Alleviation of Dimethylnitrosamine-Induced Liver Injury and Fibrosis by Supplementation of Anabasis articulata Extract in Rats.

Anabasis articulata (Forssk) Moq. (Chenopodiaceae) is an herb, grows in Egypt, and used in folk medicine to treat diabetes, fever, and kidney infections. The protective and therapeutic effects of the ethanol extract of A. articulata aerial parts were evaluated against dimethylnitrosamine (DMN)-induced liver fibrosis, compared with the standard drug, silymarin. Hepatic hydroxyproline content, serum transforming growth factor-ß1 (TGF-ß1), interleukin 10 (IL-10) and fructosamine were measured as liver fibrosis markers. Hepatic malondialdehyde (MDA), nitric oxide (NO), catalase (CAT), glutathione reductase (GR) and glutathione content (GSH) were measured as oxidant/antioxidant markers. Parallel histopathological investigations were also performed. Protective and therapeutic administration of A. articulata (100 mg/kg daily for 4 weeks), markedly prevented DMN-induced loss in body and liver weights. The extract significantly inhibited the elevation of hepatic hydroxyproline, NO and MDA (P < 0.05), as well as serum fructosamine, and TGF-ß1 (P < 0.05) induced by DMN while it restored IL-10 to normal level in both protective and therapeutic groups. Furthermore, A. articulata prevented the depletion in CAT, GR, and GSH levels (P ≤ 0.05). In addition, oral administration of A. articulata extract and silymarin to both protective and therapeutic groups reduced the increase in liver function enzyme activities; alanine and aspartate amintransferases, gamma-glutamyl transferase in addition to alkaline phosphatase, and caused significant increase in serum albumin concentration as compared to DMN group. These data corresponded closely with those obtained for the drug silymarin. Histopathological studies confirmed the biochemical data and revealed remarkable improvement in liver architecture. Thus, it could be concluded that, A. articulata extract exhibited in vivo hepatoprotective and therapeutic effects against DMN-induced liver injury and may act as a useful agent in controlling the progression of hepatic fibrosis through reduction of oxidative stress and improving liver function.

In vivo Study of a Newly Synthesized Chromen-4-one Derivative as an Antitumor Agent against HCC.

BACKGROUND: Chromenes are a wide group of natural compounds that can be synthesized chemically. The chromen-4-one nucleus acts as a skeleton for varieties of additional active groups that makes the chromene activity vary between antioxidant and anti-inflammatory agents. In the present study, a newly synthesized chromene compound exhibits different behaviors other than anti-inflammatory and antioxidant activities that it is the first time that a member of chromen-4-one compound can control the cancer progress. Inflammation is the first step in tumor development where the severity grade can potentiate tumor growth and progression. In many tumors, pro-inflammatory genes record high expression level such as tumor necrosis factor (TNF-α) and vascular endothelial growth factors (VEGF). These pro-inflammatory factors act as rate limiting steps in tumor initiation, and controlling its expression acts as an early therapeutic way to control the tumor proliferation. The chromone derivatives have biological activities such as anti-inflammatory and anti-tumor activity. METHODS: In the present study, hepatocellular cancer (HCC) induced by diethylnitrosamine (DEN) in rats and then treated with the new chromene derivative and the parameters TNF-α, VEGF, p53, Cyt C, MMP-9, Bcl2, and Bax were measured. RESULTS: The treatment strategy Ch compound is to downregulate pro-inflammatory gene expression of early genes as TNF-α as well as VEGF and subsequently control other factors such as p53, Cyt C, and MMP-9. Also, retrieve the balance between Bcl2 and Bax proteins in DEN-induced HCC in rats. CONCLUSION: The ability of the new Ch derivative to control the primary initiators of HCC such as TNF-α offers this derivative an anti-tumor activity and encourages further researches to follow and monitor its effect on the molecular level.

The activity of detoxifying enzymes in the infective juveniles of Heterorhabditis bacteriophora strains: Purification and characterization of two acetylcholinesterases.

