Hyperhomocysteinemia induces matrix disruption and oxidative stress in inner ear

Abstract

Increasing number of clinical data suggests lower folic acid (FA) and high homocysteine (Hcy) causing hearing impairment. We analyzed hyperhomocysteinemia (HHcy) related matrix remodeling, oxidative stress and blood flow which may contribute to impaired hearing. We used wild type (WT) and heterozygous Cystathione beta‐synthase (CBS) mice. CBS () has higher level of plasma Hcy and exhibits some pathological features of HHcy. Expression of matrix metalloprotease (MMPs), their inhibitors, the TIMPs and nitrotyrosine (NT), p22phox and NOX‐3 were analyzed by western blotting and RT‐PCR. Masson Trichrome staining was done for collagen. Western blot analyses revealed increased level of active MMP‐2, MMP‐14 protein in CBS () mice. MMP‐9, MMP‐12 and MMP‐13 mRNA were higher in CBS () than the WT. Nitrotyrosine and p22phox was higher in CBS (), whereas NOX‐3 level showed moderate increase in CBS () as compared to WT. Staining for collagen was higher in WT as compared to CBS (). Hair cells were disorganized in CBS () along with hypertrophy as compared to WT. Our data suggested increased disruption of intercellular matrix resulting in damage and disorganized cellular structure in cochlea. Moreover an increased level of oxidative stress may also contribute to impaired hearing threshold.