The cannabinoid receptor 2 agonist JWH-133 is capable of revoking changes in cochlear microcirculation induced by lipopolysaccharide

Introduction:

Cannabinoid receptors (CBR) are divided into two subclasses. The subtype 2 mediates several antiinflammatory effects that make it a valid candidate as an otoprotective agent. We therefore investigated the ability of JWH-133, a CBR-2 agonist, to reduce the effects of abacterial labyrinthitis on cochlear microcirculation.

Material and Methods:

40 dunkin-hartley guines pigs were divided into 8 groups of 5 animals each. In each animal cochlear microcirculation was quantified by in-vivo fluorescence microscopy. In the first four groups, lipopolysaccharide (LPS) was applied topically in various concentration (1 mg/ml, 10 µg/ml, 100 ng/ml, placebo) to emulate the effects of abacterial labyrinthitis. In the second four groups, JWH-133 (500 ng/ml), a potent CBR-2 agonist, was applied topically before application of LPS. Microcirculation was quantified before, 30 minutes after the initial treatment and at the end of the second treatment.

Results:

30 and 60 minutes after topical application of LPS, microcirculation dropped to 79.1% or 75.6%, respectively (1 mg/ml), to 88.8% or 81.7%, respectively (10 µg/ml) and to 96.8% or 89.3%, respectively (100 ng/ml). Application of Placebo caused no such decreases in microcirculation (99.8% and 99.6% from the basal values). Previous application of JWH-133 showed no changes in microcirculation (97.8% of the basal values). The subsequent application of LPS then caused no changes in microcirculation (99.0% of the basal values).

Conclusion:

JWH-133 is capable of abrogating the effects of abacterial labyrinthitis on cochlear microcirculation. It therefore is a valid candidate as an otoprotective agent in bacterial otitis media and various other inner ear pathologies.

Publication History

Publication Date:
18 April 2018 (online)