Influence of C-phycocyanin on hepatocellular parameters related to liver oxidative stress and Kupffer cell functioning.
OBJECTIVE
Kupffer cells, liver macrophages involved in immunomodulation, phagocytosis, and biochemical attack, can induce cytotoxicity and inflammation when their activity is exacerbated. The aim of this study was to evaluate the effects of C-phycocyanin on Kupffer cell functioning considering its antioxidant and anti-inflammatory properties.


METHODS
Actions of C-phycocyanin on colloidal carbon phagocytosis, carbon-induced respiratory burst activity, and sinusoidal lactate dehydrogenase (LDH) release were studied in isolated perfused mouse liver. The influence of C-phycocyanin on tumor necrosis factor-a (TNF-alpha) and nitrite levels in serum and liver nitric oxide synthase (NOS) activity was assessed in rats subjected to thyroid hormone (T3) administration, a condition known to underlie hepatic oxidative stress comprising an increased Kupffer cell activity.


RESULTS
C-phycocyanin elicited a concentration-dependent inhibition of carbon phagocytosis and carbon-induced O2 uptake (IC50 = 0.2 mg/ml) by perfused livers, with a 52% diminution in the carbon-induced sinusoidal release of LDH being found at a concentration of 0.25 mg/ml. Thyroid calorigenesis induced an 82-fold increase in serum TNF-alpha levels, an effect that was suppressed by pretreatment with C-phycocyanin, the antioxidant alpha-tocopherol, and by the Kupffer cell inactivator gadolinium chloride. C-phycocyanin also suppressed the T3-induced increases in serum nitrite levels (234%) and in the activity of hepatic NOS (75%).


CONCLUSIONS
C-phycocyanin significantly decreases Kupffer cell phagocytosis and the associated respiratory burst activity, effects that may contribute to the abolition of oxidative stress-induced TNF-alpha response and NO production by hyperthyroid state.
Remirez
D
D
Centro de Investigaciones del Ozono, Centro Nacional de Investigaciones Científicas, Ciudad de la Habana, Cuba. ozono@infomed.sld.cu
Fernández
V
V
Tapia
G
G
González
R
R
Videla
L A
LA
D000818:Animals; D002244:Carbon / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D010798:Phycocyanin / Q000494:pharmacology*; D051381:Rats; D016897:Respiratory Burst / Q000187:drug effects; D014284:Triiodothyronine / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D014284:Triiodothyronine; D010798:Phycocyanin; D002244:Carbon; D007770:L-Lactate Dehydrogenase; D019001:Nitric Oxide Synthase