Protective effect of low molecular weight fucoidan on aspirin induced stomach ulceration in rats

Diabetic cardiomyopathy (DCM) is characterized by cardiac dysfunction and cardiomyocyte apoptosis. Oxidative stress is suggested to be the major contributor to the development of DCM. This study was intended to evaluate the protective effect of low molecular weight fucoidan (LMWF) against cardiac dysfunction in diabetic rats. Type 2 diabetic goto-kakizaki rats were untreated or treated with LMWF (50 and 100 mg/kg/day) for three months. The establishment of DCM model and the effects of LMWF on cardiac function were evaluated by echocardiography and isolated heart perfusion. Ventricle staining with H-E or Sirius Red was performed to investigate the structural changes in myocardium. Functional evaluation demonstrated that LMWF has a beneficial effect on DCM by enhancing myocardial contractility and mitigating cardiac fibrosis. Additionally, LMWF exerted significant inhibitory effects on the reactive oxygen species production and myocyte apoptosis in diabetic hearts. The depressed activity of superoxide dismutase in diabetic heart was also improved by intervention with LMWF. Moreover, LMWF robustly inhibited the enhanced expression of protein kinase Cβ, an important contributor to oxidative stress, in diabetic heart and high glucose-treated cardiomyocytes. In conclusion, LMWF possesses a protective effect against DCM through ameliorations of PKCβ-mediated oxidative stress and subsequent cardiomyocyte apoptosis in diabetes.

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Favourable influence of low molecular weight heparin in mitigating the peroxidative membrane damage induced by a cytotoxic agent and an atherogenic diet

Human & Experimental Toxicology ◽

10.1191/0960327103ht348oa ◽

2003 ◽

Vol 22 (5) ◽

pp. 229-235 ◽

Cited By ~ 10

Author(s):

P R Deepa ◽

P Varalakshmi

Keyword(s):

Lipid Peroxidation ◽

Molecular Weight ◽

Antioxidant Enzymes ◽

Protective Effect ◽

Erythrocyte Membrane ◽

Low Molecular Weight Heparin ◽

Atherogenic Diet ◽

Control Group ◽

Low Molecular Weight ◽

Cholesterol Levels

The present study is aimed to demonstrate the protective effect of a heparin derivative, low molecular weight heparin (LMWH) against erythrocyte membrane injury. Two models serve to induce membrane lipid peroxidative damage, namely a potent cytotoxic agent, adriamycin and a hypercholesterolemic atherogenic diet. Two groups of male Wistar rats (1409-10 g) received a single intravenous injection of adriamycin (ADR, 7.5 mg/kg), while two other groups were fed an atherogenic diet comprising a supplementation of 4% cholesterol, 1% cholic acid and 0.5% thiouracil (CCT diet) for 2 weeks. For each of the above two groups, LMWH (Troparin; 300 mg/day per rat subcutaneously) treatment commenced on day 8 and continued for a week. One group was maintained as the normal control group, and another group that received only LMWH treatment was designated as the LMWH drug control group. Erythrocyte membrane was isolated and assayed for its cholesterol levels, lipid peroxidation and ATPases activity. The activities of antioxidant enzymes were assessed in the haemolysate. The findings of the study were that both adriamycin and the atherogenic diet produced elevated membrane cholesterol levels and lipid peroxidation. The membrane ATPases suffered loss in activity. Accentuated oxidative stress was marked by rise in the activities of antioxidant enzymes (SOD, catalase and GPx). LMWH intervention reverted these changes thereby normalizing the membrane composition and function. The membrane protective effect of LMWH is illuminated by this work.

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A New Synthetic Protease Inhibitor, E-3123, Prevents Lysosomal and Mitochondrial Fragility in Rat Caerulein-Induced Pancreatitis

Journal of International Medical Research ◽

10.1177/030006059202000302 ◽

1992 ◽

Vol 20 (3) ◽

pp. 211-217

Author(s):

T Hirano ◽

T Manabe

Keyword(s):

Molecular Weight ◽

Acute Pancreatitis ◽

Protease Inhibitor ◽

Protective Effect ◽

Malate Dehydrogenase ◽

Cathepsin B ◽

Exocrine Pancreas ◽

Low Molecular Weight

The study investigated the protective effect of a new synthetic protease inhibitor, E-3123, a 4-guanidinobenzoate methanesulphonate, on the exocrine pancreas in caerulein-induced pancreatitis of rats both in vivo and in vitro. Hyperamylasaemia, pancreatic oedema and congestion of amylase, as well as cathepsin B leakage from lysosomes and malate dehydrogenase leakage from mitochondria, were prevented by infusion of 5 mg/kg.h E-3123 particularly when infused for 2 h before and during 5 μg/kg.h caerulein infusion for 3.5 h. The results indicate that E-3123 plays its protective roles against pancreatitis in the subcellular compartments such as lysosomes and mitochondria, and that such a low molecular weight protease inhibitor as E-3123 may be clinically useful in the treatment of acute pancreatitis.

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