Amelioration of hearing loss by long-term omega-3 supplementation involves homocysteine metabolism

Abstract

[Background]: Beneficial effects of omega-3 (w3) polyunsaturated fatty acids (PUFAs) in cognitive function, inflammation and oxidative stress have been described. Additionally, an association between hearing loss and low plasmatic levels of PUFAs and serum folate, as well as high total homocysteine (tHcy) has been reported. [Objective]: The evaluation of the potential effects of long-term w3-supplementation in prevention and/or delay of the onset of hearing loss. [Design]: Two-month-old C57BL/6J mice were fed control or w3-supplemented diets for 8 months. A set of 4 month-old control mice was used for comparative purposes. [Results]: Auditory brainstem response (ABR) thresholds in control mice increased with age, whereas distortion product otoacustic emissions (DPOAE) thresholds showed lower amplitudes in mid-high frequencies. These changes in hearing parameters were partially ameliorated by long-term w3-supplementation. No gross histological differences were detected between control and w3 cochleae by Cresyl violet staining and immunohistochemistry, neither significant changes in tHcy or serum folate levels were measured by HPLC and microbiological methods, respectively. Ageing in the control group was associated with imbalanced cochlear cytokine expression toward increased pro-inflammatory cytokines as determined by RT-qPCR, an effect prevented by w3-supplementation. Decreased expression of most genes of cochlear Hcy metabolism was shown during aging of the control group, but only alterations in Bhmt and Cbs were significantly precluded by w3-feeding. However, changes in protein levels by western blotting indicated increased cystathione b-synthase levels in the 10 month-old controls that were prevented by w3, although increasing betaine homocysteine methyltransferase protein. Moreover, no significant variations in global homocysteinylation levels were detected by western blotting between groups. [Conclusions]: Ageing induces inflammation and hearing loss together with increased transsulfuration in control mice. Long-term w3-supplementation improved signs of inflammation and hearing loss, simultaneously promoting Hcy remethylation and reducing transulfuration.