Protective effect of crude extract from Wedelia paludosa (Asteraceae) on the hepatotoxicity induced by paracetamol in mice.

Several in-vitro and in-vivo ethnopharmacological studies carried out with plants of the genus Wedelia have already demonstrated hepatoprotective effects in chemically-induced liver injury, including those induced by paracetamol. Here, the effects of the crude extract from Wedelia paludosa on paracetamol-induced hepatotoxicity in mice was investigated. Intraperitoneal injection of paracetamol (1,000 mg kg(-1)) caused 80% death after 24 h in mice, which was significantly reduced by oral pretreatment with W. paludosa (500 mg kg(-1)). Hepatotoxicity was observed 24 h after an intraperitoneal injection of paracetamol (600 mg kg(-1)), as evidenced by an increase in plasma activity of aspartate and alanine aminotransferases. That hepatotoxicity was significantly attenuated by W. paludosa pretreatment (100-500 mg kg(-1)) in a dose-response manner. Paracetamol (1,000 mg kg(-1)) drastically depleted total glutathione levels and decreased glutathione peroxidase and delta-aminolevulinate dehydratase activity in the liver, such effects not being prevented by pretreatment with W. paludosa. Neither paracetamol treatment alone nor pretreatment with W. paludosa altered glutathione reductase and glutathione S-transferase activity or the levels of end-products of lipid peroxidation. In conclusion, we found that W. paludosa protected against paracetamol-induced hepatotoxicity, an effect not observed over oxidative stress-related parameters. Hepatoprotection is likely mediated by some terpenes present in W. paludosa extract. However, further studies will be required to explain the mechanisms involved in the hepatoprotection afforded by W. paludosa.

Long-lasting neuropathic pain induced by brachial plexus injury in mice: Role triggered by the pro-inflammatory cytokine, tumour necrosis factor alpha.

Brachial plexus avulsion (BPA) resulted in a marked and long-lasting mechanical hypernociception (up to 80 days) in comparison to a sham-operated group, as assessed by Von Frey filaments, in both Swiss and C57/BL6 mice. In the tail-flick test, both Swiss and C57/BL6 mice submitted to BPA showed a significant thermal hypernociception, which persisted for 10 days. Both mechanical and thermal hypernociception following BPA were abolished in tumour necrosis factor alpha (TNFalpha) p55 receptor knockout mice. Moreover, the mechanical hypernociception caused by BPA was inhibited by the local application of the anti-TNFalpha (10 and 100 ng/site) antibody at the time of the surgery or by the intravenous administration (100 microg/kg) of this antibody at the time of the surgery or 4 days after the BPA. A similar inhibition of the mechanical hypernociception was observed when treating mice with the TNFalpha synthesis inhibitor thalidomide (50 mg/kg, s.c.), either at the time of the surgery or 4 days after. The results suggest that the persistent thermal, and especially the persistent mechanical, hypernociception observed following BPA in mice is largely dependent on the generation of TNFalpha. Based on these results, it is possible to suggest that therapeutic strategies for blocking TNFalpha could represent a valuable approach for the treatment of persistent neuropathic pain.

Effect of subchronic treatment with mercury chloride on NTPDase, 5'-nucleotidase and acetylcholinesterase from cerebral cortex of rats.

The aim of the present investigation was to evaluate the effect of a subchronic treatment (30 days/30 doses) with subcutaneous injections (0.1 mg/kg) of HgCl2 on NTPDase (E.C. 3.6.1.5), 5'-nucleotidase (E.C 3.1.3.5) and acetylcholinesterase (AChE, E.C. 3.1.1.7) activities in brain from adult rats. NTPDase and 5'-nucleotidase were measured in cortical synaptosomal fraction and AChE was measured in the homogenate of cerebral cortex and hippocampus. After the subchronic treatment (30 days), NTPDase activity was enhanced approximately 35% (p < 0.05) with ATP and ADP as substrates and no difference was observed in 5'-nucleotidase activity (AMP hydrolysis). In addition, AChE activity was enhanced in the cerebral cortex (22%, p < 0.05) and hippocampus (26%, p < 0.05) after the subchronic treatment. Mercury deposited in brain was measured by cold vapor (atomic absorption spectrometry) and no difference between the control and the subchronically treated group was observed. Here we showed for the first time that exposure to low levels of Hg2+, which resembles occupational exposure to low levels of mercury, caused a marked increase in NTPDase and AChE activities. The relationship of these alterations with the neurotoxicity of inorganic mercury deserves further studies.

