Effect Of L-carnitine On Mitochondrial DNA 4834bp Deletion In Rats And Its Relationship With Presbycusis

Objective:To investigate the effect of L-carnitine on the mt DNA 4834bp deletion in D-gal-induced aging rats and its relationship with presbycusis.Methods:One month old male SD rats?n=48?were randomly divided into four groups:Na Cl group?control group?,D-gal+Na Cl group?model group?,D-gal+LC group and Na Cl+LC group,with 12 rats in each group.The administration of each group was as follows:D-gal+Na Cl group,5%D-gal?150mg/kg/d?was subcutaneously injected into the neck,and 0.9%normal saline was intraperitoneally injected half an hour later;D-gal+LC group:5%D-gal?150mg/kg/d?was subcutaneously injected into the neck,and L-carnitine?100mg/kg/d?was intraperitoneally injected half an hour later;D-gal+Na Cl group;0.9%normal saline was subcutaneously injected into the neck,and L-carnitine?LC??100mg/kg/d?was injected intraperitoneally half an hour later;Na Cl group,0.9%normal saline was subcutaneously injected into the neck.Continuous administration for 8 weeks.Colorimetry method was used to detect MDA content,the SOD activity and H₂O₂concentration in serum and ventral cochlear nucleus.The level of NOX2 protein in ventral cochlear nucleus was detected by western blot,and the deletion rate of mt DNA 4834bp was detected by Quantitative Real-time PCR.Results:?1?Colorimetry results showed that,in the serum,compared with the other three groups,H₂O₂ concentration and MDA content were significantly increased?P<0.05?and SOD activity was significantly decreased in D-gal+Na Cl group?P<0.05?;compared with Na Cl group,MDA content were significantly increased?P<0.05?and SOD activity was significantly decreased in D-gal+LC group?P<0.05?;compared with Na Cl+LC group and Na Cl group,H₂O₂ concentration in D-gal+LC group was significantly increased?P<0.05?;In the ventral cochlear nucleus,H₂O₂ concentration and MDA content were significantly increased?P<0.05?and SOD activity was significantly decreased in D-gal+Na Cl group?P<0.05?;in D-gal+LC group,H₂O₂concentration was higher than that in Na Cl group,MDA content was higher than that in the Na Cl+LC group,and SOD activity was lower in D-gal+LC group.The results suggested that D-gal could increase reactive oxygen and induce oxidative stress in SD rats,and L-carnitine could significantly reduce the concentration of reactive oxygen and inhibit oxidative stress injury.?2?Western blot results showed that,compared with Na Cl+LC group and Na Cl group,the expression level of NOX2 in D-gal+Na Cl group was significantly increased?P<0.05?;compared with D-gal+Na Cl group,NOX2 level in D-gal+LC group was significantly reduced?P<0.05?;compared with D-gal+LC group,NOX2 level in Na Cl+LC group and Na Cl group was significantly reduced?P<0.05?.There was no significant difference between Na Cl+LC group and Na Cl group.These results suggest that L-carnitine could reduce the expression of NOX2 and inhibit the oxidative stress associated with NADPH oxidase.?3?Quantitative Real-time PCR results showed that,compared with Na Cl+LC group and Na Cl group,the deletion rate of mt DNA4834bp in D-gal+Na Cl group was significantly increased?P<0.05?;compared with D-gal+Na Cl group,the deletion rate of mt DNA4834bp in D-gal+LC group was significantly lower?P<0.05?;compared with D-gal+LC group,the deletion rate of mt DNA4834bp in Na Cl+LC group and Na Cl group was significantly decreased?P<0.05?.These results suggested that L-carnitine could significantly alleviate the oxidative damage of mitochondrial DNA and reduce mt DNA4834bp deletion in the ventral cochlear nucleus of D-gal-induced aging rats.Conclusion:L-carnitine could inhibit the deletion rate of mt DNA 4834bp in the cochlea of D-gal-induced aging rats,and delay the occurrence of presbycusis.