Therapeutic effect of apocynin through antioxidant activity and suppression of apoptosis and inflammation after spinal cord injury

Abstract

Spinal cord injury (SCI) is a devastating condition affecting hundreds of thousands of people worldwide annually. SCI results in activation of the inflammatory response and apoptosis, and generates oxidative stress, which has deleterious effects on the recovery of motor function. Apocynin, an inhibitor of NADPH oxidase, has been demonstrated to improve neuronal functional recovery in rat models of SCI. However, the efficacy of apocynin treatment post-SCI has not been investigated. The aim of this study was to observe the effects of apocynin on the repair of acute spinal cord damage in rats and to examine the potential beneficial effects. A rat model of SCI was established, and apocynin (50 mg/kg) was administered intraperitoneally at 30 min after SCI and then every 12 h for 3 days. In order to examine oxidative tissue injury, the levels of malondialdehyde and glutathione and activities of myeloperoxidase and superoxide dismutase in the spinal cord tissues were measured. Histological evaluations were also conducted. NeuN labeling, TUNEL staining and caspase 3 immunohistochemical staining were performed to analyze neuronal damage and apoptosis around the lesion. Immunohistochemical analysis was also carried out to observe the expression of CD11b and glial fibrillary acidic protein. The expression levels of bax, bcl-2, tumor necrosis-α, interleukin (IL)-1β and IL-6 in the spinal cord tissue were assayed by western blotting. Finally, locomotor function was evaluated using the inclined plane test and Basso, Beattie and Bresnahan scores. The results showed that treatment with apocynin decreased oxidative damage, alleviated neuronal apoptosis, inhibited the inflammatory response and resulted in the promotion of locomotor function. Therefore, this study confirmed the therapeutic efficacy of apocynin in the repair of SCI, which was probably mediated via the inhibition of apoptosis and the inflammatory response, thus promoting the restoration of nerve function.

Inhibition of NADPH oxidase alleviates germ cell apoptosis and ER stress during testicular ischemia reperfusion injury

“…The dosage and i.p. administration of apocynin (50 mg/kg) were selected based on earlier studies using the same drug to investigate cerebral IRI ( Zhang et al 2015 ), striatum neurotoxicity ( Dang et al 2016 ) and spinal cord injury ( Sun et al 2017 ). The timing of apocycin injection during tIRI was decided based on the acute nature of the injury and its relation to the clinical settings of TTD.…”

The Lipoxin A4 Receptor Agonist BML-111 Alleviates Inflammatory Injury and Oxidative Stress in Spinal Cord Injury

“…Neuronal apoptosis results from inflammation, and oxidative stress can induce ASCI [5,6]. Inhibition of inflammatory response and oxidative stress during secondary injury is beneficial to recovery of motor function in ASCI rats [7]. Lipoxin is an endogenous anti-inflammatory lipid medium, which is only synthesized in a small amount under physiological conditions and is significantly increased under pathological conditions such as inflammatory injury to promote the regression of inflammation [8][9][10][11].…”

Reactive Oxygen Species from NADPH Oxidase and Mitochondria Participate in the Proliferation of Aortic Smooth Muscle Cells from a Model of Metabolic Syndrome

“…In addition to its wide use as an inhibitor of NADPH oxidase, DPI has been reported to inhibit other important enzymes such as NADPH ubiquinone oxidoreductase, nitric oxide synthase, xanthine oxidase, NADPH cytochrome P450 oxidoreductase, and cholinesterase that may be involved in cell survival [34]. Apocynin however is a specific inhibitor of NADPH oxidase [35]. It acts more specifically by inhibiting the association of p47phox and of p67phox with gp91phox as NADPH oxidase subunits, without affecting other proteins that may be vital for cell survival [36, 37].…”