Linezolid Inhibited Synthesis of ATP in Mitochondria: Based on GC-MS Metabolomics and HPLC Method

Abstract EN

Linezolid has been widely used in serious infections for its effective inhibiting effect against multidrug-resistant gram-positive pathogens.

However, linezolid caused severe adverse reactions, such as thrombocytopenia, anaemia, optic neuropathy, and near-fatal serotonin syndrome.

In order to investigate the toxicity of linezolid, twenty-four Sprague-Dawley rats were randomly divided into: control group (n=7), low-group (n=8), and high-group (n=9).

The rats of low-group and high-group were given by gavage with linezolid 60 and 120 mg/kg/day for 7 days, respectively.

The serum concentration of linezolid was determined by high performance liquid chromatography (HPLC); blood metabolic change was analyzed by gas chromatography-mass spectrometer (GC-MS).

Adenosine triphosphate (ATP) concentration in HepG2-C3A after being cultured with linezolid was determined by HPLC.

The results showed that there were six metabolites and nine metabolites had statistical differences in low-group and high-group (P<0.05).

The trimethyl phosphate was the most significant indicator in those changed metabolites.

Except for d-glucose which was slightly increased in low-group, octadecanoic acid, cholest-5-ene, hexadecanoic acid, α-linolenic acid, eicosapentaenoic acid, 9,12-Octadecadienoic acid, and docosahexaenoic acid were all decreased in low-group and high-group.

ATP concentration was decreased in HepG2-C3A after cultured with linezolid.

In conclusion, the toxicity of linezolid is related to its serum concentration.

Linezolid may inhibit the synthesis of ATP and fatty acid.