Bioactivity and metabolism oftrans-resveratrol orally administered to Wistar rats

Abstract

The purpose of this study was to investigate the implications of selected chemopreventive parameters and metabolic conversion of resveratrol in vivo. In two 8-week long feeding experiments with rats, a low-resveratrol diet containing 50 mg resveratrol per kg body weight (bw) and day and a high-resveratrol diet with 300 mg per kg bw and day were administered. For chemopreventive evaluation selected phase I and phase II enzymes of the biotransformation system, the total antioxidant activity, and the vitamin E status of the animals were determined. The level of resveratrol and its metabolites in the feces, urine, plasma, liver, and kidneys was identified and quantitated by high-performance liquid chromatography-diode array detection (HPLC-DAD) using synthesized resveratrol conjugate standards. Feeding of different dosages of resveratrol revealed no effect on the different chemopreventive parameters, except for the total antioxidant activity, which was elevated in plasma by 19% after feeding 50 mg resveratrol per kg bw and day. The formation of trans-resveratrol-3-sulfate, trans-resveratrol-4'-sulfate, trans-resveratrol-3,5-disulfate, trans-resveratrol-3,4'-disulfate, trans-resveratrol-3,4',5-trisulfate, trans-resveratrol-3-O-beta-D-glucuronide, and resveratrol aglycone was detected by HPLC analysis, depending on the biological material. Total resveratrol recovery in urine and feces of rats fed on 50 mg resveratrol per kg bw and day was 15% and 13%, respectively. For rats fed the higher dosage of 300 mg resveratrol per kg bw and day recovery was 54% and 17%, respectively. This is the first study performed with synthesized standards of relevant resveratrol conjugates. The lack of effect on the chemopreventive parameters is probably due to the formation of various resveratrol conjugates reducing its bioavailability in the rat.

Does Resveratrol Have a Protective Effect on Tympanosclerosis Formation in Experimentally Induced Otitis Media?

“…No significant differences between Groups were recorded. This result is consistent with the literature in showing that oral administration of resveratrol is not harmful at the dosage and for the period administered [12,13,32] .…”

“…It modulates lipid and lipoprotein metabolism and is a potent chemopreventive agent. It also has antioxidant and anti-inflammatory properties [12,13] . Seidman et al [17,18] demonstrated the effectiveness of resveratrol against noise-induced hearing loss in two studies.…”

“…Resveratrol has anti-inflammatory, antioxidant, anticarcinogenic, and anti-ageing properties [12,13] . Although the protective effects of resveratrol against cisplatin-induced ototoxicity and noise-induced hearing loss were reported in recent studies [14][15][16][17][18] , there have been no published studies on the possible role of resveratrol in the prevention of TS.…”

N-Monosubstituted Methoxy-oligo(ethylene glycol) Carbamate Ester Prodrugs of Resveratrol

“…Indeed, the modifications just mentioned have been long recognized and studied for representative members of this huge family of natural compounds, including resveratrol, which is of specific interest here. Rapid glucuronidation and sulfation in enterocytes, hepatocytes, and other cells (e.g., [14][15][16][17][18][19][20][21]) and re-export to the intestinal lumen by MDR proteins [15,22,23], or possibly OATPs [24], are thought to limit the potential impact of this celebrated "natural drug" in vivo. This is a pity, given the pleiotropic effects this dietary compound is reported to have in important pathophysiological respects (for recent reviews see, e.g., [25][26][27][28][29][30]).…”

The Inhibitory Effect of Natural Stilbenes and Their Analogues on Catalytic Activity of Cytochromes P450 Family 1 in Comparison with Other Phenols - Structure and Activity Relationship

“…Recently, interest in the combinatory effect of different phytochemicals is growing, with respect to the multi-targeted action of numerous components of a food matrix. Wenzel and co-workers found that metabolism of resveratrol present in beverages such as wine or grape juice is inhibited by other polyphenols due to competitive reactions with Phase -II enzymes, resulting in an increased concentration of the free form (Wenzel et al, 2005). It is suggested that an efficient chemoprevention strategy lies in the use of combinations of several chemopreventive and/or therapeutic agents which may exert multi-targeted action.…”