ABSTRACT
Objective: To investigate the effect of Cannabis sativa extract on the development of neuro- and hepato-toxicity caused by malathion injection in rats. Methods: The extract of Cannabis sativa was obtained from the plant resin by chloroform treatment. Δ-Tetrahydrocannabinol content of the extract (20%) was quantified using gas chromatography-mass spectrometry. The doses of cannabis extract were expressed as Δ -tetrahydrocannabinol content of 10 or 20 mg/kg. Malathion (150 mg/kg) was intraperitoneally administered followed after 30 min by the cannabis extract (10 or 20 mg/kg, subcutaneously). Rats were euthanized 4 h later. Malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide and paraoxonase-1 (PON-1) activity were determined in brain and liver. Brain 5-lipoxygenase and butyrylcholinesterase (BChE) activity were measured as well. Histopathological examination of brain and liver tissue was also performed. Results: Compared to controls, malathion resulted in increased oxidative stress in brain and liver. MDA and nitric oxide concentrations were significantly increased (P<0.05) and GSH significantly decreased with respect to control levels (P<0.05). Malathion also significantly inhibited PON-1 and BChE activities but had no effect on brain 5-lipoxygenase. Brain MDA concentrations were not altered by cannabis treatment. Cannabis at 20 mg/kg, however, caused significant increase in nitric oxide and restored the GSH and PON-1 activity. Brain BChE activity significantly decreased by 26.1% (P<0.05) after treatment with 10 mg/kg cannabis. Cannabis showed no effect on brain 5-lipoxygenase. On the other hand, rats treated with cannabis exhibited significantly higher levels of liver MDA, nitric oxide and PON-1 activity compared with the malathion control group. Rats treated with only malathion exhibited spongiform changes, neuronal damage in the cerebral cortex and degeneration of some Purkinje cells in the cerebellum. There were also hepatic vacuolar degeneration and dilated and congested portal vein. These histopthological changes induced by malathion in brain and liver were reduced to great extent by cannabis administration at 20 mg/kg. Conclusions: Our data suggest that acute treatment with cannabis alleviates the malathion-induced brain and hepatic injury in rats possibly by maintaining the levels of GSH and PON-1 activity.
ABSTRACT
Carbontetrachloride [CCl4] is closely related chemically to chloroform and likewise in hepatic poisons. This study was designed to evaluate the effects of carbon tetrachloride on liver of male rats and the reversing effects of L-carnitine and melatonin on established liver fibrosis. A total of 72 adult male albino rats were used in this study. The animals were divided into six groups. Group [1] animals of the first group were kept as control andtreated with paraffin oil twice weekly for eight weeks. Group [2] rats of the second group were injected with CCl4 intraperitoneally at 0.15 ml per rats [diluted 1:1 in liquid paraffin] twice weekly for eight weeks to produced liver fibrosis. Group [3] following establishment with CCl4 which induced liver fibrosis, the rats were treated with L-carnitine at a dose level of 50 mg/kg for four weeks. Group [4] rats with liver fibrosis were injected intraperitoneally with melatonin at dose level of 10 mg/kg for four weeks. The fifth and sixth groups were given L-carnitine and/or melatonin at dose levels of 50 mg/kg and 10 mg/kg respectively for four weeks. Histological changes in the liver of rats treated with CCl4 including liver fibrosis, architecture distortion and appearance of many pseudolobule. The fibrous tissues run in septa between the nodules. The liver damage varied from one area to another and varied from moderate fibrosis to cirrhosis. Quantitative measurement of the severity of liver fibrosis [area damage] was achieved by using computerized image analysis [Leica image] showed that highly significant increase in area of fibrosis was recorded in the case of rats treated with CCl4 only. Quantitative DNA image analysis showed that 3% of aneuploid cells could be noticed in liver of rats treated with CCl4 only. Histochemical results of rats treated with CCl4 showed highly significant increase in grey level of mucopolysaccharides and protein levels. No histological and histochemical changes could be noticed in the liver of rats treated with either L- carnitine or melatonin only. Both Lcarnitine and melatonin were found to reverse CCl4 induced liver damage