Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Neuroprotective effect of insulin-like growth factor-II on 1-methyl-4-phenyl pyridinium-Induced oxidative damage in cortical neuronal cells

Wei Dong¹, Li Hu², Xiao-Wei Xu³

For correspondence:- Xiao-Wei Xu Email: meili77072@gmail.com Tel:+0865373412259

Received: 6 June 2014 Accepted: 8 April 2015 Published: 29 July 2015

Citation: Dong W, Hu L, Xu X. Neuroprotective effect of insulin-like growth factor-II on 1-methyl-4-phenyl pyridinium-Induced oxidative damage in cortical neuronal cells. Trop J Pharm Res 2015; 14(7):1191-1197 doi: 10.4314/tjpr.v14i7.10

© 2015 The authors.
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Abstract

Purpose: To evaluate the receptor-mediated neuroprotective effect of insulin-like growth factor-II (IGF-II) on 1-methyl-4-phenyl pyridinium (MPP)-induced oxidative damage in adult cortical neuronal cultures.

Methods: Adult rats were randomly divided into 5 groups. Cortical neurons were prepared from rats. The cells were exposed to 10 μM of MPP (group 1, G1); MPP + 100 ng/mL of IGF-II (group 2, G2); MPP + IGF in the presence of 20 ng/μL IGF-I analogue (group 3; G3); 5 ng/μL anti-IGF-IIR (group 4; G4); or MPP + IGF II + IGF inhibitor (group 5; G5). The level of reactive oxygen species (ROS), levels of oxidative stress markers, antioxidant enzymes, mitochondrial functional markers were analyzed in the MPP-treated neuronal cells (with or without treatment with IGF-II).

Results: The results demonstrate that IGF-II treatment protects MPP-induced toxicity by decreasing ROS production (58.33 %; p F6; 0.001), AChE levels (50 %), and maintaining the innate antioxidants to near normal levels. The study on oxidative functional markers showed that IGF-II significantly decreased the MPP-induced elevated levels and mitochondrial markers (TBARS, 40 %, LOOH-39.28 %) to near normal levels. Further analysis using inhibitors of IGF-IR (IGF-I analogue) and IGF-IIR (anti-IGF-IIR) showed that involvement of IGF-IIR might have greatly contributed to the neuroprotective effect of IGF-II.

Conclusion: IGF-II receptors play a significant role in the neuroprotective mechanism of IGF-II by acting as an antioxidant, thereby reducing the neuro-degeneration induced by oxidative insults. This indicates that IGF-II receptors are a potential target for the treatment of diseases related to imbalance in redox homeostasis.

Keywords: Insulin-like growth factor-II, Neuronal cells, 1-Methyl-4-phenyl pyridinium, Mitochondrial markers, Oxidative stress, Neuroprotection, Antioxidant