To investigate the effects and mechanisms of melatonin on immunological liver injury in mice.

To investigate the profile of endostatin on adjuvant arthritis (AA) and angiogenesis blockade in synovitis. METHODS: The model of rat AA was induced by injection of intradermal complete Freund's adjuvant (CFA). Hind paw volume of rat was measured by volume meter and the activities of interleukin-1 (IL-1) and IL-2 were measured by the assay of thymocytes proliferation. IL-1β and tumor necrosis factor-α (TNF-α) produced by synoviocytes was estimated with radioimmunoassay. The number of new blood vessels in knee joint synovium was counted under microscope by hematoxylin and eosin (HE) staining. RESULTS: The secondary inflammation of AA rats appeared on the 10th day after injection of CFA. The therapeutic administration of endostatin (0.1, 0.5, and 2.5mg·kg-1·d-1, sc, ×7d) was given from that time (d 10). It was found that endostatin significantly inhibited the secondary paw swelling and the number of new blood vessels in the synovium of AA rats. Endostatin significantly decreased the production of IL-1 derived from both peritoneal macrophages and synoviocytes and IL-2 from splenocytes, especially at the dose of 2.5mg/kg. This effect of endostatin also was seen on TNF-α produced by synoviocytes. CONCLUSION: The recombinant human endostatin had an inhibitory effect on rat AA, which was related to its anti-angiogenesis and inhibition of proinflammatory cytokines.

To study the effects and mechanisms of melatonin (MT) on immune responses in mice of different months. METHODS: Thymocyte proliferation and IL-2 activity were assayed by 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) and activated mouse splenocyte proliferation methods, respectively; cAMP and methionine-enkephalin (met-Enk) level was determined by competitive protein binding assay and radioimmunoassay, respectively. RESULTS: The function of lymphocytes, obtained from BALB/c mice aged 6 and 11 months were decreased, which was restored by melatonin at the dose of 5 mg/kg or 30 mg/kg. In vitro, proliferation of lymphocytes in 11-month-old mice was decreased and cAMP level was increased. Melatonin (0.1nmol/L or 1mmol/L) had negative regulation to this. Forskolin (10 mmol/L) enhanced the cAMP level of lymphocytes in 2-and 11-month-old mice (P<0.01), which was antagonized partially by melatonin and this effect of melatonin was also abolished by pertussis toxin (1mg/L) completely. Melatonin (1mmol/L and 0.1nmol/L) increased the content of met-Enk of lymphocytes in 2-and 11-month-old mice, respectively (P<0.01), which was blocked by nifedipine (1 mmol/L). CONCLUSION: Melatonin exerted an effect on immune responses in mice of different months, which might be mediated by G protein-AC-cAMP signal transduction pathway and regulation of met-Enk level.

To study the effects of melatonin on primary rat cortico-hippocampal neurotoxicity induced by amyloid beta-peptide 25-35. METHODS: The neuronal mor-phology was observed by phase-contrast microscopy. The iw.urotoxieity was quantitatively estimated by measur-ing laclate duhydrogenase (LDH) released into the culture medium from the damaged neurons. The neuronal metabolic state was quantified by the reduction of 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazo1ium bromide (MTr). RESULTS: Treatment ofprimary rat cortico-hipocampal neuonns with amyloid beta-peptide 25-35 (20 μmol/L) for 24h caused a significant decrease in neurocyte viability (P<0.01, compared with control). Melatonin (1 or 10 μmol/L) reduced the neurotoxicity induced by amyloid beta-peptidu 25-35. CONCLU-SION: Amyloid beta-peptide 25-35 could exert direct cytotoxicity on rat cortico-hippocampal neurocytes and melatonin concerdration-dependently rescued cultured neurons from exposure to amyloid beta-peptide 25-35 induced injury.