Betahistine alleviates benign paroxysmal positional vertigo (BPPV) through inducing production of multiple CTRP family members and activating the ERK1/2-AKT/PPARy pathway

BACKGROUND: Betahistine is a clinical medication for the treatment of benign paroxysmal positional vertigo (BPPV). Otolin, a secreted glycoprotein with a C-terminal globular domain homologous to the immune complement C1q, has been identified as a biomarker for BPPV. However, the role of complement C1q/TNF-related proteins (CTRPs) with a C-terminal globular domain in BPPV is unclear, so we explored the change of CTRPs in betahistine treated BPPV. METHODS: We treated BPPV patients with Betahistine (12 mg/time, 3 times/day) for 4 weeks and observed the clinical efficacy and the expression of CTRP family members in BPPV patients. Then, we constructed a vertigo mice model of vestibular dysfunction with gentamicin (150 mg/Kg) and a BPPV model of Slc26a4loop/loop mutant mice. Adenoviral vectors for CTRP expression vector and small interfering RNA were injected via the intratympanic injection into mice and detected the expression of CTRP family members, phosphorylation levels of ERK and AKT and the expression of PPARγ. In addition, we treated mice of vestibular dysfunction with Betahistine (10 mg/Kg) and/or ERK inhibitor of SCH772984 (12 mg/Kg) and/or and PPARγ antagonist GW9662 (1 mg/Kg) for 15 days, and evaluated the accuracy of air righting reflex, the time of contact righting reflex and the scores of head tilt and swimming behavior. RESULTS: After treatment with Betahistine, the residual dizziness duration and the score of the evaluation were reduced, and the expression of CTRP1, 3, 6, 9 and 12 were significantly increased in BPPV patients. We also found that Betahistine improved the accuracy of air righting reflex, reduced the time of contact righting reflex and the scores of head tilt and swimming behavior in gentamicin-treated mice and Slc26a4loop/loop mutant mice. The expression levels of CTRP1, 3, 6, 9 and 12, phosphorylation levels of ERK and AKT, and PPARγ expression were significantly increased, and the scores of head tilt and swimming behavior were decreased in vestibular dysfunction mice with overexpression of CTRPs. Silencing CTRPs has the opposite effect. SCH772984 reversed the effect of Betahistine in mice with vestibular dysfunction. CONCLUSION: Betahistine alleviates BPPV through inducing production of multiple CTRP family members and activating the ERK1/2-AKT/PPARy pathway.

Revisión de los medicamentos antivertiginosos / a review of antivertigo medication

Objetivo. Valorar la información existente sobre los efectos de las sustancias antivertiginosas, basados en la bibliografía asequible. Información. Se localizaron artículos pertinentes en Medline y en revistas obtenidas en la ciudad de México. Selección del material. Los artículos se seleccionaron en base a su aparente consistencia interna y su relación con el propósito de la revisión. Conclusión. Se evaluaron 22 substancias pertenecientes a 8 grupos farmacológicos (colinérgicos, antihistamínicos, GABAérgicos, bloqueadores de canales de calcio, serotoninérgicos, hemorreológicos, antiagregantes plaquetarios y diuréticos) útiles en diversos padecimientos vertiginosos. Se advirtió la necesidad de un método objetivo y cuantitativo para valorar resultados de ensayos clínicos en humanos. Mientra esto no ocurra, tendremos que usar los medicamentos en base de una información veraz, confiable y basada sólidamente en la farmacología estudiada en experimentos con animales y en la valoración cuidadosa de los efectos -buenos y malos- observados en nuestros pacientes.