Cimicifuga racemosa impairs fatty acid β-oxidation and induces oxidative stress in livers of ovariectomized rats with renovascular hypertension

Abstract

The aim of this work was to evaluate the effects of therapeutic doses of Cimicifuga racemosa on cardiovascular parameters and on liver lipid metabolism and redox status in an animal model of estrogen deficiency associated with hypertension, a condition that could make the liver more vulnerable to drug-induced injuries. Female Wistar rats were subjected to the surgical procedures of bilateral ovariectomy (OVX) and induction of renovascular hypertension (two-kidneys, one-clip; 2K1C). These animals (OVX + 2K1C) were treated with daily doses of a C. racemosa extract, using a dose that is similar to that recommended to postmenopausal women (0.6 mg/kg), over a period of 15 days. The results were compared to those of untreated OVX + 2K1C, OVX, and control rats. The treatment with C. racemosa caused a significant reduction in blood pressure. In the liver, treatment did not prevent the development of steatosis, and it reduced the mitochondrial and peroxisomal capacity to oxidize octanoyl-CoA compared to the untreated animals. In addition, C. racemosa caused numerous undesirable effects on the liver redox status: it increased the mitochondrial reactive oxygen species generation, an event that was not accompanied by an increase in the activity of superoxide dismutase, and it induced a decrease in peroxisomal catalase activity. Although the reduced glutathione content had not been affected, a phenomenon that probably reflected the restoration of glucose-6-phosphate dehydrogenase activity by C. racemosa, oxidative damage was evidenced by the elevated level of thiobarbituric acid-reactive substances found in the liver of treated animals.

Acute toxicity and long-term safety evaluation of the crude extract from rhizomes of Limonium brasiliense in mice and rats

“…This organ is a frequent target of drug action, and drug-induced hepatotoxicity (drug-induced liver injury or DILI) is a common cause of liver failure and withdrawal of drugs (Labbe et al, 2008). Many substances produce hepatotoxicity by directly or indirectly inducing oxidative stress (Berson et al, 1998;Campos et al, 2012;Fromenty and Pessayre, 1995;Labbe et al, 2008). The evaluation of the liver of the females, however, showed that the extract did not produce changes in the redox state of this organ.…”

“…The content of reduced glutathione (GSH) was analyzed in the supernatant, using o-phthalaldehyde (OPT) as a fluorescent probe in a spectrofluorimeter (excitation 350 nm, emission 420 nm) (Campos et al, 2012;Hissin and Hilf, 1976) and used as an indicator of the redox state of the liver.…”

“…Lipid peroxidation levels in the livers were also evaluated by direct spectrophotometry, by determining the concentration of thiobarbituric acid-reactive substances (TBARS), which are considered biomarkers of lipid peroxidation and oxidative damage (Campos et al, 2012;Ohkawa et al, 1979).…”

“…Several substances or metabolic disorders may induce oxidative stress in their very early stages (Berson et al, 1998;Campos et al, 2012;Charlton et al, 2001;Day and James, 1998;Fromenty and Pessayre, 1995;Kowaltowski et al, 2009;Labbe et al, 2008). Oxidative damage, in turn, is considered to be the main factor involved in the progression of liver disease (Day and James, 1998).…”

Chemical and biological studies of Cimicifugeae pharmaceutical resources

“…CR impairs fatty acid b-oxidation and induces oxidative stress in livers of ovariectomized rats with renovascular hypertension (Campos et al, 2012). Quality problems in a few CR products were evident that require additional regulatory quality specifications (Teschke et al, 2011).…”