Passive absorption across gastrointestinal tissues in vitro and postharvest distribution of loline alkaloid in lambs

Abstract

Loline alkaloid has suggested antimicrobial and anthelmintic properties with very low mammalian toxicity. There are several known derivatives of loline; N-formyl loline (NFL), N-acetyl loline (NAL), N-acetyl norloline (NANL), N-methyl loline (NML), and loline base. However, these must reach the abomasum or intestine and then be absorbed to have any potential effect. Therefore, passive absorption in isolated gastrointestinal tissues and distribution in the tissue of lambs were determined. Experiment 1: Lamb (n = 6) isolated gastrointestinal tissues were removed and mounted in an Ussing chamber. Approximately, 1 034 µg/g of loline and 22.1 µg/mL of caffeine were added to the donor chamber to measure loline flux at 0, 0.5, 1, and 2 hours. Experiment 2: Two, 12-week-old lambs were dosed with 52.5 mg/kg BW loline twice and were slaughtered to determine the distribution in gastrointestinal, organs, and blood. Passive absorption was 5% in ileum, <2% in ruminal or abomasal tissues. Loline base and NFL were passively absorbed across all tissues, with NAL and NANL only crossing small intestine tissues. Surprisingly, no caffeine crossed any tissues. Loline base and small amounts of NFL were in blood plasma, and loline base was also found in liver and kidneys. Results indicate either the majority of loline is not passively absorbed or membrane integrity was affected as suggested by lack of caffeine absorption.