OBJECTIVE: The current study aimed to investigate the modulatory effects of pyrrolidinedithiocarbamate (PDTC; 100 mg/kg) on bleomycin-induced pulmonary fibrosis (5 mg/kg; intratracheal) in rats.

MATERIALS AND METHODS: Rats were randomly assigned to three groups: normal control, bleomycin control, and PDTC-treated groups. Lung injury was evaluated through histological examination, immunohistochemical detection of inducible nitric oxide synthase (iNOS) in lung tissue and evaluating the total and differential leucocytes count in bronchoalveolar lavage fluid. Lung tissue was used for biochemical assessment of lung content of hydroxyproline, transforming growth factor beta-1 (TGF-β1), tumor necrosis factor-alpha (TNF-α) as well as analysis of lipid peroxides, reduced glutathione (GSH), and total nitrite contents.

RESULTS: PDTC attenuated bleomycin-induced pulmonary fibrosis as evidenced by histological observations, decreased iNOS expression and prevention of bleomycin-induced altered total and differential leukocytes count. Additionally, PDTC caused a significant decrease in lung contents of hydroxyproline, TGF-β1, TNF-α, lipid peroxides, and total nitrite coupled with increase in lung GSH content as compared to bleomycin control group.

CONCLUSION: PDTC attenuated bleomycin-induced pulmonary fibrosis in rats via its anti-inflammatory, antioxidant, and antifibrotic activities.

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.