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OBJECTIVE@#To investigate the effect of N-nitro-l-arginine methyl ester (l-NAME), a non-selective nitric oxide synthase (NOS) inhibitor, and 7-nitroindazole (7-NI), a selective neuronal NOS inhibitor, on oxidative stress and tissue damage in brain and liver and on DNA damage of peripheral blood lymphocytes in malathion intoxicated rats.@*METHODS@#Malathion (150 mg/kg) was given intraperitoneally (i.p.) along with l-NAME or 7-NI (10 or 20 mg/kg, i.p.) and rats were euthanized 4 h later. The lipid peroxidation product malondialdehyde (MDA), nitric oxide (nitrite), reduced glutathione (GSH) concentrations and paraoxonase-1 (PON-1) activity were measured in both brain and liver. Moreover, the activities of glutathione peroxidase (GPx) acetylcholinesterase (AChE), and butyrylcholinesterase (BChE), total antioxidant capacity (TAC), glucose concentrations were determined in brain. Liver enzyme determination, Comet assay, histopathological examination of brain and liver sections and inducible nitric oxide synthase (iNOS) immunohistochemistry were also performed.@*RESULTS@#(i) Rats treated with only malathion exhibited increased nitric oxide and lipid peroxidation (malondialdehyde) accompanied with a decrease in GSH content, and PON-1 activity in brain and liver. Glutathione peroxidase activity, TAC, glucose concentrations, AChE and BChE activities were decreased in brain. There were also raised liver aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and increased DNA damage of peripheral blood lymphocytes (Comet assay). Malathion caused marked histopathological changes and increased the expression of iNOS in brain and liver tissues. (ii) In brain of malathion-intoxicated rats, l-NAME or 7-NI resulted in decreased nitrite and MDA contents while increasing TAC and PON1 activity. Reduced GSH and GPx activity showed an increase by l-NAME. AChE activity increased by 20 mg/kg l-NAME and 10 mg/kg 7-NI. AChE activity decreased by the higher dose of 7-NI while either dose of 7-NI resulted in decreased BChE activity. (iii) In liver of malathion-intoxicated rats, decreased MDA content was observed after l-NAME or 7-NI. Nitrite level was unchanged by l-NAME but increased after 7-NI which also resulted in decreased GSH concentration and PON1 activity. Either inhibitor resulted in decreased liver ALT activity. (iv) DNA damage of peripheral blood lymphocytes was markedly inhibited by l-NAME or 7-NI treatment. (v) iNOS expression in brain and liver decreased by l-NAME or 7-NI. (vi) More marked improvement of the histopathological alterations induced by malathion in brain and liver was observed after 7-NI compared with l-NAME.@*CONCLUSIONS@#In malathion intoxicated rats, the neuronal NOS inhibitor 7-NI and to much less extent l-NAME were able to protect the brain and liver tissue integrity along with improvement in oxidative stress parameters. The decrease in DNA damage of peripheral blood lymphocytes by NOS inhibitors also suggests the involvement of nitric oxide in this process.
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Objective To investigate the effect of N
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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 Δ
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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 (AChE) 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 (iNOS) 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 AChE increased but PON1 and butyrylcholinesterase activities decreased by citric acid. Liver enzymes, the percentage of damaged blood lymphocytes, histopathological alterations and iNOS 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, AChE and glucose. The drug also decreased DNA damage of peripheral blood lymphocytes, histopathological alterations and iNOS 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.
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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 (AChE) 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 (iNOS) 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 AChE increased but PON1 and butyrylcholinesterase activities decreased by citric acid. Liver enzymes, the percentage of damaged blood lymphocytes, histopathological alterations and iNOS 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, AChE and glucose. The drug also decreased DNA damage of peripheral blood lymphocytes, histopathological alterations and iNOS 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.
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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 Δ-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 (PON1) 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-dependently inhibited by cannabis resin (by 60.9-76.9%). BChE activity also decreased by 17.6-36.5% by 10-20 mg/kg tramadol and by 57.2-63.9% by the cannabis resin/tramadol combined treatment; (iii) Cannabis resin at doses of 20 mg/kg increased serum PON1 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 PON1 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.
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Background: High salt intake induces renal-stress. The present study was carried out to examine the therapeutic effects of proximol[Halfa bar extract], lasilactonedrug[Spironolactone+Furosemide] and their combination on renal-stressed rats
Material and Methods: Thirty five male rats were used and divided into five groups. The first group served as negative control and received fresh tap water orally for four weeks. The animals in the other four groups drank hypertonic saline solution [2% NaCl] as a sole source of drinking water for four weeks to induce the animal model of renal stress. Then the renal-stressed rats were further divided into: positive control, renal-stressed rats treated daily with proximol [7.8 mg/kg b.wt], renal-stressed rats treated daily with lasilactone [3.9 mg/kg b.wt], and renal- stressed rats treated daily with a combination of proximol and lasilactone for four weeks. The levels of aldosterone, sodium, potassium, calcium, urea, uric acid and creatinine were measured in the sera of rats. Nitric oxide [NO], reduced glutathione [GSH] and lipid peroxidation [MDA] levels were also measured in the homogenate of renal tissue
Results: In the renal-stressed group, there was a significant increase in levels of aldosterone, sodium, calcium, urea, uric acid, NO and MDA and a significant decrease in potassium and GSH as compared to control group. Although the treatment of renal stressed rats with proximol, lasilactone and their combination reduced the increased level of aldosterone induced in renal stressed rats, aldosterone level was still higher than the control value. In addition, the treatment with proximol, lasilactone and their combination restored the significant increase in sodium, NO and lipid peroxidation to non significant changes as compared to control group. Also the decreased levels of GSH induced in renal-stressed rats returned to non significant changes. However, potassium decreased significantly below the control and the model groups with the combined treatment. Furthermore, treatment with proximol, lasilactone and their combination reduced the elevated levels of uric acid and urea induced by hypertonic saline solution to control- like values in the case of uric acid and to a significant decrease in the case of urea
Conclusion: In conclusion, proximol, lasilactone and their combination have an effective role in ameliorating the changes in the levels of aldosterone, serum electrolytes, oxidative stress and consequently the disturbance in kidney functions in renal-stressed rats induced by hypertonic saline solution