Extrato da casca de Syzygium cumini no controle da glicemia e estresse oxidativo de ratos normais e diabéticos / Syzygium cumini bark extract in controling glycemia and oxidative stress of normal and diabetic rats

O Syzygium cumini, também conhecido como Jamboläo é amplamente utilizado na medicina popular para o tratamento da diabetes melito. Este estudo verificou a eficiência do extrato da casca de Syzygium cumini sobre os níveis glicêmicos e estresse oxidativo de ratos normais e diabéticos induzidos por aloxano. Os animais foram divididos em grupo controle (C), controle tratado (CT), diabético controle (DC) e diabético tratado (DT). A administraçäo oral do extrato aquoso da casca de Jamboläo, na dose de 1g/kg de peso vivo, por um período de trinta dias, näo resultou em uma reduçäo significativa na glicemia e nos níveis de hemoglobina glicosilada. Neste estudo, o tratamento com o extrato demonstrou um aumento dos níveis de substâncias reativas ao ácido tiobarbitúrico (TBA-RS) no plasma dos ratos do grupo DT (P<0,05), comparado com o C. A atividade da catalase nos rins dos ratos do grupo DC diminuiu significativamente (P<0,01) e no fígado houve uma elevaçäo significativa dessa enzima no grupo DC (P<0,01). Estes resultados indicam que o extrato da casca do Jamboläo näo possui efeito hipoglicemiante em ratos diabéticos induzidos pelo aloxano. O efeito antioxidante desta planta näo foi suficiente para diminuir significativamente a produçäo de TBA-RS. A diminuiçäo da atividade da catalase nos rins pode ser devida à exaustäo ou inibiçäo desta enzima e seu aumento, no fígado, devido ao estresse oxidativo, ocasionado pelo estado diabético

In vitro effects of L-arginine and guanidino compounds on NTPDase1 and 5'-nucleotidase activities from rat brain synaptosomes.

Tissue accumulation of arginine (Arg), N-acetylarginine (NA), argininic acid (AA) and homoarginine (HA) occurs in hyperargininemia, an inborn error of the urea cycle. In the present study, we investigated the in vitro effects of Arg, NA, AA and HA on NTPDase1 and 5'-nucleotidase activities from synaptosomal cerebral cortex of rats. The results showed that Arg enhances NTPDase1 activity at the high concentrations tested (1.5 and 3.0mM) for both the ATP and ADP nucleotides. Activation was also observed with other guanidino compounds tested: NA, AA and HA activated ATP and ADP hydrolysis in all experiments at the concentration of 25 microM. Besides this, NA and AA activated ATP hydrolysis at a lower concentration (1 microM). In another set of experiments, we verified the effect of Arg on purified apyrase at pH 8.0 and 6.5 and observed an increase in the enzyme activity at all Arg concentrations tested (0.01-3.0mM). In contrast, Arg and the other guanidino compounds tested did not alter 5'-nucleotidase activity. These results suggest that changes in nucleotide hydrolysis may be involved in the brain dysfunction caused by hyperargininemia amongst other potential pathophysiological mechanisms involved in this condition.

Extrato da casca de Syzygium cumini no controle da glicemia e estresse oxidativo de ratos normais e diabéticos

The plant Syzygium cumini, also known as Black Plum is used widely in the popular medicine for the treatment of diabetes mellitus. This study verified the efficiency of the extract of the bark of Syzygium cumini on the glycemic levels and oxidative stress of normal and diabetic rats induced by alloxan. The animals were divided in control group (C), control treatment group (CT), diabetic control group (DC) and diabetic treatment group (DT). Oral administration of the aqueous extract of the bark of Syzygium cumini, in the dose of 1g/kg live weight, for a period of thirty days, did not result in a significant reduction on glycemia or on glucosilated hemoglobin levels. The treatment with the extract demonstrated an increase in the levels of thiobarbituric acid reactive substances (TBA-RS) in the plasma of the DT group (P 0.05), compared to the C. Kidney catalase activity of rats in DC group decreased significantly (P 0.01) and, in the liver, it showed a significant elevation in group DC (P 0.01). Those results indicated that the extract of Syzygium cumini bark does not possess hypoglycemic effect in alloxan diabetic induced rats. The antioxidant effect of this plant was not enough to reduce the production of TBA-RS significantly. The decrease of catalase activity in the kidneys can be owed to its exhaustion or inhibition, and its increase in the liver could be due to oxidative stress caused by the diabetic status.

