Diadelis Remirez

Inhibitory effects of Spirulina in zymosan-induced arthritis in mice

The anti-inflammatory effect of microalgae Spirulina was studied in zymosan-induced arthritis in mice. Four days after the intra-articular injection of zymosan (15 mg/ml), Spirulina (100 and 400 mg/kg perorally) was administered to animals for 8 days. The mice were than killed and beta-glucuronidase was measured in the synovial fluid. Each knee joint was totally removed for histopathological studies. Spirulina significantly reduced the levels of beta-glucuronidase that had been increased by zymosan. Histopathological and ultrastructural studies showed inhibition of the inflammatory reaction, whereas no destruction of cartilage, well-preserved chondrocytes, and normal rough endoplasmic reticulum and mitochondria were seen. The anti-arthritic effect exerted by Spirulina as shown in this model may be at least partly due to the previously reported antiinflammatory and antioxidative properties of its constituent, phycocyanin. To our knowledge, this is the first report on the anti-inflammatory effect of Spirulina in an experimental model of arthritis.

Role of histamine in the inhibitory effects of phycocyanin in experimental models of allergic inflammatory response

It has recently been reported that phycocyanin, a biliprotein found in the blue-green microalgae Spirulina, exerts anti-inflammatory effects in some animal models of inflammation. Taking into account these findings, we decided to elucidate whether phycocyanin might exert also inhibitory effects in the induced allergic inflammatory response and on histamine release from isolated rat mast cells. In in vivo experiments, phycocyanin (100, 200 and 300mg/kg post-orally (p.o.)) was administered 1 h before the challenge with 1 microg of ovalbumin (OA) in the ear of mice previously sensitized with OA. One hour later, myeloperoxidase activity and ear edema were assessed. Phycocyanin significantly reduced both parameters. In separate experiments, phycocyanin (100 and 200 mg/kg p.o.) also reduced the blue spot area induced by intradermal injections of histamine, and the histamine releaser compound 48/80 in rat skin. In concordance with the former results, phycocyanin also significantly reduced histamine release induced by compound 48/80 from isolated peritoneal rat mast cells. The inhibitory effects of phycocyanin were dose dependent. Taken together, our results suggest that inhibition of allergic inflammatory response by phycocyanin is mediated, at least in part, by inhibition of histamine release from mast cells.

Effect of phycocyanin in zymosan-induced arthritis in mice—phycocyanin as an antiarthritic compound

The antiinflammatory effect of a phycocyanin extract was studied in zymosan‐induced arthritis model in mice. Four days after the intraarticular injection of zymosan, (15 mg/ml), phycocyanin (25, 50, and 100 mg/kg p.o) was administered to animals for 8 days. The mice were then killed and the synovial fluid measured for β‐glucuronidase. Each knee joint was totally removed for histopathological and ultrastructural studies. Phycocyanin significantly reduced the levels of β‐glucuronidase that had been increased by zymosan. Histopathological and ultrastructural studies showed inhibition in cellular infiltration and reduction of synovial hyperplasia and synovitis. The antiinflammatory activity exerted by phycocyanin may be due, at least in part, to its antioxidative properties, although inhibitory effects on both arachidonic acid metabolism and cytokine production such as tumor necrosis factor (TNF) may also be involved. To our knowledge, this is the first report on the antiinflammatory effect of phycocyanin in an experimental model of arthritis. Drug Dev. Res. 48:70–75, 1999.

Mechanism of protection of lobenzarit against paracetamol-induced toxicity in rat hepatocytes

Abstract The protective effects of lobenzarit, an antioxidative agent and antirheumatic drug, on the cytotoxicity of paracetamol in rat hepatocytes were studied, as well as the inhibitory effects of lobenzarit on cytochrome P-450s and glutathione S -transferases (GSTs) in rat liver. Paracetamol was selected as a model toxin, since it is known to be bioactivated by specific cytochrome P-450s presumably to N -acetyl- p -benzoquinoneimine, a reactive metabolite which upon overdasage of paracetamol causes protein and non-protein thiol depletion, lipid peroxidation and cytotoxicity measurable as LDH leakage. At concentrations of lobenzarit of 0.2 and 0.3 mM, added 30 min before paracetamol, the drug prevented paracetamol-induced leakage of lactate dehydrogenase (LDH) almost completely and lipid peroxidation (LPO) and depletion of glutathione (GSH) substantially and also the formation of the 3-glutathionyl conjugate of paracetamol. However, at a concentration of 0.05 mM lobenzarit did not protect anymore against the paracetamol toxicity. When added to the hepatocytes 1 h and 2 h before paracetamol, 0.05 and 0.2 and 0.3 mM concentrations of lobenzarit did not protect against the cytotoxicity induced by paracetamol either. Lobenzarit did not inhibit cytochromes P-450 1A1/1A2, 2B1/2B2 abd 2E1 which were measured as ethoxyresorufin O -deethylation (EROD) activity in β-naphthoflavone-induced rat liver microsomes, as pentoxyresorufin de-pentylation (PROD) activity in phenobarbital-induced microsomes and as p -nitrophenol hydroxylation (PNPH) activity in pyrazol-induced microsomes. Lobenzarit did not show inhibition of glutathione S -transferase (GST) activity towards 1-chloro-2,4-dinitrobenzene (CDNB) in cytosol from liver of rats treated with phenobarbital, pyrazol and β-naphthoflavone either. It is concluded that the cytoprotective effect of lobenzarit is most likely due to its antioxidant effects and/or to its ability to stimulate GSH reductase.

Protective effects of lobenzarit against allyl alcohol-induced hepatotoxicity in mice and rats

The protective effects of lobenzarit disodium against the toxicity of allyl alcohol were investigated in vitro using isolated rat hepatocytes and in vivo using mice. In mice, at i.p doses of 25, 50 and 100 mg/kg lobenzarit significantly decreased the activity of alanine amino transferase (ALT) in serum and the concentration of malondialdehyde (MDA) in liver homogenates, both of which were increased by allyl alcohol at a dose of 64 mg/kg. At concentrations of 0.2 and 0.3 mM, lobenzarit reduced the release of lactate dehydrogenase (LDH) and the levels of malondialdehyde (MDA) induced by 0.4 mM of allyl alcohol in isolated rat hepatocytes. However, lobenzarit did not increase the levels of reduced glutathione (GSH) depleted by allyl alcohol in any of the two experimental models. The protective effects of lobenzarit were dose- and concentration-dependent and they were most obvious when lobenzarit was administered 30 min before allyl alcohol. It is concluded that lobenzarit exerts the observed protective effects most likely by its antioxidant properties.