Mechanistic investigation of 4-aminobenzoic acid hydrazide, a myeloperoxidase inhibitor for alleviating oxidative stress, neuroinflammation and functional disabilities in a rat model of traumatic brain injury

Background/Objective

Myeloperoxidase (MPO) is a key enzyme secreted from neutrophil azurophilic granules in traumatic brain injury (TBI). 4-Aminobenzoic acid hydrazide (4ABAH) inhibits MPO irreversibly. This study examines 4ABAH's effect on weight drop-induced TBI in rats.

Methods

4ABAH (40 mg/kg, b.i.d., i.p.) post-treatment for one (acute) and five days (repeated) was evaluated against weight drop-induced TBI in Sprague-Dawley rats. In addition to the histopathological and behavioural studies (beam walking test, rearing test, actophotometer and Y-Maze test), biochemical makers such as brain oedema, MPO activity, malondialdehyde, nitrite, catalase, and reduced glutathione levels in brain tissue were also estimated.

Results

The findings demonstrated that locomotor function and short-term memory of rats were impaired one day and five days after TBI. The findings also revealed increased brain oedema, MPO activity, malondialdehyde, and nitrite levels, as well as decreased catalase and glutathione levels in rats subjected to trauma. Acute post-treatment with 4ABAH mitigated TBI-induced alteration of locomotor activity in the beam walking test and cylinder test as well as malondialdehyde, nitrite, and reduced glutathione levels in the brain of the rats. However, acute treatment did not alleviate TBI-induced brain oedema, altered histological examinations, MPO activity, catalase levels, and rats' performance in the actophotometer or Y-maze. On the other hand, repeated post-treatment with 4ABAH ameliorated the histopathological, neurochemical, and behavioural consequences of trauma.

Conclusion

Traumatised animals recovered partially after acute 4ABAH post-treatment; however, repeated post-treatment improved trauma outcomes significantly. Therefore, MPO may be a promising therapeutic target for TBI therapy.