Pyridine induction of cytochrome P450 1A1, iNOS and metallothionein in Syrian hamsters and protective effects of silymarin

An in vivo assessment for the protective effects of silymarin for pyridine toxicity was investigated through cytochrome P450 isoform CYP1A1 and inducible nitric oxide synthase (iNOS) activity prevention. Moreover, the effect of pyridine-induced oxidative stress on metallothionein I-II (MT), a scavenger of oxygen-derived free radicals, was investigated. Forty Syrian hamsters were allocated into 4 groups. Syrian hamsters were dosed with pyridine (400 mg/kg) intraperitoneally with and without silymarin (200 mg/kg daily by gavage) for 4 days. Pyridine induced diffuse degeneration and necrosis of the proximal and distal renal tubular cells; cloudy swelling, necrosis and hepatocellular atypia of the liver; and degenerative changes in the myocardium. The degree of pathological alterations was less severe with simultaneous silymarin application. CYP1A1, iNOS and MT expression levels were elevated in liver, kidney and heart in response to acute pyridine toxicity. Silymarin application abolished or significantly suppressed the induction of CYP1A1, iNOS and MT expressions in liver, kidney and heart of the pyridine-treated Syrian hamsters. Enhanced synthesis of MT by pyridine possibly implies a purposive cellular response to prevent damage caused by oxygen radicals. However, silymarin significantly reduced the oxidative-stress-inducing effect of pyridine as reflected by decreased synthesis of MT. These results suggest that through oxidant generation, pyridine may cause alteration of the metabolic ways, including nitric oxide-mediated CYP1A1 activity. (c) 2009 Elsevier GmbH. All rights reserved

Hepatoprotective toxicity in mice

L-carnitine is a cofactor in the transfer of long-chain fatty acid allowing the beta-oxidation of fatty acid in the mitochondria. It is also a known antioxidant with protective effects against lipid peroxidation. In this study, hepatoprotective effect of L-carnitine was investigated against acetaminophen (AA)-induced liver toxicity where mitochondrial dysfunction and oxidative stress are thought to be involved in AA hepatotoxicity. Sixty-four Balb/C mice were divided into eight groups. Mice were dosed with single-AA injection (500mg/kg via the intra peritoneal route) with or without L-carnitine (500 mg/kg for 5 days starting 5 days before AA injection via intra peritoneal route) and sampled at 4, 8 and 24 It following AA injection. AA increased serum AST, ALT, total sialic acid (TSA) and MDA as well as tissue TSA and MDA levels significantly with the highest increase observed at 4 h, but there was a decrease in blood and tissue GSH level. Administration Of L-carnitine significantly reduced AA-induced elevations in AST, ALT, TSA and MDA concentrations and increased GSH levels at all sampling points. AA also induced necrosis, hyperemia, sinusoidal congestion and hemorrhage with time-dependent increase in severity, but the degree of necrosis and histopathologic alterations were most severe at 24 h following AA administration. However, the degree of pathologic alterations was less severe with simultaneous L-carnitine application

Evaluation of Cardiac Troponin I and Inducible Nitric Oxide Synthase Expressions in Lambs with White Muscle Disease

White muscle disease (WMD) is a world-wide nutritional disease of all animal species characterised by degeneration of skeletal and cardiac muscles. In the present study we determined the cardiac troponin I (cTnI) and inducible nitric oxide synthase (iNOS) expression in hearts of the lambs with WMD (n = 15). Eight clinically healthy lambs served as control. Creatine kinase (CK), creatine kinase MB (CK-MB), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) activities were analysed for both groups. cTnI levels were measured by a commercially available ELISA kit. Mean cTnI (10.49 +/- 0.25 ng/ml), CK (261.16 +/- 38.61 U/l), CK-MB (214.16 +/- 12.71 U/l), AST (125.83 +/- 1.05), and LDH (228.77 +/- 14.86 U/l) concentrations were higher in WMD cases. Immunohistochemistry revealed definitive loss of cTnI expression in all cases. None of the 8 controls showed loss of the cTnI expression. However, iNOS immunoreactivity was augmented in degenerated cardiac myocytes and macrophages infiltrating to the interstitium compared to controls. The results of the study suggested that cTnI antibody might successfully be used as a sensitive test in the diagnosis of myocardial injury. iNOS expression augments in cardiac myocytes in lambs with WMD, most likely through influencing the signalling pathways to iNOS induction