Effect of Dietary Doses of Quercetin on Hepatic Drug Metabolizing Enzymes in Spontaneously Hypertensive Rats.

BACKGROUND: Administration of quercetin (QR) has shown several health benefits in clinical and pre-clinical studies. OBJECTIVE: This study investigates the effect of dietary doses of QR on hepatic drug metabolizing enzymes in spontaneously hypertensive rats in order to investigate the potential for herb-drug interactions. METHODS: The activity and/or protein expression of selected cytochrome P450 (CYP) enzymes and microsomal epoxide hydrolase were measured in hepatic microsomes using specific probe substrates and/or polyclonal antibodies. Cytosolic fraction was utilized to measure protein level and activity of major antioxidant systems. RESULTS: The doses employed in our study did not cause any significant alterations in the activity and/or protein level of CYP1A1, CYP2A6, CYP2E, and glutathione (GSH). While the activity and apoprotein levels of CYP1A2 and CYP2B1/2 were significantly reduced by the medium and high doses of QR, the activity and/or protein level of microsomal CYP3A and cytosolic GSH-S-transferase, GSH reductase, and GSH peroxidase were significantly enhanced. Activity and protein level of CYP2C9 were significantly inhibited by all doses. Only the high-dose QR resulted in significant inhibition of both microsomal and soluble epoxide hydrolase as well as induction of the antioxidant enzymes, catalase and superoxide dismutase. CONCLUSION: This study demonstrates that dietary doses of QR may offer chemoprevention through stimulation of the endogenous antioxidant systems and inhibition of CYP enzymes involved in bioactivation of procarcinogens. However, modulation of drug metabolizing enzymes by QR could have potential for herb-drug interactions with the possibility of serious complications.

The effect of multivitamin-multimineral supplementation on the health status of inbred Wistar and spontaneously hypertensive rat strains.

The nutraceutical industry has proliferated in recent years, with the most popular form of supplementation being the multivitamin-multimineral (MVMM) supplement. In the animal health sector, supplement use has also expanded. The objective of this study was to determine the effects of MVMM supplementation, beneficial or otherwise, on the general health status of the spontaneously hypertensive rat (SHR) strain, an animal model used in hypertension research. A commercially prepared MVMM supplement was given tri-weekly via oral dosing for 8 weeks to two groups of seven adult female SHR and Wistar rats. Their corresponding control groups were dosed with deionised water only. Systolic and diastolic blood pressure, fasting blood glucose, growth rate and food and water intake were measured weekly. At the end of 8 weeks, the animals were euthanased and a full blood profile, urine sodium to potassium ratio, blood urea nitrogen levels and total plasma cholesterol was measured for all groups. The results indicated that growth rate was higher for the SHR supplemented group. Supplementation also decreased diastolic blood pressure in both Wistar and SHR groups and increased red blood cell count and decreased total cholesterol in the SHR group. No adverse effects on the general health status of the animals were observed. MVMM supplementation may therefore be useful in aiding growth and delaying the onset of hypertension and its effects. It may also assist in the longevity of the breeding stock of SHR rats.

Prolongation of life span in hypertensive rats by dietary interventions. Effects of garlic and linseed oil.

The effects of long-term dietary application of garlic (dried powder, 0.5% in weight of standard chow; G group) or linseed oil (2.5%; L group) as well as a combination of both interventions (L + G group) on the life span of hypertensive rats (SHR SP) was investigated. A further group fed with standard chow served as control (C). The dietary interventions were started at the age of three weeks. Besides regular measurements of the systolic arterial blood pressure (oscillometrically at the tail artery) as well as of heart rate and body weight, autopsy and histological investigations were performed. Both diets, and particularly their combination, prolonged life span significantly (mean values (days) C: 434.5 +/- 23.5; G: 453.2 +/- 16.2; L: 470.0 +/- 26.2; L + G: 494.8 +/- 39.2). There was no significant interaction of the factors garlic and linseed oil. Systolic blood pressure as measured during the compensatory stage (data used until the 39th week of life) was significantly lowered by both garlic (mean -5.8 mm Hg), linseed oil (mean -6.3 mm Hg), and their combination (mean -11.3 mm Hg). The animals died as a consequence of congestive left and right ventricular failure with ventricular hypertrophy, dilatation, myocardial fibrosis and cellular infiltration, left ventricular atrial thrombosis (in most cases), and terminal pneumonia. On the other hand, arteriosclerotic plaques and signs of cerebral stroke could not be detected. Except for the degree of hypertrophy, which was lower in the treated groups, no differences were obvious regarding the morphological findings at the time of death. There was a significant positive correlation between mean blood pressure and the degree of left ventricular hypertrophy. Furthermore, a significant negative correlation between mean blood pressure and ventricular hypertrophy on the one hand and survival on the other hand was obvious provided the total number of animals was considered, however, not within the individual groups. The same applies to the relation between the reduction of left ventricular hypertrophy and life span. The relatively slight hypotensive effect of both dietary interventions as well as the results of previous investigations speaks in favor of a substantial influence of factors independent of blood pressure. In view of controversial results and interpretations in international literature, the mechanisms involved need further study.

Neurotransmitters and neuropeptides in blood pressure regulation in the spontaneously hypertensive rat.

Studies of the roles played by neurotransmitters in the development of hypertension in the spontaneously hypertensive (SHR) rat are complicated by the presence of genetic differences between SHR and normotensive control rats, which are not related to differences in blood pressure. One approach that may be used in an attempt to overcome this difficulty is to study the manner in which neurotransmitter and metabolite levels change with age, and to relate these changes to alterations in blood pressure with ageing. Noradrenaline (NA) levels in the brainstem and spinal cord of SHR and Wistar Kyoto rats fell with age, while 3,4-dihydroxyphenylethyleneglycol (DHPG) levels (a neuronal metabolite of noradrenaline) remained constant. Similar changes were seen when NA and DHPG levels were measured in the discrete brainstem A1, A2, and C2 region, and when adrenaline, NA, and DHPG levels were examined in the C1 region. Differences in age-related changes of neuropeptide Y (NPY) levels were also found in the ventromedial nucleus of the hypothalamus and the locus coeruleus, and of beta-endorphin in the anterior hypothalamic nucleus, the paragigantocellular nucleus of the brainstem, and the locus coeruleus. These changes may indicate either a progressive increase in the activity of neurons in the sympathoexcitatory C1 region or a progressive reduction in the activity of vasodepressor A1, A2, and C2 regions with ageing, or both. However, changes in catecholamines and metabolites with age were similar in both strains and therefore cannot readily explain the more rapid rise in blood pressure with ageing in SHR rats.