N-Acetylcysteine and Safranal prevented the brain damage induced by hyperthyroidism in adult male rats

ABSTRACT

Background: Hyperthyroidism is associated with impairment in the neurotransmission and severe tissue damage in the brain. The present study explored the potential deleterious effects of experimentally-induced hyperthyroidism on the neurotransmitters, oxidative homeostasis, apoptosis and DNA fragmentation in cerebral cortex, thalamus & hypothalamus, and hippocampus in rats.

Methods and Results: The ameliorative effects of N-acetylcysteine (NAC; 50 mg/kg, oral) and safranal (50 mg/kg, intraperitoneal) against hyperthyroidism (L-T4 500 µg/kg, subcutaneous) were investigated. All treatments continued daily over three weeks. Hyperthyroidism was manifested by significant elevations in serum fT3 and fT4 levels and a decline in serum TSH level and body weight. It was also characterized by significant elevations in the levels of dopamine, serotonin, and 5-hydroxyindole acetic acid, and monoamine oxidase activity to varying degrees in the brain regions examined and a significant reduction in norepinephrine in hippocampus only. Hyperthyroidism resulted in a significant oxidative stress in brain typified by elevations in malondialdehyde and nitric oxide content and reductions in glutathione level and SOD and catalase activities. This led to elevations in Caspases 9 and 3 and a reduction in Bcl2 resulting in DNA damage and confirmed by the histopathology of brain tissue. The administration of NAC or safranal with L-T4 prevented these deleterious effects by reducing the oxidative load and improving the brain antioxidant status.

Conclusions: Hyperthyroidism disrupted the neurotransmitters in the brain which aggravated the oxidative stress and resulted in apoptosis. N-Acetylcysteine and safranal prevented these deleterious effects by enhancing the poor antioxidant milieu of the brain.

KEYWORDS:

• Apoptosis
• neurotransmitters
• oxidative stress
• cerebral damage
• monoamine oxidase
• brain histopathology
• dopamine
• serotonin
• norepinephrine

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Notes on contributors

Asmaa S. Shahat

Asmaa S. Shahat, Ph.D., Researcher of Physiology, NODCAR. She has earned her Ph.D from Faculty of Science, Ain Shams University, Cairo.

Wafaa A. Hassan

Wafaa A. Hassan, Professor of Physiology, NODCAR. She has earned a postdoctoral fellowship for six months in Duke University, USA. She has published 14 articles in international peer-reviewed journals. She serves as a peer reviewer for some international journals. She has supervised 4 Ph.D. and 6 M.Sc. students.

Wael M. El-Sayed

Wael M. El-Sayed, Professor of Toxicology, University of Ain Shams. Dr. El-Sayed has earned his Ph.D degree from College of Pharmacy, Utah University, USA followed by Postdoctoral Fellowship for 30 months, sponsored by the Department of Pharmacology and Toxicology, School of Pharmacy, University of Utah, USA. He was awarded the State Incentive Award in Biological Sciences (Molecular Toxicology) in 2008. He has been awarded 14 research grants. He is a member in 8 scientific societies. He has published 49 articles in international peer-reviewed journals (h index 12). He serves as a peer reviewer/associate editor for 15 international journals. He supervised 13 Ph.D. and 15 M.Sc. students. Dr. El-Sayed gave 31 presentations and lectures in international, regional and local conferences.