Potential antioxidant properties and hepatoprotective effects of Juniperus phoenicea berries against CCl4 induced hepatic damage in rats.

OBJECTIVE: To investigate the antioxidant and hepatoprotective properties of Juniperus phoenicea (J. phoenicea) berries against CCl4-induced oxidative damage in rats. METHODS: Hepatotoxicity was induced in albino Wistar rats by single dose of CCl4 dissolved in olive oil (1 mL/kg BW, 1/1 in olive oil, i.p.). Aqueous extract of J. phoenicea berries (AEJP) was administered at the dose of 250 mg/kg/day by gavage for 12 days. RESULTS: Obtained results revealed that administration of CCl4 caused a significant increase in plasma ASAT, ALAT, ALP and LDH activities and total bilirubin concentration, compared to the control group. While, albumin and total protein concentration were significantly lower. Additionally, a significant decrease in the level of hepatic GSH, GPx and GST activities associated with a significant increase of MDA content in CCl4 group than those of the control. However, the treatment of experimental rats with AEJP prevented these alterations and maintained the antioxidant status. The histopathological observations supported the biochemical evidences of hepatoprotection. CONCLUSIONS: The results of the present investigation indicate that J. Phoenicea possesses hepatoprotective activity and this effect was may be due to its antioxidant properties.

Hepatoprotective activity of Peganum harmala against ethanol-induced liver damages in rats.

In this study, we investigated the protective effects of Peganum harmala seeds extract (CPH) against chronic ethanol treatment. Hepatotoxicity was induced in male Wistar rats by administrating ethanol 35% (4 g/kg/day) for 6 weeks. CPH was co-administered with ethanol, by intraperitonial (IP) injection, at a dose of 10 mg/kg bw/day. Control rats were injected by saline solution (NaCl 9‰). Chronic ethanol administration intensified lipid peroxidation monitored by an increase of TBARS level in liver. Ethanol treatment caused also a drastic alteration in antioxidant defence system; hepatic superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities. A co-administration of CPH during ethanol treatment inhibited lipid peroxidation and improved antioxidants activities. However, treatment with P. harmala extract protects efficiently the hepatic function of alcoholic rats by the considerable decrease of aminotransferase contents in serum of ethanol-treated rats.

Protective effects of Hammada scoparia flavonoid-enriched fraction on liver injury induced by warm ischemia/reperfusion.

CONTEXT: Hepatic ischemia/reperfusion injury (IRI) is a major cause of liver damage during liver surgery and transplantation. Plants have historically been used in treating liver damage, and Hammada scoparia (Pomel) (Chenopodiaceae) has been reported to possess a broad spectrum of pharmacological and therapeutic activities. OBJECTIVE: In this study, a flavonoid-enriched fraction was used before the warm ischemia (WI) process as pharmacological preconditioning and in combination with technical postconditioning to evaluate their protective effects. MATERIALS AND METHODS: The rats were divided into five groups: a sham group; a control group (Control-IR) that was submitted to 60 min WI; a Pharmacological Preconditioning group (PreC-IR) that received flavonoid-enriched fraction (200 mg/kg body weight); a Postconditioning group (PostC) and a PreC + PostC group. RESULTS: The use of the flavonoid-enriched fraction was noted to significantly (p < 0.05) reduce liver injury, as evidenced by the decrease in liver transaminase activities (AST and ALT) and lactic dehydrogenase (LDH), alkaline phosphatase (ALP), and lipid peroxidation (TBARS), levels as well as the enhancement of antioxidant enzymes (catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx)) responses. The results also indicated that, compared with the separate application of pharmacological preconditioning and postconditioning, the combination of both treatments was more effective in reducing tissue oxidative stress levels through modulating SOD, GSH-PX, and CAT activities. Furthermore, the combined protocol further decreased the liver morphological score compared with solo treatment. DISCUSSION AND CONCLUSION: Overall, the results indicate that the H. scoparia flavonoid-enriched fraction could be a promising candidate for future application as a pharmacological preconditioning agent against hepatic IRI.

Chronic neuroprotective effects of low concentration lithium on SH-SY5Y cells: possible involvement of stress proteins and gene expression.

To investigate the molecular mechanism underlying the neuroprotective effect of lithium on cells, in this study, we exposed SH-SY5Y cells to 0.5 mmol/L lithium carbonate (Li2CO2) for 25-50 weeks and then detected the expression levels of some neurobiology related genes and post-translational modifications of stress proteins in SH-SY5Y cells. cDNA arrays showed that pyruvate kinase 2 (PKM2) and calmodulin 3 (CaM 3) expression levels were significantly down-regulated, phosphatase protein PP2A expression was lightly down-regulated, and casein kinase II (CK2), threonine/tyrosine phosphatase 7 (PYST2), and dopamine beta-hydroxylase (DBH) expression levels were significantly up-regulated. Besides, western blot analysis of stress proteins (HSP27, HSP70, GRP78 and GRP94) showed an over-expression of two proteins: a 105 kDa protein which is a hyper-phosphorylated isoform of GRP94, and a 108 kDa protein which is a phosphorylated tetramer of HSP27. These results suggest that the neuroprotective effects of lithium are likely related to gene expressions and post-translational modifications of proteins cited above.

Protective effects of aqueous extract of Hammada scoparia against hepatotoxicity induced by ethanol in the rat.

