Hepatoprotective activity of phloretin and hydroxychalcones against Acetaminophen Induced hepatotoxicity in mice

Polyphenolics form a major part of the dietary antioxidant capacity of fruits and vegetables have been identified as chemopreventive or anticancer agents. Hydroxychalcones are polyphenols abundantly distributed throughout the plant kingdom and are compounds with two aromatic rings (benzene or phenol) and an unsaturated side chain. In the present study, effect of phloretin (apple major flavonoid), 4-hydroxychalcone and 4'-hydroxychalcone were investigated against acetaminophen-induced acute liver damage. The study was designed as multiple dose pre- and post-treatments. Mice were administratedacetaminophen (1g/kg and 640 mg/kg for mortality and acute toxicity experiments, respectively). Mortality rate, serum transaminases (SGOT and SGPT) and histological examination were applied. Acetaminophen produced 100% mortality at the dose of 1 g/kg in mice, while pre-treatment and post-treatment (i.p., twice daily for 48 hrs) of animals with phloretin and 4-hydroxychalcone (50 mg/kg) and 4'-hydroxychalcone (25 mg/kg) significantly reduced the mortality rate. Acetaminophen produced acute toxicity at the dose of 640 mg/kg in mice, while pre- and post-treatments of animals with phloretin and hydroxychalcones significantly lowered the rise in SGOT and SGPT. Liver sections collected for histological examination showed cellular changes including centrilobular necrosis, extensive portal inflammation, and micro and macro vesicular structures in the acetaminophen group. These cellular changes were reduced following treatment of mice with Phloretin and hydroxychalcones. Taken collectively, from the results of this study it may be suggested that phloretin and hydroxychalcones have hepatoprotective activity against acetaminophen liver injury in mice

Biosynthesis and recovery of selenium nanoparticles and the effects on matrix metalloproteinase-2 expression

Today, green synthesis of nanoparticles is attracting increasing attention. In the present study, the Bacillus sp. MSh-1 was isolated from the Caspian Sea (located in the northern part of Iran) and identified by various identification tests and 16S ribosomal DNA analysis. The reduction time course study of selenium ion (Se4+) reduction by using this test strain was performed in a liquid culture broth. Then, the intracellular NPs (nanoparticles) were released by the liquid nitrogen disruption method and thoroughly purified using an n-octyl alcohol water extraction system. Characterization of the separated NPs on features such as particle shape, size and purity was carried out with different devices. The energy dispersive X-ray and X-ray diffraction patterns showed that the purified NPs consisted of only selenium and are amorphous respectively. In addition, the transmission electron micrograph showed that the separated NPs were spherical and 80–220 nm in size. Furthermore, the cytotoxicity effect of these extracted biogenic selenium (Se) NPs on the fibrosarcoma cell line (HT-1080) proliferation and the inhibitory effect of the Se NPs on MMP-2 (matrix metalloproteinase-2) expression were studied using the MTT [3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyl-2H-tetrazolium bromide] assay and gelatin zymography. Biogenic Se NPs showed a moderately inhibitory effect on MMP-2 expression

Acute and subacute toxicity of novel biogenic selenium nanoparticles in mice

Context: In the present investigation, acute and subacute toxicity of the biogenic Se nanoparticles (Se NPs) has been reported. Objective: To characterize the Se NPs produced by a bacterium species and to evaluate their toxicity and impact on clinical chemistry and hematological parameters of NMRI mice. Materials and methods: The Se NPs were prepared by Bacillus sp. MSh-1 in a culture medium containing SeO2 (1.26 mM) and their physiochemical properties investigated using TEM, XRD and FT-IR. The LD50 of Se NPs and SeO2 were determined and the subacute toxicity evaluated by orally administration of 0, 2.5, 5, 10 and 20 mg kg−1 of Se NPs to male mice for 14 consecutive days. Parameters of blood cells, AST, ALT, ALP, creatinine, BUN, cholesterol, bilirubin, triglyceride and CPK were experimentally measured. Results: The XRD and TEM analyses showed that the spherical NPs were amorphous, in the size range of 80–220 nm. The toxicological evaluation showed that the LD50 values of SeO2 and Se NPs were 7.3 and 198.1 mg kg−1, respectively. No biochemical changes were observed from the administration of 2.5, 5 and 10 mg kg−1 of Se NPs, but a dose of 20 mg kg−1 was accompanied with signs of toxicity including lower body weight and changes in clinical chemistry and hematological parameters. Conclusion: The biogenic Se NPs were less toxic than synthetic Se NPs and much less (26-fold) toxic than the SeO2, which demonstrates the important role of Bacillus sp. MSh-1 in conversion of a highly toxic Se compound to the less toxic Se NPs. Keywords: L

Azole Antifungal Drugs and Cytochrome P450 Induction.

The potential inducing ability of azole antifungal drugs on cytochrome P450 isozymes, in particular the P4504A subfamily, have been investigated in vivo and in vitro. In rat liver, bifonazole (1-(P,α-diphenylbenzyl) imidazole), but not the structurally related clotrimazole, was found to induce the cytochrome P4504A subfamily (similar to clofibrate), based on their relative abilities to induce lauric acid ω-hydroxylase activity, immunochemical reactivity with an antibody raised against P4504A1, and Northern blotting with a cytochrome P4504A1 cDNA probe. Additionally, bifonazole was subsequently shown to be a peroxisome proliferator, inducing peroxisomal palmitoyl-CoA oxidation, trifunctional protein, and associated hepatomegaly. Furthermore, immunoblotting data demonstrated that bifonazole also induces P4501A1 and 2B1/2 proteins, and the P4503A subfamily. By contrast, clotrimazole did not induce the cytochrome P4504A subfamily, but did induce P4502B1/2 proteins and the P4503A subfamily, and to a lesser extent P4501A1. In rat kidney, based on the ability to induce lauric acid w-hydroxylase activity, cytochrome P4504A1 apoprotein, and cytochrome P4504A1 mRNA, bifonazole, but not clotrimazole, was found to be a weak inducer of the cytochrome P4504A subfamily. In addition, bifonazole at the high dose level was able to cause only slight increases in kidney cytochromes P4501A1 and P4502B1/2 proteins, and the P4503A subfamily, as judged by EROD, PROD, and immunoblotting assays. Bifonazole was also able to induce the trifunctional protein (similar to clofibrate), but did not induce peroxisomal palmitoyl-CoA activity. In vitro, using rat hepatocyte primary cultures, clofibrate and all of the other azole antimycotic agents studied (except itraconazole), namely bifonazole, clotrimazole, geniconazole, miconazole, and UK-47265, maintained levels of total cytochrome P450 over the 70 hours culture period as compared to the freshly isolated cells. However, only bifonazole and clofibrate were able to induce lauric acid 11- and 12-hydroxylase activities, and cytochrome P4504A1 apoprotein. The apparent EC50 values for bifonazole and clofibrate for the induction of the 11- and 12-hydroxylation of lauric acid, demonstrated that bifonazole is 160 and 44 times more potent than clofibrate, respectively. In order to explain the inductive effect observed by bifonazole, molecular modelling of the interaction of the test compounds with the putative binding site of the recently isolated receptor, PPAR, were investigated. The results showed a more facile docking of bifonazole and clofibric acid with the PPAR than the other imidazole agents, as reflected in more favourable AG values. Taken collectively, results of the present study further substantiate the close relationship between induction of P4504A1 and peroxisome proliferation, in vivo and in vitro. In addition, the result of molecular modelling studies is not inconsistent with the involvement of the PPAR in P4504A1 induction and peroxisome proliferation