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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.
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Objective:To investigate the effect of the prostaglandin E1 analogue misoprostol on oxidative stress and neurodegeration caused by subcutaneous rotenone administration in rats.Methods:Rotenone was administered in a dose of 1.5 mg/kg every other day for 2 weeks. Starting from the 1st day of rotenone injection, rats were subcutaneously treated with misoprostol at doses of 10, 100 or 1 000 μ g/kg. Rats were evaluated for brain lipid peroxidation (malondialdehyde: MDA), reduced glutathione (GSH), nitric oxide (NO) levels, and paraoxonase-1 (PON-1) activity. The concentrations of the anti-apoptotic protein B cell/lymphoma-2 (Bcl-2) were determined in the striatum. Histopathologic examination and the expression of inducible nitric oxide synthase (iNOS) in the cerebral cortex and striatum were also performed.Results:Compared with the vehicle-treated group, rotenone caused a significant increase in brain lipid proxidation (MDA) by 61% (P<0.05) accompanied by an increase in NO by 73.1% (P<0.05) and a decrease in GSH concentration by 29.4% (P<0.05). In addition, brain PON-1 activity significantly decreased by 63.0% (P<0.05) and striatal Bcl-2 significantly decreased by 27.9% (P<0.05) with respect to the corresponding control value. Brain sections from rotenone treated rats showed extensive dark pyknotic and apoptotic nuclei in neurons, shrunken cytoplasm and perineuronal vacuolation. Rotenone also caused pronounced expression of iNOS in the cerebral cortex and striatum. Treatment with misoprostol at doses of 100 and 1 000 μ g/kg resulted in decreased brain MDA (by 16.5%-23.0%) (P<0.05) and NO levels (by 37.1%-40.7%) (P<0.05) and increased GSH concentrations (by 18.8%-30.1%) (P<0.05). PON-1 activity was significantly increased by 80.0%-114.8% (P<0.05) by misoprostol at 100 and 1 000 μ g/kg, respectively. In addition, misoprostol treatment restored striatal Bcl-2 concentrations to its normal value. Misoprostol treatment resulted in markedly reduced brain injury and decreased iNOS expression in the cerebral cortex and striatum of rotenone intoxicated rats.Conclusions:These data suggest that misoprostol prevents the rotenone-induced neurodegeneration in rat brain by reducing brain oxidative stress.
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Objective: To investigate the effect of the prostaglandin E1 analogue misoprostol on oxidative stress and neurodegeration caused by subcutaneous rotenone administration in rats. Methods: Rotenone was administered in a dose of 1.5 mg/kg every other day for 2 weeks. Starting from the 1st day of rotenone injection, rats were subcutaneously treated with misoprostol at doses of 10, 100 or 1 000
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OBJECTIVE@#To investigate the effect of two extracts of Bougainvillea spectabilis (B. spectabilis) flowers with yellow and pink/purple on brain oxidative stress and neuronal damage caused in rats by systemic rotenone injection.@*METHODS@#Rotenone 1.5 mg/kg was given three times per week alone or in combination with B. spectabilis flowers extracts (25 mg or 50 mg) via the subcutaneous route for 2 weeks. Brain concentrations of the lipid peroxidation marker malondialdehyde (MDA), reduced glutathione, nitric oxide (nitrite), the pro-inflammatory cytokine interleukin-1beta (Il-1β) as well as butyrylcholinesterase, and paraoxonase-1 (PON-1) activities, were determined. Histopathology and caspase-3 immunohistochemistry were also performed.@*RESULTS@#Rotenone resulted in significant increases of brain MDA (the product of lipid peroxidation), and nitric oxide content along with decreased brain reduced glutathione. There were also marked and significant inhibition of brain PON-1 and BChE activities and increased Il-1β in brain of rotenone-treated rats. B. spectabilis flowers extract itself resulted in brain oxidative stress increasing both lipid peroxidation and nitrite content whilst inhibiting PON-1 activity. The yellow flowers extract inhibited BChE activity and increased brain Il-1β. When given to rotenone-treated rats, B. spectabilis extracts, however, decreased lipid peroxidation while their low administered doses increased brain GSH. Brain nitrite decreased by the pink extract but showed further increase by the yellow extract. Either extract, however, caused further inhibition of PON-1 activity while the yellow extract resulted in further inhibition of BChE activity. Histopathological studies indicated that both extracts protected against brain, liver and kidney damage caused by the toxicant.@*CONCLUSIONS@#These data indicate that B. spectabilis flowers extracts exert protective effect against the toxic effects of rotenone on brain, liver and kidney. B. spectabilis flowers extracts decreased brain lipid peroxidation and prevented neuronal death due to rotenone and might thus prove the value in treatment of Parkinson's disease.
