Inducible nitric oxide inhibitor aminoguanidine, ameliorated oxidative stress, interleukin-6 concentration and improved brain-derived neurotrophic factor in the brain tissues of neonates born from titanium dioxide nanoparticles exposed rats

Abstract

Introduction: An interaction between oxidative stress, neuroinflammation, and nitric oxide (NO) has been suggested to have a role neurotoxicity. The aim of current research was to investigate the effect of aminoguanidine (AG) as an inducible NO synthase (iNOS) inhibitor, on brain-derived neurotrophic factor (BDNF), oxidative stress, and interleukin-6 (IL-6) concentrations in the brain tissues of neonates born from the rats exposed to titanium dioxide nanoparticles (TiO2 NPs) during gestation.

Methods: The pregnant rats were grouped into three and received: (1) saline, (2) TiO2 (200 mg/kg, gavage), and (3) TiO2-AG [200 mg/kg intraperitoneal (IP)]. The treatment was started since the second gestation day up to the delivery time. The neonates born from the rats were deeply anesthetized, sacrificed, and the brains were collected for biochemical evaluations.

Results: The neonates born from the rats exposed to TiO₂ showed a lower BDNF (p < .001) but a higher IL-6 (p < .01) concentrations in their hippocampal tissue. TiO₂ exposure also increased malondialdehyde (MDA) (p < .001) and NO metabolites (p < .001), while diminished thiol (p < .001), superoxide (SOD) (p < .001), and catalase (CAT) (p < .001) in all hippocampal, cortical, and cerebellar tissues. Administration of AG improved BDNF (p < .01) but attenuated IL-6 (p < .01) concentrations in the hippocampal tissue. AG also decreased MDA (p < .001) and NO metabolites (p < .01–p < .001), while increased thiol (p < .01–p < .001), SOD (p < .001), and CAT (p < .05–p < .001) in all cerebellar, hippocampal, cortical, and tissues.

Conclusion: The results of the current research revealed that iNOS inhibitor AG, ameliorated oxidative stress, IL-6 concentration, and improved BDNF in the brain tissues of neonates born from TiO₂ NPs exposed rats.

Keywords:

• Aminoguanidine
• brain-derived neurotrophic factor
• inducible nitric oxide
• interleukin-6
• neonates
• titanium dioxide

Acknowledgments

The results described in this paper were from an MSc student’s thesis. The authors would like to thank the Vice Presidency of Research of Mashhad University of Medical Sciences for their financial support.

Disclosure statement

No potential conflict of interest was reported by the authors.