Cytotoxic effects of dimethyl sulphoxide (DMSO) on cochlear organotypic cultures

• Published in: Hearing research 2008-02, Vol.236 (1), p.52-60
• Main Authors: Qi, Weidong, Ding, Dalian, Salvi, Richard J.
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; Biological and medical sciences; Caspase-8; Caspase-9; Caspases - metabolism; Cell Nucleus - drug effects; Cell Nucleus - pathology; Cochlea - drug effects; Cochlea - enzymology; Cochlea - pathology; Cochlear organotypic culture; Dimethyl Sulfoxide - administration & dosage; Dimethyl Sulfoxide - toxicity; Dimethyl sulphoxide; Dose-Response Relationship, Drug; Drug toxicity and drugs side effects treatment; Hair cells; Hair Cells, Auditory, Inner - drug effects; Hair Cells, Auditory, Inner - enzymology; Hair Cells, Auditory, Inner - pathology; Hair Cells, Auditory, Outer - drug effects; Hair Cells, Auditory, Outer - enzymology; Hair Cells, Auditory, Outer - pathology; Medical sciences; Mitochondria; Organ Culture Techniques; Pharmacology. Drug treatments; Rats; Rats, Inbred F344; Solvents - administration & dosage; Solvents - toxicity; Toxicity: respiratory system, ent, stomatology; TUNEL
• ISSN: 0378-5955; 1878-5891
• DOI: 10.1016/j.heares.2007.12.002

The amphipathic molecule dimethyl sulphoxide (DMSO) is a solvent often used to dissolve compounds applied to the inner ear; however, little is known about its potential cytotoxic side effects. To address this question, we applied 0.1–6% DMSO for 24 h to cochlear organotypic cultures from postnatal day 3 rats and examined its cytotoxic effects. DMSO concentrations of 0.1% and 0.25% caused little or no damage. However, concentrations between 0.5% and 6% resulted in stereocilia damage, hair cell swelling and a dose-dependent loss of hair cells. Hair cell damage began in the basal turn of the cochlea and spread towards the apex with increasing concentration. Surprisingly, DMSO-induced damage was greater for inner hair cells than outer hair cell whereas nearby supporting cells were largely unaffected. Most hair cell death was associated with nuclear shrinkage and fragmentation, morphological features consistent with apoptosis. DMSO treatment induced TUNEL-positive staining in many hair cells and activated both initiator caspase-9 and caspase-8 and executioner caspase-3; this suggests that apoptosis is initiated by both intrinsic mitochondrial and extrinsic membrane cell death signaling pathways.