Tissue Distribution of trans-Resveratrol and Its Metabolites after Oral Administration in Human Eyes

Abstract

Purpose. This study was performed to measure the concentration of trans-resveratrol and its three metabolites in human eyes. Methods. The patients who underwent pars plana vitrectomy for rhegmatogenous retinal detachment were included. The participants were orally given trans-resveratrol-based supplement (Longevinex®). A suitable amount of conjunctiva, aqueous humor, and vitreous humor were obtained during the operation. High-performance liquid chromatography (HPLC) with mass spectrometry (LC/MS/MS) was used to detect the concentration of trans-resveratrol and its three metabolites in the various samples. Results. The average concentration of resveratrol in the conjunctiva was 17.19 ± 15.32 nmol/g (mean ± SD). The concentration of resveratrol in the aqueous humor was close to the limit of detection, but its metabolites could be quantified. The concentrations of resveratrol metabolites in the aqueous humor can be detected. In the vitreous humor, the average concentration of resveratrol-3-O-sulfate was 62.95 ± 41.97 nmol/L. The sulfate conjugations of resveratrol were recovered in the conjunctiva, aqueous humor, and vitreous humor. Conclusions. Resveratrol and its three metabolites can be detected in the ocular tissues after oral administration. Although the concentration of parent resveratrol was low in the eyes, its metabolites could be detected and may have a role in the treatment of ocular diseases.

Figure 1

(a) Chemical structure of trans-resveratrol. (b) The structure of the metabolites of resveratrol: (1) R₁ = sulfate, R₂ = H: resveratrol-3-O-sulfate, (2) R₁ = H, R₂ = glucuronide: resveratrol-4′-O-glucuronide, and (3) R₁ = glucuronide, R₂ = H: resveratrol-3-O-glucuronide.

Figure 2

(A1) LC-MS chromatography of the aqueous humor of one patient who did not receive oral resveratrol. (A2) LC-MS chromatography of standard solution of resveratrol, its major three metabolites, and carbamazepine (internal standard). (A3) LC-MS chromatography of the aqueous humor of one patient who had taken one capsule daily for three days before tissue extraction. (B1) LC-MS chromatography of the vitreous humor of one patient who did not receive oral resveratrol. (B2) LC-MS chromatography of standard solution of resveratrol, its three major metabolites, and carbamazepine (internal standard). (B3) LC-MS chromatography of the vitreous humor of one patient who had taken one capsule daily for three days before tissue extraction. (C1) LC-MS chromatography of the conjunctiva of one patient who did not receive oral resveratrol. (C2) LC-MS chromatography of standard solution of resveratrol, its three major metabolites, and carbamazepine (internal standard). (C3) LC-MS chromatography of the conjunctiva of one patient who had taken one capsule daily for three days. 1: resveratrol-4′-O-glucuronide; 2: resveratrol-3-O-glucuronide; 3: resveratrol; 4: resveratrol-3-O-sulfate; and 5: carbamazepine.

Figure 3

(D1) LC-MS chromatography of the serum of one patient who did not receive oral resveratrol. (D2) LC-MS chromatography of standard solution of resveratrol, its major three metabolites, and carbamazepine (internal standard). (D3) LC-MS chromatography of the serum of one patient who had taken one capsule daily for three days before blood extraction.

Figure 4

The chromatograms and the related mass-to-charge ratio (m/z) of the total materials using chromatography combined mass spectrometry.