Characterization of glutathione uptake, synthesis, and efflux pathways in the epithelium and endothelium of the rat cornea.

PURPOSE: To compare and contrast glutathione (GSH) uptake, synthesis, and efflux pathways in the epithelium and endothelium of the rat cornea. METHODS: Whole eyes were cryosectioned in an equatorial orientation and sections fixed in either 0.75% paraformaldehyde alone or 0.75% paraformaldehyde plus 0.01% glutaraldehyde. Sections were then labeled with GSH, γ-glutamylcysteine synthetase (γ-GCS), cysteine, xCT, or multidrug resistance-associated proteins (MRP1, 2, 4, and 5 isoforms) antibodies and then with secondary antibodies to visualize labeling patterns. Cornea morphology was visualized using propidium iodide. Reverse transcriptase-polymerase chain reaction was used to determine which of the 3 putative GSH transporters, NaDC3, C-terminal organic anion transporter 1 (OAT1), and/or N-terminal organic anion transporter 3 (OAT3), were present at the transcript level in the cornea. Colocalization of OAT3 and sodium dependent dicarboxylate transporter 3 (NaDC3) was performed by labeling with OAT3 and NaDC3 primary antibodies that were visualized with secondary antibodies and then mounted in 4'6-diamidino-2-phenylindole to visualize cell morphology. RESULTS: Although immunohistochemical labeling showed GSH to be localized throughout the cornea, labeling for cysteine, γ-GCS, xCT, MRP4, and MRP5 was strongest in the epithelium. In contrast, although GSH labeling was strong in the endothelium, xCT and MRP labeling was absent and cysteine and γ-GCS labeling was weak relative to the epithelium. Reverse transcriptase-polymerase chain reaction revealed OAT3 and NaDC3, but not OAT1, to be present at the transcript level. Immunohistochemical labeling showed OAT3 and NaDC3 to be localized to the endothelium but absent from the epithelium. CONCLUSIONS: The corneal epithelium and endothelium exhibit differences in GSH uptake, synthesis, and efflux pathways. The corneal epithelium seems to be the region where GSH synthesis and GSH efflux occurs. However, in the endothelium, GSH accumulation is likely to be predominantly by direct uptake of GSH from the aqueous humor.

Potential interactions between herbal medicines and conventional drug therapies used by older adults attending a memory clinic.

OBJECTIVE: Herbal medicines and conventional drug therapies are often taken in combination. The objective of our study was to identify the range of natural health products and conventional drug therapies used by older adults (aged 65 years and over) attending a memory clinic, and to specifically evaluate the frequency of potential interactions between herbal medicines and conventional drug therapies. DESIGN: We interviewed consecutive patients attending the Memory Disorders Clinic at the Baycrest Centre for Geriatric Care, a University of Toronto teaching hospital, between 4 July and 15 August 2000. Patients were asked to bring to their appointment all natural health products (i.e. herbal medicines, vitamins and minerals) and conventional drug therapies (i.e. prescription and over-the-counter) they were currently using. We collected information on current and previously used natural health products and current conventional drug therapies. Patients were classified as having the potential for an interaction if they were using a current herbal medicine in combination with a conventional drug therapy and the interaction had been reported previously in the medical literature. PARTICIPANTS: We interviewed 195 consecutive patients attending the Memory Disorders Clinic at the Baycrest Centre for Geriatric Care, Toronto, Ontario, Canada. RESULTS: Of the 195 patients in our sample, 33 (17%) were 'current users', 19 (10%) were 'past users', and 143 (73%) were 'never users' of herbal medicines. Among the 52 patients who were 'current or past users', the most frequently used herbal medicines were ginkgo (Ginkgo biloba) [39 users], garlic (n = 10), glucosamine sulphate (n = 9) and echinacea (n = 8). Among the 33 patients who were current users, the most commonly used herbal medicines were Ginkgo biloba (n = 22), glucosamine sulphate (n = 8) and garlic (n = 6). Among the 33 current users, we identified 11 potential herb-drug interactions in nine patients. The 11 herb-drug interactions we identified were between ginkgo and aspirin (acetylsalicylic acid) [n = 8], ginkgo and trazodone (n = 1), ginseng and amlodipine (n = 1) and valerian and lorazepam (n = 1). CONCLUSIONS: Herbal medicines are widely used. Almost one-third of current users of herbal medicines were at risk of a herb-drug interaction. The most common potential herb-drug interaction was between ginkgo and aspirin. This finding has important potential implications because both of these products are regularly used by older people. Physicians and other healthcare providers should be aware of potential herb-drug interactions and should monitor and inform their patients accordingly.