Novel neuroprotective and hepatoprorective effects of citric acid in acute malathion intoxication

Objective: To study the effect of citric acid given alone or combined with atropine on brain oxidative stress, neuronal injury, liver damage, and DNA damage of peripheral blood lymphocytes induced in the rat by acute malathion exposure. Methods: Rats were received intraperitoneal(i.p.) injection of malathion 150 mg/kg along with citric acid(200 or 400 mg/kg, orally), atropine(1 mg/kg, i.p.) or citric acid 200 mg/kg+atropine 1 mg/kg and euthanized 4 h later. Results: Malathion resulted in increased lipid peroxidation(malondialdehyde) and nitric oxide concentrations accompanied with a decrease in brain reduced glutathione, glutathione peroxidase(GPx) activity, total antioxidant capacity(TAC) and glucose concentrations. Paraoxonase-1, acetylcholinesterase(ACh E) and butyrylcholinesterase activities decreased in brain as well. Liver aspartate aminotransferase and alanine aminotransferase activities were raised. The Comet assay showed increased DNA damage of peripheral blood lymphocytes. Histological damage and increased expression of inducible nitric oxide synthase(i NOS) were observed in brain and liver. Citric acid resulted in decreased brain lipid peroxidation and nitric oxide. Meanwhile, glutathione, GPx activity, TAC capacity and brain glucose level increased. Brain ACh E increased but PON1 and butyrylcholinesterase activities decreased by citric acid. Liver enzymes, the percentage of damaged blood lymphocytes, histopathological alterations and i NOS expression in brain and liver was decreased by citric acid. Meanwhile, rats treated with atropine showed decreased brain MDA, nitrite but increased GPx activity, TAC, ACh E and glucose. The drug also decreased DNA damage of peripheral blood lymphocytes, histopathological alterations and i NOS expression in brain and liver. Conclusions: The study demonstrates a beneficial effect for citric acid upon brain oxidative stress, neuronal injury, liver and DNA damage due to acute malathion exposure.

Acetylcholinesterase,butyrylcholinesterase and paraoxonase 1 activities in rats treated with cannabis,tramadol or both

Objective:To investigate the effect of Cannabis sativa resin and/or tramadol,two commonly drugs of abuse on acetylcholinesterase and butyrylcholinesterase activities as a possible cholinergic biomarkers of neurotoxicity induced by these agents.Methods:rats were treated with cannabis resin(5,10 or 20 mg/kg)(equivalent to the active constituent A'-tetrahydrocannabinol),tramadol(5,10 and 20 mg/kg) or tramadol(10 mg/kg)combined with cannabis resin(5,10 and 20 mg/kg) subcutaneously daily for 6 weeks.Acetylcholinesterase(AChE) and butyrylcholinesterase(BChE) activities were measured in brain and serum.We also measured the activity of paraoxonase-1(PONl) in serum of rats treated with these agents.Results:(i) AChE activity in brain increased after 10-20 mg/kg cannabis resin(by 16.3%-36.5%).AChE activity in brain did not change after treatment with 5-20 mg/kg tramadol.The administration of both cannabis resin(5,10 or 20 mg/kg) and tramadol(10 mg/kg) resulted in decreased brain AChE activity by 14.1%,12.9%and 13.6%,respectively;(ii) BChE activity in serum was markedly and dose-dependenlly inhibited by cannabis resin(by 60.9%-76.9%).BChE activity also decreased by 17.6%-36.5%by 10-20mg/kg tramadol and by 57.2%-63.9%by the cannabis resin/tramadol combined treatment;(iii)Cannabis resin at dose of 20 mg/kg increased serum PONl activity by 25.7%.In contrast,tramadol given at 5,10 and 20 mg/kg resulted in a dose-dependent decrease in serum PON1 activity by 19%,36.7%,and 46.1%,respectively.Meanwhile,treatment with cannabis resin plus tramadol resulted in 40.2%,35.8%,30.7%inhibition of PONl activity compared to the saline group.Conclusions:these data suggest that cannabis resin exerts different effects on AChE and BChE activities which could contribute to the memory problems and the decline in cognitive function in chronic users.