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

Haj-Mirzaian, A and Ramezanzadeh, K and Tafazolimoghadam, A and Kazemi, K and Nikbakhsh, R and Amini-Khoei, H and Afshari, K and Haddadi, N and Shakiba, S and Azimirad, F and Mousavi, S and Dehpour, A (2019) Protective effect of minocycline on LPS-induced mitochondrial dysfunction and decreased seizure threshold through nitric oxide pathway. European Journal of Pharmacology, 858.

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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

Item Type: Article
Uncontrolled Keywords: LPS, Minocycline, Mitochond, rial dysfunction, Nitric oxidePro-inflammatory cytokines, Seizure
Subjects: QT physiology
WB Practice of Medicine
QU Biochemistry
QV pharmacology
Divisions: Faculty of Medicine
Depositing User: Unnamed user with email nazari@skums.ac.ir
Date Deposited: 01 Jul 2019 03:35
Last Modified: 01 Jul 2019 03:36
URI: http://eprints.skums.ac.ir/id/eprint/7790

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