Maintenance of iron homeostasis by apocynin during states of global ischemia in rat brain and retina

Abstract

Ischemic stroke is associated with several neurodegenerative factors, which are exacerbated further during reperfusion. Increased iron storage in the brain also contributes to stroke progression and worsens the outcome with the induction of oxidative stress and inflammation. Further, several clinical studies have demonstrated that disease susceptibility, response to infection and inflammation, worsen with increased iron levels. So, in the present study, the iron levels were assessed using atomic absorption spectroscopy and Prussian blue staining in the brain and retina of the rats post ischemic insult. The retinal alterations were also assessed as retina is a projection of the CNS. The expressions of the regulatory genes of iron homeostasis were estimated in the cerebrum. In addition to it, the BBB disruption due to iron overload and oxidative stress, were measured. The iron levels were found to be significantly higher in the cortical and hippocampal regions leading to the appearance of iron deposits and cellular damage in retina post ischemic injury. In the current study the protective role of apocynin, a NADPH oxidase assembly inhibitor, was assessed against the alterations induced by disturbed iron homeostasis post cerebral ischemia. Apocynin supplementation was able to maintain the iron homeostasis in the brains of ischemic rats through the normalization of the gene expressions of regulatory genes and restoration of the BBB integrity. The decline in the iron levels in the brain after apocynin supplementation also prevented the appearance of iron deposits and cellular damage in the retina during the states of cerebral ischemia.

Keywords

• Iron
• Ferritin
• Retina
• Apocynin
• Hypoxia inducible factor-1
• Ischemia