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Puromycin-induced lipid peroxidation in the cochlea of ApoE knockout mice
A A Aarnisalo1, K Aalto-Setälä, H Holthöfer
1Department of Otolaryngology, HUCH, Helsinki, Finland.
Abstract:
Puromycin-treated apolipoprotein E (ApoE)-deficient mice were used to study lipid peroxidation (LPO) in the cochlea. Puromycin causes accelerated peroxidation of lipids and induces both inner ear and renal lesions in experimental animals presenting with abnormally high serum cholesterol. To prevent LPO, we used probucol, an effective inhibitor of LPO, and, simultaneously, also a lipid-lowering drug. The mice were given a single injection of the aminonucleoside of puromycin (25 mg/100 g). Polyclonal malondialdehyde and 4-hydroxynonenal antibodies were used to localize the LPO products. LPO products were mainly found in the stria vascularis of puromycin-treated mice. No LPO products were observed in the hair cells. LPO product immunoreactivity was clearly diminished in the animal group treated with both puromycin and probucol. In the cochlea of the ApoE-deficient mouse, puromycin affects mainly the stria vascularis due to the accelerated peroxidation of structural lipids. Probucol treatment prevented the formation of LPO products.
Insights
Puromycin induces lipid peroxidation in the inner ear of ApoE-deficient mice, primarily affecting the stria vascularis. Probucol, an LPO inhibitor, effectively prevented these cochlear lesions.
Area of Science:
- Otorhinolaryngology
- Biochemistry
- Pharmacology
Background:
- Apolipoprotein E (ApoE)-deficient mice exhibit high serum cholesterol, predisposing them to lipid peroxidation (LPO).
- Puromycin administration accelerates lipid peroxidation, leading to inner ear and renal damage in experimental models.
- The stria vascularis is a critical cochlear structure involved in maintaining the endolymph ionic environment.
Purpose of the Study:
- To investigate the effects of puromycin-induced lipid peroxidation in the cochlea of ApoE-deficient mice.
- To evaluate the protective role of probucol, an LPO inhibitor and lipid-lowering agent, against cochlear damage.
Main Methods:
- ApoE-deficient mice were treated with puromycin to induce LPO.
- Immunohistochemistry using malondialdehyde and 4-hydroxynonenal antibodies localized LPO products.
- Mice were co-treated with puromycin and probucol to assess probucol's efficacy.
Main Results:
- Puromycin treatment resulted in significant LPO product accumulation in the stria vascularis of the cochlea.
- No LPO products were detected in cochlear hair cells.
- Co-administration of probucol markedly reduced LPO product immunoreactivity in the cochlea.
Conclusions:
- Puromycin induces lipid peroxidation in the stria vascularis of ApoE-deficient mice, impacting cochlear structure.
- Probucol effectively inhibits puromycin-induced LPO and prevents cochlear damage in this model.
- These findings highlight the role of LPO in cochlear pathology and the therapeutic potential of probucol.