Vernonia amygdalina displays otoprotective effects via antioxidant pathway on cisplatin-induced hair cell loss in zebrafish.

Abstract

Iatrogenic hearing loss is defined as irreversible cochlear hair cell injury resulting from medical intervention, such as cisplatin, which leads to the overproduction of reactive oxygen species (ROS). Vernonia amygdalina (VA), a medicinal herb, has recently been found to exerted pharmacotherapeutic potential due to its antioxidant activity. In the present study, we used a transgenic zebrafish line (pvalb3b: TagGFP) as an in vivo screening platform for discovering compounds or agents with potential otoprotective ability and a combination of behavioral methods for assessing the physiological outcome. The 1 h of 250 μM cisplatin treatment induced severs injury to lateral-line hair cell that triggered a drastic cell death response. Five readouts were conducted as the parameters of VA ultrasonic water extract (VAUWE) protection against cisplatin ototoxicity: (1) radical-scavenging ability, (2) hair cell viability, (3) mechanotransduction (MET) channel functionality, (4) apoptosis, (5) antioxidant defense, and (6) locomotor behavior. Our results demonstrated that 1-h pretreatment of VAUWE with non-toxic concentrations (1.0 mg/ml and 2.0 mg/ml) increases hair cell viability by blocking cisplatin entry through the MET channel and subsequently ameliorates apoptotic cell death. Regarding molecular mechanisms, VAUWE also modulates the expression of antioxidant enzyme gene, which collectively contributes to restoring impaired swimming behavior induced by cisplatin ototoxicity. The findings of the present study might highlight the in vivo protective role of VAUWE on modulating cisplatin-induced hair cell damage in transgenic zebrafish, which further informs preclinical foundations for developing potential otoprotectants against iatrogenic hearing loss.