Effects of Solanum lycopersicum L. (tomato) against isoniazid and rifampicin induced hepatotoxicity in wistar albino rats

Abstract Anti-tuberculosis drugs are reported to cause hepatotoxicity, which varies from asymptomatic rise of the hepatic enzymes. Hepatoprotective plants plays important role to protect liver. This study investigated the hepatoprotective potential of the Solanum lycopersicum in rats intoxicated with Isoniazid and Rifampicin (INH+RIF) to induce hepatotoxicity. Thirty wistar albino rats were divided into five groups of six animals each. Group 1 rats were kept control while groups II, III, IV and V were administered with INH+RIF (75+150 mg/kg) orally, for seven consecutive days. For treatment, rats in group III received silymarin while animals in group IV and V were provided with 40 mg/kg and 80 mg/kg of Solanum lycopersicum extract, respectively. On day 0 and 8th blood samples were collected for the analysis of hepatic biomarkers. The data were subjected to one-way ANOVA and Bonferronis post hoc test for statistical analysis. Hepatotoxicity induced by INH+RIF resulted in significant elevation of serum hepatic enzymes including Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), and total bilirubin while decreased the albumin level. The Solanum lycopersicum at dose of 80 mg/kg significantly reduced the hepatic enzymes AST, ALT, ALP and bilirubin while the albumin level was significantly increased. The treatment had non-significant effect on body and liver weight. Drug induced hepatotoxicity can be effectively treated with Solanum lycopersicum at 80 mg/kg dose.

Resumo As drogas antituberculose são relatadas como causadoras de hepatotoxicidade, ocasionando o aumento assintomático das enzimas hepáticas. As plantas hepatoprotetoras desempenham um papel importante na proteção do fígado. Este estudo investigou o potencial hepatoprotetor de Solanum lycopersicum em ratos que foram intoxicados com isoniazida e rifampicina (INH + RIF) para induzir hepatotoxicidade. Trinta ratos wistar albinos foram divididos em cinco grupos de seis animais cada. Os ratos do grupo 1 representaram o grupo controle, enquanto os ratos dos grupos II, III, IV e V receberam INH + RIF (75 + 150 mg/kg) por via oral, por sete dias consecutivos. Para o tratamento, os ratos do grupo III receberam silimarina, enquanto os animais do grupo IV e V receberam 40 mg/kg e 80 mg/kg de extrato de S. lycopersicum, respectivamente. Nos dias 0 e 8, foram coletadas amostras de sangue para análise de biomarcadores hepáticos. Os dados foram submetidos a teste unilateral (ANOVA) e post hoc de Bonferroni para análise estatística. A hepatotoxicidade induzida por INH + RIF resultou em elevação significativa das enzimas hepáticas séricas, incluindo aspartato aminotransferase (AST), alanina aminotransferase (ALT), fosfatase alcalina (ALP) e bilirrubina total, enquanto houve a diminuição do nível de albumina. O S. lycopersicum, na dose de 80 mg / kg, reduziu significativamente as enzimas hepáticas AST, ALT, ALP e bilirrubina, enquanto o nível de albumina aumentou de forma significativa. O tratamento não teve efeito significativo no peso corporal e hepático. A hepatotoxicidade induzida por drogas pode ser tratada de forma eficaz com S. lycopersicum na dose de 80 mg/kg.

Effects of Solanum lycopersicum L. (tomato) against isoniazid and rifampicin induced hepatotoxicity in wistar albino rats / Efeitos de Solanum lycopersicum L. (tomate) contra hepatotoxicidade induzida por isoniazida e rifampicina em ratos albinos wistar

Anti-tuberculosis drugs are reported to cause hepatotoxicity, which varies from asymptomatic rise of the hepatic enzymes. Hepatoprotective plants plays important role to protect liver. This study investigated the hepatoprotective potential of the Solanum lycopersicum in rats intoxicated with Isoniazid and Rifampicin (INH+RIF) to induce hepatotoxicity. Thirty wistar albino rats were divided into five groups of six animals each. Group 1 rats were kept control while groups II, III, IV and V were administered with INH+RIF (75+150 mg/kg) orally, for seven consecutive days. For treatment, rats in group III received silymarin while animals in group IV and V were provided with 40 mg/kg and 80 mg/kg of Solanum lycopersicum extract, respectively. On day 0 and 8th blood samples were collected for the analysis of hepatic biomarkers. The data were subjected to one-way ANOVA and Bonferroni's post hoc test for statistical analysis. Hepatotoxicity induced by INH+RIF resulted in significant elevation of serum hepatic enzymes including Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), and total bilirubin while decreased the albumin level. The Solanum lycopersicum at dose of 80 mg/kg significantly reduced the hepatic enzymes AST, ALT, ALP and bilirubin while the albumin level was significantly increased. The treatment had non-significant effect on body and liver weight. Drug induced hepatotoxicity can be effectively treated with Solanum lycopersicum at 80 mg/kg dose.

