Gefarnate

Gefarnate

Gefarnate stimulates mucin-like glycoprotein secretion in conjunctival tissue and ameliorates corneal epithelial damage in animal dry-eye models

Purpose: The aim of this study was to evaluate the effect of gefarnate on mucin-like glycoprotein secretion in isolated rabbit conjunctival tissue, and on corneal epithelial damage in rabbit and cat dry-eye models.
Methods: Conjunctival tissue isolated from rabbits was treated with gefarnate. Mucin-like glycoprotein was detected in the culture supernatant by an enzyme-linked lectin assay. Gefarnate ointment was topically applied to eyes once daily for 7 days in the rabbit dry-eye model, in which the lacrimal glands, Harderian gland, and nictitating membrane were removed, or for 4 weeks in the cat dry-eye model, in which the lacrimal gland and nictitating membrane were removed. Corneal epithelial damage was evaluated by measurement of corneal permeability by rose bengal in the rabbit model or by fluorescein staining in the cat model.
Results: Gefarnate stimulated mucin-like glycoprotein secretion in conjunctival tissue in a dose-dependent manner. In the rabbit dry-eye model, application of gefarnate ointment to the eyes resulted in a dose-dependent decrease in rose bengal permeability in the cornea, with the effect being significant at concentrations of ≿.3%. In the cat dry-eye model, application of gefarnate ointment resulted in a significant decrease in the corneal fluorescein staining score.
Conclusion: These results suggest that gefarnate stimulates in vitro secretion of mucin-like glycoprotein in conjunctival tissue and ameliorates corneal epithelial damage in animal dry-eye models. Gefarnate may therefore be effective for treating dry eye.

Gastro-protecting effect of gefarnate on chronic erosive gastritis with dyspeptic symptoms

Background: The role of gastro-protecting agents on symptomatic chronic gastritis is unclear. This multicenter, open, randomized trial was designed to compare the comprehensive effects of gefarnate with sucralfate on erosive gastritis with dyspeptic symptoms.
Methods: Totally 253 dyspepsia patients confirmed with erosive gastritis were enrolled from six centers in China. They randomly received either daily 300 mg gefarnate or 3 g sucralfate for six weeks. The primary endpoint was the effective rate of both treatments on endoscopic erosion at week six.
Results: Gefarnate showed an effective rate of 72% and 67% on endoscopic score and dyspeptic symptom release, which is statistically higher than sucralfate (40.1% and 39.3%, P < 0.001, intension-to-treat). For histological improvement, gefarnate showed both effective in decreasing mucosal chronic inflammation (57.7% vs. 24.8%, P < 0.001, intension-to-treat) and active inflammation (36.4% vs. 23.1%, P < 0.05, intension-to-treat) than the control. A significant increase of prostaglandins and decrease of myeloperoxidase in mucosa were observed in gefarnate group. Severity of erosion is non-relevant to symptoms but Helicobacter pylori (H. pylori) status does affect the outcome of therapy.
Conclusions: Gefarnate demonstrates an effective outcome on the mucosal inflammation in patients with chronic erosive gastritis. Endoscopic and inflammation score should be the major indexes used in gastritis-related trials.

Gefarnate stimulates secretion of mucin-like glycoproteins by corneal epithelium in vitro and protects corneal epithelium from desiccation in vivo

The effect of drugs for gastritis and gastric ulcer (ecabet sodium, gefarnate, teprenone, and troxipide) on the secretion of mucin-like glycoproteins from rat cornea were investigated in vitro and on a short-term, rabbit dry eye model in vivo. For the studies in vitro, cultured rat cornea sections (3 mm diameter) were incubated with radiolabeled sodium sulfate, rinsed, and then incubated for 30 min in the presence of one of the drugs. The culture media were reacted with Dolichos biflorus agglutinate (DBA)-lectin, and the radioactivity of DBA-bound mucin-like glycoproteins was measured. A cytotoxicity assay confirmed that mucin-like glycoproteins had not leaked from damaged cells. For studies in vivo, eye drop vehicle or drops containing gefarnate were instilled in the eyes of nine anesthetized rabbits, and then the eyes were kept open with specula for two hours. These rabbits and two control rabbits not subjected to ocular drying were killed, and their eyes were enucleated and stained with methylene blue. Corneal epithelial damage from desiccation was evaluated based on the extent of methylene blue staining. Among the four kinds of drugs for gastritis and gastric ulcers, only gefarnate significantly increased the mucin-like glycoprotein secretion from cultured rat corneas in vitro; this stimulatory effect of gefarnate was dose-dependent. In vivo, the instillation of gefarnate reduced corneal epithelial damage from desiccation in a dose-dependent fashion. These results suggest that gefarnate reduces desiccation of corneal epithelium, perhaps by stimulating secretion of mucin-like glycoproteins from corneal epithelium.

Effect of gefarnate on the ocular surface in squirrel monkeys

Purpose: To investigate the ability of gefarnate (geranyl farnesylacetate) to stimulate goblet cell function in the primate eye after a mild alkali injury of the tarsal conjunctiva.
Methods: A bilateral injury was created on the conjunctival surface of the lower eye lid of squirrel monkeys by means of a 30-second application of a 4-mm diameter piece of filter paper wetted with 0.5% NaOH. Gefarnate drops (1%) were administered to one eye of each monkey and vehicle alone in the contralateral eye six times a day, 5 days a week for 4 weeks. Slit-lamp biomicroscopy, impression cytology staining of the ocular surface, fluorescein and rose bengal staining, and Western blot for mucin were performed before injury and weekly thereafter. Light microscopy was used to evaluate the lower conjunctiva.
Results: Topical application of gefarnate was not associated with any adverse ocular surface effects. Goblet cell repopulation after injury was significantly greater in the gefarnate-treated eyes compared with the vehicle-treated eyes. In the gefarnate-treated eyes, tear mucin content was significantly greater at 1 week after injury. Fluorescein staining was significantly reduced at 3 weeks after injury, and rose bengal staining was significantly reduced in the area of the wound at 2 weeks in the gefarnate-treated eyes compared with the vehicle-treated eyes; at other times, conjunctival staining in the two groups of eyes was not significantly different.
Conclusions: Gefarnate promotes goblet cell repopulation and increases mucin production after a conjunctival injury. No adverse affects of the treatment were found. Thus, this agent may be useful in conditions that diminish goblet cell function.