Evaluation of the Presence and Functional Importance of Nucleoside Transporters in Lacrimal Gland for Tear Disposition of Intravenously Injected Substrate in Rabbits

ABSTRACT

Purpose: Purpose of the current study was to assess the presence and functionality of the nucleoside transporters in the lacrimal gland for the tear disposition of its substrate given intravenously in rabbits.

Materials and Methods: Rabbits were divided into two groups – control and blocker pretreated. The blocker pretreated group received 5 mg/kg of dipyridamole 30 min before ribavirin (substrate), which was given at a dose of 2.5 mg/kg. All the treatments were given intravenously. Blood and tear samples were collected at 5, 15, 30, 60, 90, 120, 180, 240, 300 and 360 min (n = 4; each time point) after substrate administration. Tear samples were collected on Schirmer’s strips, and plasma was separated immediately after blood collection. All the samples were stored at −80°C until analysis by LC-MS/MS.

Results: Plasma ribavirin concentration for blocker pretreated group showed significantly (p < .05) higher levels at 5, 15, 30, 60, 120, 180 and 300 min as compared to the control group. Similarly, tear ribavirin concentration for blocker pretreated group also showed a significant (p < .05) increase at 5, 15, 60, 90, 180, 240 and 300 min compared to the control group. Plasma and tear AUC_(0–6) for blocker pretreated group was 1.7 (p < .001) and 2.42 (p < .001) folds higher in a significant manner as compared to the control group, respectively. Percentage penetration of ribavirin from plasma to tears was also different between control and blocker pretreated group. Permeation ratio of ribavirin from plasma to tear for blocker pretreated group was found to be 1.4-folds higher in a significant (p < .05) manner.

Conclusion: It is evident from the results that nucleoside transporters are present in lacrimal gland. The blocker treatment induced increase in tear transport of ribavirin indicates the possibility of the presence of nucleoside transporters on the apical side of lacrimal acinar cells in the uptake position.

KEYWORDS:

• Lacrimal gland
• ribavirin
• CNT
• ENT
• rabbit
• intravenous

Acknowledgments

We acknowledge the Council of Scientific & Industrial Research (CSIR), India, for Providing Senior Research Fellowship to Mr. Hanuman Prasad Sharma. We also thank Mr. Kunwar Kanhiya and Ms. Bhawna Arora for the animal care and handling during in vivo experiments.

Additional information

Funding

This work was supported by All India Institute of Medical Sciences, New Delhi, under intramural grant [F.5-59/IRG/2010/RS].