5-LIPOXYGENASE INHIBITOR (ZILEUTON) PRODUCES ANTI-DEPRESSION EFFECT IN STRESS INDUCE CRS MICE MODEL

SAPTARSHI PANIGRAHI; SOMNATH SURAI; HAO HONG

doi:10.22159/ajpcr.2020.v13i2.36501

Authors

SAPTARSHI PANIGRAHI Department of Pharmacology, Key Laboratory of Neuropsychiatric Diseases, China Pharmaceutical University, Nanjing 210009, China.
SOMNATH SURAI Department of Pharmaceutics, Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
HAO HONG Department of Pharmacology, Key Laboratory of Neuropsychiatric Diseases, China Pharmaceutical University, Nanjing 210009, China.

DOI:

https://doi.org/10.22159/ajpcr.2020.v13i2.36501

Keywords:

Depression, Zileuton, 5-lipoxygenase, Neuroinflammation, Apoptosis

Abstract

Objective: The experiment aimed to find out the effectiveness of Zileuton, a 5-LOX inhibitor on depressive behavior and neuroinflammation in vivo.

Method: Male ICR mice (25-30g) randomly distributed Veh+Veh, CRS+Vehicle, CRS+ZIL50, and CRS+ZIL100. Zileuton was orally given in the treatment groups for 21 days after 3 weeks of stress induce CRS model. Starting from the day 1, in CRS model, mice were immobilized 8 hr/day for consecutive 21 days to induce stress. After completing the drug administration, subjected the mice for behavioral tests, and then performed histopathological and Western Blotting.

Result: Stress induces CRS model guide to the significant depressive-like behavior of the mice in behavioral tests which was united by adverse changes at the cellular/molecular level responsible for regulation of inflammatory and apoptotic processes. CRS triggered Microglial over activation in the DG of the hippocampus, which was successfully inhibited by Zileuton post-treatment at the dose of 100mg/kg than 50mg/kg. Level of TNF-α, IL- 1β, nuclear NF-κB p65, Bax, and cleaved Caspase-3 was high and Bcl-2 expression was low in the stress induce CRS -treated mice which were found to be opposite in the Zileuton (100mg/kg). However, the dose of 50mg/kg less to mimic the effects as exhibited more by the 100mg/kg dose of Zileuton.

Conclusion: It can be concluded that selective 5-lipoxygenase inhibitor Zileuton can efficiently inhibit the depressive-like behavior/activity in CRS-induced depressive mouse model. The study is the first to show the role of 5-lipoxygenase enzyme in and Chronic Restraint Stress (CRS)-induced mice models of stress, anxiety or depression.

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