Pyrrolidine dithiocarbamate protects against scopolamine-induced cognitive impairment in rats

Citation:
Abd-El-Fattah, M. A., N. F. Abdelakader, and H. F. Zaki, "Pyrrolidine dithiocarbamate protects against scopolamine-induced cognitive impairment in rats", European Journal of Pharmacology, vol. 723, pp. 330-338, 2014.

Abstract:

Alzheimer's disease (AD) is a chronic neurodegenerative disorder that leads to disturbances of cognitive
functions. Although the primary cause of AD remains unclear, brain acetylcholine deficiency, oxidative
stress and neuroinflammation may be considered the principal pathogenic factors. The present study was
constructed to investigate the anti-amnestic effect of pyrrolidine dithiocarbamate (PDTC) on
scopolamine-induced behavioral, neurochemical and biochemical changes in rats. PDTC (50 and
100 mg/kg) and donepezil (2.5 mg/kg) were orally administered for 14 successive days. Dementia was
induced at the end of the treatment period by a single injection of scopolamine (20 mg/kg; i.p.), and
Y-maze test was conducted 30 min thereafter. Rats were then sacrificed and homogenates of cortical and
hippocampal tissues were used for the estimation of noradrenaline, dopamine, serotonin and heat shock
protein 70 contents along with acetylcholinesterase activity. In addition, certain oxidative stress markers,
pro-inflammatory and anti-inflammatory cytokines were assessed. Histological examination of cortical
and hippocampal tissues was also performed. Scopolamine resulted in memory impairment that was
coupled by alterations in the estimated neurotransmitters, heat shock protein 70, acetylcholinesterase
activity, oxidative stress as well as inflammatory biomarkers. Histological analysis revealed serious
damaging effects of scopolamine on the structure of cerebral cortex and hippocampus. Pretreatment of
rats with PDTC in both doses mitigated scopolamine-induced behavioral, biochemical, neurochemical
and histological changes in a manner comparable to donepezil. The observed anti-amnestic effect of
PDTC makes it a promising candidate for clinical trials in patients with cognitive impairment.

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