Neurochemical and Behavior Deficits in Rats with Iron and Rotenone Co-treatment: Role of Redox Imbalance and Neuroprotection by Biochanin A

Abstract

Increasing evidences show that the etiology of Parkinson's disease (PD) is multifactorial. Studying the combined effect of several factors is becoming a hot topic in PD research. On one hand, iron is one of the essential trace metals for human body; on the other hand, iron may be involved in the etiopathogenesis of PD. In our present study, the rats with increased neonatal iron (120 μg/g bodyweight) supplementation were treated with rotenone (0.5 mg/kg) when they were aged to 14 weeks. We observed that iron and rotenone co-treatment induced significant behavior deficits (time-dependent) and striatal dopamine depletion in the male and female rats, while they did not do so when they were used alone. No significant change in striatal 5-hydroxytryptamine content was observed in the male and female rats with iron and rotenone co-treatment. Also, iron and rotenone co-treatment significantly decreased substantia nigra TH expression in the male rats. Furthermore, co-treatment with iron and rotenone significantly induced malondialdehyde increase and glutathione decrease in the substantia nigra of male and female rats. There was no significant change in cerebellar malondialdehyde and glutathione content of the rats co-treated with iron and rotenone. Interestingly, biochanin A significantly attenuated striatal dopamine depletion and improved behavior deficits (dose-dependently) in the male and female rats with iron and rotenone co-treatment. Biochanin A treatment also significantly alleviated substantia nigra TH expression reduction in the male rats co-treated with iron and rotenone. Finally, biochanin A significantly decreased malondialdehyde content and increased glutathione content in the substantia nigra of male and female rats with iron and rotenone co-treatment. Our results indicate that iron and rotenone co-treatment may result in aggravated neurochemical and behavior deficits through inducing redox imbalance and increased neonatal iron supplementation may participate in the etiopathogenesis of PD. Moreover, biochanin A may exert dopaminergic neuroprotection by maintaining redox balance.

Neurobehavioral and neuroprotective role of captopril in the rotenone model of rat Parkinsonism

“…This may be attributed to neuroprotection and less severe damage to dopaminergic neurons among these rats. Similar improvement in dopamine levels postulated to be due to neuroprotective effects of test drugs has been reported after administration of biochanin A (Yu et al, 2017) (in MPTP model), adenosine A receptor blockers (Fathalla et al, 2016) (rotenone model) and catechin (Teixeira et al, 2013) (6-OHDA model). There are many reports concentrating on the dopamine levels in the speci ic regions of the brain and has shown that co-administration of artemisi (Pal and Ghosh, 2018), Juniperus (Bais et al, 2015) and much Chinese herbal preparation (Kum et al, 2011;Pan et al, 2011) resulted in improved dopamine levels.…”

Idebenone Alleviates Neuroinflammation and Modulates Microglial Polarization in LPS-Stimulated BV2 Cells and MPTP-Induced Parkinson’s Disease Mice

“…The levels of dopamine and its metabolites (DOPAC) in the striatum were measured using an HPLC apparatus (Yu et al, 2017). Briefly, the striatum was weighed and quickly removed on ice.…”

Behavioral Tests in Neurotoxin-Induced Animal Models of Parkinson’s Disease

“…They tested the co-administration of iron (120 µg/g, intraperitoneally) with rotenone consecutively for 35 days and tested behavioral parameters at 14 weeks. Their cotreated iron plus rotenone group showed worse neurochemical and motor deficits in male and female rats [ 190 ]. Zhang et al (2017) administered rotenone at the dose of 1.5, 2, or 2.5 mg/kg/day for five weeks (in sunflower oil) in male Wistar rats.…”