Role of 6-amino flavone in attenuating cisplatin induced neurotoxicity via inhibition of p-JNK signaling pathway in post-natal day-7 mice

Abstract

OBJECTIVE: To investigate the protective role of 6-amino flavone (6-AF) in cisplatin-induced neuro-inflammation in the developing brains of post-natal day-7 (PND-7) mice. METHODS: This experimental study, conducted at the Neuro Molecular Medicines Research Center in Peshawar, Pakistan, included 20 PND-7 mice from January to March 2023. PND-7 mice were randomly distributed into four groups, a control group, a cisplatin group, a cisplatin + 6-AF group, and a 6-AF group. Cisplatin was administered intraperitoneally at a dose of 20 mg/kg to the cisplatin group. 6-AF was injected at a dose of 30 mg/kg after cisplatin administration to cisplatin+6-AF group and 6-AF group mice. After 4 hours of the drug treatment, all the PND-7 mice were sacrificed for Western blot analysis. ImageJ software was used for the densitometry of the blots. One-way ANOVA and post-hoc Tukey tests through Prism Graph-5 were applied for statistical analysis. RESULTS: Significant differences in p-JNK levels along with TNF-α, NF-κB, and IL-1β proteins were observed in the brain homogenates of PND-7 mice in various groups. A post-hoc Tukey test revealed a significant increase (p<0.001) in the p-JNK, COX-2, NF-κB, and IL-1β levels in the cisplatin group as compared to control group mice. However, a significant decrease (p<0.001) was observed in p-JNK, COX-2, NF-κB, and IL-1β expression levels in the cisplatin + 6-AF group as compared to the cisplatin group. CONCLUSION: Administration of 6-AF effectively reduced cisplatin-induced neurotoxicity in PND-7 mice, demonstrating a neuroprotective effect by suppressing p-JNK and its downstream TNF-α, NF-κB, and IL-1β proteins.

Keywords

• cisplatin
• 6-amino flavone
• neuroinflammatory diseases
• p-jnk signaling pathway
• nf-κb
• tumor necrosis factor-alpha
• tnf-α