet

“…Another important feature of the HC diet is that the overload of TG in the hepatocytes leads to oxidative cellular damage [43]. Studies have shown that liver steatosis is linked to oxidative stress, including elevated production of mitochondrial ROS, decreased content of mitochondrial and cytosolic GSH, increased lipid peroxidation and decreased activity of antioxidant enzymes [20,44]. The liver of the HCD rats of this study displayed a similar profile, with increased mitochondrial ROS, reduced mitochondrial and cytosolic GSH and slightly higher lipid peroxidation.…”

Agnuside Reduces Visceral Adipocyte Size, Improves Insulin Sensitivity and Reverses Hepatic Steatosis in Ovariectomized Rats

“…Liver lipid metabolism is regulated by estrogens through genomic actions; thus, under conditions of estrogen deficiency, the incidence of NAFLD increases considerably [8]. The fat accumulation in the liver, in turn, leads to oxidative cell damage [9][10][11][12].…”