Aqueous extract (AE) of Hammada scoparia leaves was chemically characterized and its hepatoprotective activities were investigated in vivo in rat model. Wistar rats were treated daily with 35% ethanol solution (3 g/kg/day) during 4 weeks and fed with basal diet or basal diet containing AE (200 mg/kg/day). Control rats were treated with saline solution and fed with basal diet. The bioactivity of AE against ethanol-induced oxidative stress in rat liver was studied in order to explore its hepatoprotective effects. H. scoparia extract used at 200 mg/kg body weight significantly prevented the effects of ethanol, which induced a hepatic pathological damage and increased the levels of the serum markers of the enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP). Concomitantly, with these changes, this extract also prevented ethanol-induced oxidative stress in the rat liver as evidenced by the decreased lipid peroxidation level, a considerable decrease in the activities of AST, ALT and ALP and restoring the activities of antioxidant enzymes: superoxide dismutase, catalase and glutathione peroxidase. These biochemical changes were consistent with histopathological observations suggesting marked hepatoprotective effect of the AE of H. scoparia.

Antioxidant activity and hepatoprotective potential of Hammada scoparia against ethanol-induced liver injury in rats

The present work was aimed at studying the antioxidative activity and hepatoprotective effects of methanolic extract (ME) of Hammada scoparia leaves against ethanol-induced liver injury in male rats. The animals were treated daily with 35 % ethanol solution (4 g kg−1 day−1) during 4 weeks. This treatment led to an increase in the lipid peroxidation, a decrease in antioxidative enzymes (catalase, superoxide dismutase, and glutathione peroxidase) in liver, and a considerable increase in the serum levels of aspartate and alanine aminotransferase and alkaline (..)(AU)

Antioxidant activity and hepatoprotective potential of Hammada scoparia against ethanol-induced liver injury in rats.

The present work was aimed at studying the antioxidative activity and hepatoprotective effects of methanolic extract (ME) of Hammada scoparia leaves against ethanol-induced liver injury in male rats. The animals were treated daily with 35 % ethanol solution (4 g kg(-1) day(-1)) during 4 weeks. This treatment led to an increase in the lipid peroxidation, a decrease in antioxidative enzymes (catalase, superoxide dismutase, and glutathione peroxidase) in liver, and a considerable increase in the serum levels of aspartate and alanine aminotransferase and alkaline phospahatase. However, treatment with ME protects efficiently the hepatic function of alcoholic rats by the considerable decrease in aminotransferase contents in serum of ethanol-treated rats. The glycogen synthase kinase-3 ß was inhibited after ME administration, which leads to an enhancement of glutathione peroxidase activity in the liver and a decrease in lipid peroxidation rate by 76 %. These biochemical changes were consistent with histopathological observations, suggesting marked hepatoprotective effect of ME. These results strongly suggest that treatment with methanolic extract normalizes various biochemical parameters and protects the liver against ethanol induced oxidative damage in rats.

Hammada scoparia flavonoids and rutin kill adherent and chemoresistant leukemic cells.

In search for compounds able to reduce cell adhesion-mediated drug resistance (CAM-DR), we studied effects of Hammada scoparia extracts on leukemic cells adherent or in suspension. We show that H. scoparia flavonoidic fraction and its compound rutin induce apoptosis specifically in adherent leukemic cells and abolish CAM-DR. Importantly, rutin inhibited survival of adherent leukemic progenitors (CD34(+)38(-)123(+)) but spared normal progenitors (CD34(+)38(-)). The pro-apoptotic effects of rutin were correlated with a decrease of active GSK3ß and inhibitors of GSK3ß reproduced rutin-induced cytotoxicity. This study uncovers the potential of H. scoparia flavonoids and rutin to overcome CAM-DR in acute myeloid leukemia.

A New alpha5beta1 integrin-dependent survival pathway through GSK3beta activation in leukemic cells.

BACKGROUND: Cell survival mediated by integrin engagement has been implicated in cell adhesion-mediated drug resistance. We have recently demonstrated that the activation of glycogen synthase kinase 3 beta (GSK3beta) is a new pathway supporting the chemoresistance of leukemic cells adhered to fibronectin. METHODOLOGY AND PRINCIPAL FINDINGS: We show here that in conditions of serum starvation, the fibronectin receptor alpha(5)beta(1) integrin, but not alpha(4)beta(1), induced activation of GSK3beta through Ser-9 dephosphorylation in adherent U937 cells. The GSK3beta-dependent survival pathway occurred in adherent leukemic cells from patients but not in the HL-60 and KG1 cell lines. In adhesion, activated GSK3beta was found in the cytosol/plasma membrane compartment and was co-immunoprecipitated with alpha(5) integrin, the phosphatase PP2A and the scaffolding protein RACK1. PP2A and its regulatory subunit B' regulated the Ser-9 phosphorylation of GSK3beta. In adherent leukemic cells, alpha(5)beta(1) integrin but not alpha(4)beta(1) upregulated the resistance to TNFalpha-induced apoptosis. Both extrinsic and intrinsic apoptotic pathways were under the control of alpha(5)beta(1) and GSK3beta. CONCLUSIONS AND SIGNIFICANCE: Our data show that, upon serum starvation, alpha(5)beta(1) integrin engagement could regulate specific pro-survival functions through the activation of GSK3beta.