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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 two extracts of Bougainvillea spectabilis (B. spectabilis) flowers with yellow and pink/purple on brain oxidative stress and neuronal damage caused in rats by systemic rotenone injection. Methods Rotenone 1.5 mg/kg was given three times per week alone or in combination with B. spectabilis flowers extracts (25 mg or 50 mg) via the subcutaneous route for 2 weeks. Brain concentrations of the lipid peroxidation marker malondialdehyde (MDA), reduced glutathione, nitric oxide (nitrite), the pro-inflammatory cytokine interleukin-1beta (Il-1β) as well as butyrylcholinesterase, and paraoxonase-1 (PON-1) activities, were determined. Histopathology and caspase-3 immunohistochemistry were also performed. Results Rotenone resulted in significant increases of brain MDA (the product of lipid peroxidation), and nitric oxide content along with decreased brain reduced glutathione. There were also marked and significant inhibition of brain PON-1 and BChE activities and increased Il-1β in brain of rotenone-treated rats. B. spectabilis flowers extract itself resulted in brain oxidative stress increasing both lipid peroxidation and nitrite content whilst inhibiting PON-1 activity. The yellow flowers extract inhibited BChE activity and increased brain Il-1β. When given to rotenone-treated rats, B. spectabilis extracts, however, decreased lipid peroxidation while their low administered doses increased brain GSH. Brain nitrite decreased by the pink extract but showed further increase by the yellow extract. Either extract, however, caused further inhibition of PON-1 activity while the yellow extract resulted in further inhibition of BChE activity. Histopathological studies indicated that both extracts protected against brain, liver and kidney damage caused by the toxicant. Conclusions These data indicate that B. spectabilis flowers extracts exert protective effect against the toxic effects of rotenone on brain, liver and kidney. B. spectabilis flowers extracts decreased brain lipid peroxidation and prevented neuronal death due to rotenone and might thus prove the value in treatment of Parkinson's disease.
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Objective To investigate the effect of N
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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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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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Obesity is becoming an epidemic health problem. Elevated cytokines and chemokines are prominent features in obesity, which play a main role in the development of other chronic diseases. The aim of this study was to determine the serum levels of monocyte chemoattractant protein-1 [MCP-1], interlukin-6 [IL-6], and serum paraoxonase-1 [PON1] in childhood obesity. The present study included 40 obese school-aged children [5-15 years] and 40 healthy children as controls. The patients were presented to the outpatient clinic in National Institute of Nutrition. MCP-1, IL-6, PON1, total cholesterol, and triglycerides were measured in all participants. The mean serum levels of MCP-1, IL-6, and total cholesterol were significantly higher in obese participants than in controls [P < 0.0001], whereas the PON1 was significantly lower in obese participants than in controls [P < 0.0001]. MCP-1, IL-6, and serum cholesterol levels showed significant positive correlation with BMI [P < 0.05], whereas PON1 showed a significant negative correlation with BMI [P < 0.05]. Multiple regression analysis showed a strong association between PON1 activity and BMI [P < 0.0001]. Childhood obesity is associated with increased serum MCP-1 and IL-6 and decreased PON1 and hypercholesterolemia suggesting an increase in adulthood disease risk. Measuring serum MCP-1, IL-6, PON1 activity in obese children may be a good predictor for future chronic disease development and complications
