Biochemical, Immunological, DNA and Histopathological Changes Caused by Cannabis Sativa in the Rat
DOI:
https://doi.org/10.12974/2309-6179.2014.01.01.2Keywords:
Brain, Cannabis sativa, comet assay, liver, metabolic effects.Abstract
The aim of this study was to investigate the effect of repeated administration of Cannabis sativa extract on some biochemical, immunological parameters, on DNA damage and on brain and liver histology in the rat. Rats received either saline or Cannabis sativa at 5, 10 or 20 mg/kg (expressed as ?9-tetrahydrocannabinol), intraperitoneally daily for 30 days. Cholesterol, triglycerides, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), total proteins, glucose were determined in serum. DNA fragmentation was measured in the liver. The level of DNA damage of peripheral blood mononuclear cells (PBMCs) was evaluated by alkaline single cell gel electrophoresis (comet assay). Brain and liver histopathology and caspase-3 immunohistochemistry were performed. Cannabis treatment resulted in increased cholesterol (41.2% by 20 mg/kg cannabis) and triglycerides (17.8-31.8% by 10-20 mg/kg cannabis). HDL-C decreased by 21.9-38.4% while LDL-C increased by 14.7-174.7% by 10-20 mg/kg cannabis. Total proteins were unaltered but glucose increased by 34.2-53.3% by 10-20 mg/kg of cannabis. CD4 increased by 16.6-19.5% by 10-20 mg/kg cannabis. Liver DNA fragmentation increased by 16.7% after cannabis at 20 mg/kg. The comet percentage of PBMCs was higher after 5, 10 and 20 mg/kg cannabis (7.0 ± 0.36, 9.0 ± 0.92 and 21.0 ± 0.97) than that in saline control group (5 ± 0.36). Cannabis caused dark neurons, decreased size of nuclei, cellular infiltration and increased caspase-3 immunoreactivity. In the liver, cannabis treatment was associated with fibrosis, vacuolar degeneration, cellular infiltration in the portal area, dilatation of portal vein and positive reaction to caspase-3 antibody. These effects of cannabis were dose-dependent.
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