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Protective effect of minocycline on LPS-induced mitochondrial dysfunction and decreased seizure threshold through nitric oxide pathway.

Abstract：

:Lipopolysaccharide (LPS) increases inflammatory cytokines of the brain and deregulates the mitochondrial function, thus could increase the seizure susceptibility. Studies have shown that minocycline has neuroprotective and antioxidant properties. In this study, we aimed to evaluate the anticonvulsant properties of minocycline in LPS-treated animals and the possible involvement of nitric oxide and mitochondrial pathways. In a PTZ model of seizure in mice, minocycline was administrated to LPS-treated mice. Then followed by co-injection of its sub-effective dose and NOS inhibitors including 7-Nitroindazole (7-NI), aminoguanidine (AG) and L-NG-Nitroarginine methyl ester (L-NAME) to evaluate the changes in seizure threshold and the possible involvement of nitrergic system. Molecular assessments were used to evaluate the effects of each treatment on inflammation and mitochondrial function in the brain. LPS-treated animals had lower seizure threshold compared to intact animals; injection of minocycline (80 mg/kg) to LPS-treated mice reversed this effect. Co-injection of sub-effective doses of minocycline (40 mg/kg) and L-NAME to LPS-treated animals significantly increased seizure threshold. We observed that co-treatment of minocycline and AG dissimilar to 7-NI could increase the seizure threshold of LPS-treated animals. L-arginine reversed the anticonvulsant effect of minocycline. Also, molecular evaluations showed that LPS could increase the ATP levels, GSH levels, and reactive oxygen species formation. However, minocycline at both doses significantly reversed the effect of LPS. Minocycline counteracts the proconvulsant effects of LPS through regulating of mitochondrial function and decreasing of neuro-inflammation. Also, co-administration of minocycline and i-NOS inhibitors could intensify anticonvulsant effects of minocycline.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Haj-Mirzaian A,Ramezanzadeh K,Tafazolimoghadam A,Kazemi K,Nikbakhsh R,Nikbakhsh R,Amini-Khoei H,Afshari K,Haddadi NS,Shakiba S,Azimirad F,Mousavi SE,Dehpour AR

doi

10.1016/j.ejphar.2019.172446

subject

Has Abstract

pub_date

2019-09-05 00:00:00

pages

172446

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(19)30398-X

journal_volume

858

pub_type

杂志文章

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Protective effect of minocycline on LPS-induced mitochondrial dysfunction and decreased seizure threshold through nitric oxide pathway.