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Patients with interstitial lung disease [ILD] appear to be at an increased risk of vitamin D deficiency for reasons that are not clear. This study was designed to determine the serum vitamin D level and to evaluate the relationship between the serum level of vitamin D and the underlying etiology, the clinical severity, and pulmonary functions among children with ILD. This cross-sectional case-control study was conducted on 40 patients aged 4-16 years with ILD from those regularly attending the Pediatric Chest Clinic and Pediatric Allergy and Immunology Clinic, Children's Hospital, Ain Shams University. They were divided into two subgroups: 20 patients with nonconnective tissue disease-associated ILD constituted group I and 20 patients with connective tissue disease-associated ILD constituted group II. Twenty apparently healthy children of matched age and sex were recruited as the control group. The mean serum vitamin D [25-hydroxyvitamin D] level was significantly lower among patients with ILDs compared with controls [21.15 +/- 4.6 vs. 48 +/- 40.76 ng/ml, respectively, P < 0.05], and there was no significant difference between patients' subgroups. The mean alkaline phosphatase level was significantly higher in patients with ILDs compared with controls [P < 0.05]. Our patients had a highly significant increase in the total leukocytic count, erythrocyte sedimentation rate, and C-reactive protein in connective tissue disease-associated ILD as compared with nonconnective tissue disease-associated ILD. Serum vitamin D levels showed a significant positive correlation with forced vital capacity and significant negative correlations with the age and the duration of steroid therapy. By linear regression analysis, patients' age and the duration of steroid therapy were significant predictors of low serum vitamin D levels [at P = 0.045 and 0.01, respectively]. Children with ILD appear to be at an increased risk of vitamin D deficiency and insufficiency, particularly those with reduced lung function. All patients with ILD receiving long-term corticosteroid therapy should be considered at increased risk for bone fracture. Preventive measures and routine estimation of vitamin D [25-hydroxyvitamin D] should be recommended and vitamin D supplementation is advised on an individual basis
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This study was designed to assess the relationship between the serum level of 25-hydroxyvitamin D and the clinical, functional severity and the level of asthma control among Egyptian asthmatic children. This case-control cross-sectional study was conducted on 50 asthmatic patients from those regularly attending the Pediatric Chest Clinic, Children's Hospital, Ain Shams University. Twenty healthy children of matched age and sex were recruited as the control group. Pulmonary function tests were significantly decreased in the asthmatic cases compared with the control [P < 0.01]. The serum vitamin D level was found to be significantly decreased in asthmatic children compared with the control group [P < 0.001]. Out of the 50 asthmatic children, 20 had a serum vitamin D level of less than 25 ng/ml, and were considered to be 'vitamin D deficient', whereas the remaining 30 children had a level ranging between >25 ng/ml and
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The present study was conducted to investigate the modulatory effects of silymarin and garlic oil on carbon tetrachloride [CCI4]-induced hepatotoxicity in male albino rats. Animals were orally intoxicated with CCI[4], after 72 hours liver toxicity was assessed. Oral administration with silym4rin or garlic was then continued for 60 days. Serum alanine transaminase [ALT], aspartate transaminase [AST], gamma-glutamyl transaminase[GGT], superoxide dismutase SOD], catalase [CAT], advanced oxidation protein product [AOPP], urinary F2 isoprostanes and 8 hydroxy 2-deoxyguanosine [8-OHdG] were measured. Intoxication of rats with CCI4 induced significant elevation in serum liver enzymes. It also increased oxidative stress through the increase in F2 isoprostanes, AOPP and 8-OHdG, but it reduced SOD and CAT as compared to that of the controls. Oral administration of silymarin or garlic oil improved these adverse effects. Silymarin or garlic has the ability to suppress the occurrence of CCl[4] induced hepatotoxicity in rats by alleviating oxidant status