As drogas antituberculose são relatadas como causadoras de hepatotoxicidade, ocasionando o aumento assintomático das enzimas hepáticas. As plantas hepatoprotetoras desempenham um papel importante na proteção do fígado. Este estudo investigou o potencial hepatoprotetor de Solanum lycopersicum em ratos que foram intoxicados com isoniazida e rifampicina (INH + RIF) para induzir hepatotoxicidade. Trinta ratos wistar albinos foram divididos em cinco grupos de seis animais cada. Os ratos do grupo 1 representaram o grupo controle, enquanto os ratos dos grupos II, III, IV e V receberam INH + RIF (75 + 150 mg/kg) por via oral, por sete dias consecutivos. Para o tratamento, os ratos do grupo III receberam silimarina, enquanto os animais do grupo IV e V receberam 40 mg/kg e 80 mg/kg de extrato de S. lycopersicum, respectivamente. Nos dias 0 e 8, foram coletadas amostras de sangue para análise de biomarcadores hepáticos. Os dados foram submetidos a teste unilateral (ANOVA) e post hoc de Bonferroni para análise estatística. A hepatotoxicidade induzida por INH + RIF resultou em elevação significativa das enzimas hepáticas séricas, incluindo aspartato aminotransferase (AST), alanina aminotransferase (ALT), fosfatase alcalina (ALP) e bilirrubina total, enquanto houve a diminuição do nível de albumina. O S. lycopersicum, na dose de 80 mg / kg, reduziu significativamente as enzimas hepáticas AST, ALT, ALP e bilirrubina, enquanto o nível de albumina aumentou de forma significativa. O tratamento não teve efeito significativo no peso corporal e hepático. A hepatotoxicidade induzida por drogas pode ser tratada de forma eficaz com S. lycopersicum na dose de 80 mg/kg.

Effects of Solanum lycopersicum L. (tomato) against isoniazid and rifampicin induced hepatotoxicity in wistar albino rats.

Anti-tuberculosis drugs are reported to cause hepatotoxicity, which varies from asymptomatic rise of the hepatic enzymes. Hepatoprotective plants plays important role to protect liver. This study investigated the hepatoprotective potential of the Solanum lycopersicum in rats intoxicated with Isoniazid and Rifampicin (INH+RIF) to induce hepatotoxicity. Thirty wistar albino rats were divided into five groups of six animals each. Group 1 rats were kept control while groups II, III, IV and V were administered with INH+RIF (75+150 mg/kg) orally, for seven consecutive days. For treatment, rats in group III received silymarin while animals in group IV and V were provided with 40 mg/kg and 80 mg/kg of Solanum lycopersicum extract, respectively. On day 0 and 8th blood samples were collected for the analysis of hepatic biomarkers. The data were subjected to one-way ANOVA and Bonferroni's post hoc test for statistical analysis. Hepatotoxicity induced by INH+RIF resulted in significant elevation of serum hepatic enzymes including Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), and total bilirubin while decreased the albumin level. The Solanum lycopersicum at dose of 80 mg/kg significantly reduced the hepatic enzymes AST, ALT, ALP and bilirubin while the albumin level was significantly increased. The treatment had non-significant effect on body and liver weight. Drug induced hepatotoxicity can be effectively treated with Solanum lycopersicum at 80 mg/kg dose.

Role of the purinergic P2Y2 receptor in hippocampal function in mice.

OBJECTIVE: The aim of this study is to investigate the role of the purinergic P2Y2 receptor in learning and memory processes. MATERIALS AND METHODS: Behavioral, electrophysiological, and biochemical tests of memory function were conducted in P2Y2 receptor knockout (P2Y2R-KO) mice, and the findings were compared to those of wild-type mice with the help of unpaired Student's t-test. RESULTS: The findings of the behavioral Y-maze test showed that the P2Y2R-KO mice had impaired memory and cognitive function. Electrophysiological studies on paired-pulse facilitation showed that glutamate release was higher in the P2Y2R-KO mice than in the WT mice. Furthermore, PCR and Western blot analysis revealed that the mRNA and protein expression of acetylcholinesterase E (AChE) and alpha-7 nicotinic acetylcholine receptors (α7 nAChRs) were increased in the hippocampus of P2Y2R-KO mice. CONCLUSIONS: The findings of this study indicate that P2Y2 receptors are important regulators of both glutamatergic and cholinergic systems in the hippocampus.

Impaired ILK Function Is Associated with Deficits in Hippocampal Based Memory and Synaptic Plasticity in a FASD Rat Model.

Fetal Alcohol Spectrum Disorder (FASD) is an umbrella term that encompasses a wide range of anatomical and behavioral problems in children who are exposed to alcohol during the prenatal period. There is no effective treatment for FASD, because of lack of complete characterization of the cellular and molecular mechanisms underlying this condition. Alcohol has been previously characterized to affect integrins and growth factor signaling receptors. Integrin Linked Kinase (ILK) is an effector of integrin and growth-factor signaling which regulates various signaling processes. In FASD, a downstream effector of ILK, Glycogen Synthase Kinase 3ß (GSK3ß) remains highly active (reduced Ser9 phosphorylation). GSK3ß has been known to modulate glutamate receptor trafficking and channel properties. Therefore, we hypothesize that the cognitive deficits accompanying FASD are associated with impairments in the ILK signaling pathway. Pregnant Sprague Dawley rats consumed a "moderate" amount of alcohol throughout gestation, or a calorie-equivalent sucrose solution. Contextual fear conditioning was used to evaluate memory performance in 32-33-day-old pups. Synaptic plasticity was assessed in the Schaffer Collateral pathway, and hippocampal protein lysates were used to evaluate ILK signaling. Alcohol exposed pups showed impaired contextual fear conditioning, as compared to control pups. This reduced memory performance was consistent with decrease in LTP as compared to controls. Hippocampal ILK activity and GSK3ß Ser21/9 phosphorylation were significantly lower in alcohol-exposed pups than controls. Increased synaptic expression of GluR2 AMPA receptors was observed with immunoprecipitation of post-synaptic density protein 95 (PSD95). Furthermore, immunoprecipitation of ILK revealed a decreased interaction with GluR2. The ILK pathway appears to play a significant role in memory and synaptic plasticity impairments in FASD rats. These impairments appear to be mediated by reduced GSK3ß regulation and increased synaptic stabilization of the calcium-impermeable GluR2 AMPA receptors.