The infectivity and detoxifying enzyme activities including glutathione-S-transferase (GST), acetylcholinesterase (AChE) and carboxylesterase (CaE) are investigated in the infective juveniles (IJs) of six different strains of Heterorhabditis bacteriophora as a biocontrol agent against insect pests. The specific activities ranged from 10.8-29.8 and 50-220units/mg protein for GST and AChE, respectively; and from 24.7-129 and 22.6-77.3units/mg protein for CaE as estimated by P-nitrophenyl and α-naphthyl acetates, respectively. H. bacteriophora EM2 strain has the highest infectivity and the highest enzymatic activities as well. AChE is the predominant detoxifying enzyme that might imply its major role in the detoxification of insecticide(s). The isoenzyme pattern demonstrated two major slow-moving isoforms in all EPN strains examined. Purification of two AChE isoforms, AChEAII and AChEBI, from H. bacteriophora EM2 strain is performed by ammonium sulfate precipitation, gel filtration on Sephacryl S-200 and chromatography on DEAE-Sepharose. AChEAII and AChEBII have specific activities of 1207 and 1560unit/mg protein, native molecular weights of 180 and 68kDa, and are found in dimeric and monomeric forms, respectively. Both isoforms showed optimum activity at pH8.5 and 35°C. AChEBI exhibited higher thermal stability and higher activation energy than AChEAII. The enzymatic activities of purified AChEs are completely inhibited by Hg(+2) and Ni(+2) and greatly enhanced by Mn(+2). The substrate specificity, the relative efficiency of substrates hydrolysis, substrate inhibition and inhibition by BW284C51, but not by iso-OMPA, clearly indicated that they are true AChEs; their properties are compared with those recorded for insects as target hosts for H. bacteriophora EM2.

Egyptian horned viper Cerastes cerastes venom hyaluronidase: purification, partial characterization and evidence for its action as a spreading factor.

Novel Hyaluronidase CcHaseII (33 kDa) of the most dangerous horned viper Cerastes cerastes (Cc) was purified and partial characterized in a set of biochemical assays. CcHaseII was purified by applying a protocol of two successive chromatographic steps; gel filtration on a Sephacryl S-200 and cation exchange chromatography on CM-Sepharose columns. It has specific activity 4000 units/mg protein against 154 units/mg protein for the whole venom with 26-purification fold. The enzymatic activity of the purified Hyaluronidase stimulated by Na(+) and inhibited by entire tested cations, metalloproteinase inhibitors and heparin. CcHaseII (5-10 µg) enhanced one hundred percent of hemorrhagic activity of the potent purified hemorrhagic SVMP of corresponding venom (CcHTI) and enhanced edema-inducing activity of Cc venom in a dose-dependent manner. Furthermore, the described purification procedure allows simple preparation of appreciable quantities of the CcHaseII for further studies. Eventually, exploration of snake venom antigenic parts is the most crucial factor for establishing good immunogens and specific diagnostic reagents.

Serodiagnosis of human intestinal schistosomiasis.

We developed an enzyme linked-immunosorbent assay (ELISA) for serodiagnosis of Schistosoma mansoni infection using a purified immunogenic fraction from schistosome adult worm, obtained by SDS-polyacrylamid gel electrophoresis. Sera from patients with active schistosomiasis (egg passers; n=10); inactive schistosomiasis previously treated with praziquantel (not passing eggs; n=10); fascioliasis, hydatosis (n=5); and healthy controls (n=10) were examined. Western blot analysis revealed that the Sm 31/32 KDa fraction of Schistosoma mansoni is recognized by sera from of both active and inactive schistosomiasis. ELISA IgG reactivity (optical density, OD) to Sm 31/32 KDa fraction by ELISA was significantly higher in sera of schistosomiasis patients (active and inactive), (p<0.001) compared to normal controls, while no significant difference was detected between active (OD=0.79 +/- 0.23) & inactive (OD=0.87 +/- 0.37) patients. No reactivity was detected using facioliasis or hydatosis sera. The overall level of specificity and sensitivity attained was 90% and 93%, respectively. It is concluded that the developed Sm 31/32 KDa ELISA may be of value in serodiagnosis of active and inactive intestinal Schistosoma mansoni infection in humans.

Redox cycling of adrenaline and adrenochrome catalysed by mitochondrial Complex I.

Complex I in bovine heart submitochondrial particles catalyses the NADH-supported generation of superoxide anion; adrenaline is oxidised by superoxide to adrenochrome that, on its hand, is reduced by Complex I, thus establishing a redox cycle that amplifies the superoxide production. The routes in Complex I for superoxide formation and for adrenochrome reduction appear to be different, since they have a different sensitivity to Complex I inhibitors. The results are discussed in terms of current assays for superoxide detection and of pathologies linked to catecholamine oxidation.