O Syzygium cumini, também conhecido como Jambolão é amplamente utilizado na medicina popular para o tratamento da diabetes melito. Este estudo verificou a eficiência do extrato da casca de Syzygium cumini sobre os níveis glicêmicos e estresse oxidativo de ratos normais e diabéticos induzidos por aloxano. Os animais foram divididos em grupo controle (C), controle tratado (CT), diabético controle (DC) e diabético tratado (DT). A administração oral do extrato aquoso da casca de Jambolão, na dose de 1g/kg de peso vivo, por um período de trinta dias, não resultou em uma redução significativa na glicemia e nos níveis de hemoglobina glicosilada. Neste estudo, o tratamento com o extrato demonstrou um aumento dos níveis de substâncias reativas ao ácido tiobarbitúrico (TBA-RS) no plasma dos ratos do grupo DT (P 0,05), comparado com o C. A atividade da catalase nos rins dos ratos do grupo DC diminuiu significativamente (P 0,01) e no fígado houve uma elevação significativa dessa enzima no grupo DC (P 0,01). Estes resultados indicam que o extrato da casca do Jambolão não possui efeito hipoglicemiante em ratos diabéticos induzidos pelo aloxano. O efeito antioxidante desta planta não foi suficiente para diminuir significativamente a produção de TBA-RS. A diminuição da atividade da catalase nos rins pode ser devida à exaustão ou inibição desta enzima e seu aumento, no fígado, devido ao estresse oxidativo, ocasionado pelo estado diabético.

Extrato da casca de Syzygium cumini no controle da glicemia e estresse oxidativo de ratos normais e diabéticos

The plant Syzygium cumini, also known as Black Plum is used widely in the popular medicine for the treatment of diabetes mellitus. This study verified the efficiency of the extract of the bark of Syzygium cumini on the glycemic levels and oxidative stress of normal and diabetic rats induced by alloxan. The animals were divided in control group (C), control treatment group (CT), diabetic control group (DC) and diabetic treatment group (DT). Oral administration of the aqueous extract of the bark of Syzygium cumini, in the dose of 1g/kg live weight, for a period of thirty days, did not result in a significant reduction on glycemia or on glucosilated hemoglobin levels. The treatment with the extract demonstrated an increase in the levels of thiobarbituric acid reactive substances (TBA-RS) in the plasma of the DT group (P 0.05), compared to the C. Kidney catalase activity of rats in DC group decreased significantly (P 0.01) and, in the liver, it showed a significant elevation in group DC (P 0.01). Those results indicated that the extract of Syzygium cumini bark does not possess hypoglycemic effect in alloxan diabetic induced rats. The antioxidant effect of this plant was not enough to reduce the production of TBA-RS significantly. The decrease of catalase activity in the kidneys can be owed to its exhaustion or inhibition, and its increase in the liver could be due to oxidative stress caused by the diabetic status.

O Syzygium cumini, também conhecido como Jambolão é amplamente utilizado na medicina popular para o tratamento da diabetes melito. Este estudo verificou a eficiência do extrato da casca de Syzygium cumini sobre os níveis glicêmicos e estresse oxidativo de ratos normais e diabéticos induzidos por aloxano. Os animais foram divididos em grupo controle (C), controle tratado (CT), diabético controle (DC) e diabético tratado (DT). A administração oral do extrato aquoso da casca de Jambolão, na dose de 1g/kg de peso vivo, por um período de trinta dias, não resultou em uma redução significativa na glicemia e nos níveis de hemoglobina glicosilada. Neste estudo, o tratamento com o extrato demonstrou um aumento dos níveis de substâncias reativas ao ácido tiobarbitúrico (TBA-RS) no plasma dos ratos do grupo DT (P 0,05), comparado com o C. A atividade da catalase nos rins dos ratos do grupo DC diminuiu significativamente (P 0,01) e no fígado houve uma elevação significativa dessa enzima no grupo DC (P 0,01). Estes resultados indicam que o extrato da casca do Jambolão não possui efeito hipoglicemiante em ratos diabéticos induzidos pelo aloxano. O efeito antioxidante desta planta não foi suficiente para diminuir significativamente a produção de TBA-RS. A diminuição da atividade da catalase nos rins pode ser devida à exaustão ou inibição desta enzima e seu aumento, no fígado, devido ao estresse oxidativo, ocasionado pelo estado diabético.