Arachidonic acid (AA)-induced cytotoxicity was evaluated in leukocytes: the human leukemia cell lines HL-60, Jurkat and Raji and in rat lymphocytes. Such cytotoxicity was dose- and time-dependent. At concentrations below 5 microM, AA was not toxic; at 10-400 microM, AA induced apoptosis and at concentrations beyond 400 microM, necrosis. The minimum exposure time to trigger cell death was of around 1 h, but the effect was increased by longer exposure times until 6-24 h. Apoptosis was morphologically characterized by a decrease in cell and nuclear volume, chromatin condensation and DNA fragmentation and the presence of lipid bodies, without changes in organelle integrity. Biochemically, AA-induced apoptosis was associated with internucleosomal fragmentation and caspase activation, evaluated by PARP cleavage and the use of a caspase inhibitor. Necrosis was characterized by increased cell volume, presence of loose chromatin, appearance of vacuoles, loss of membrane integrity and of the definition of organelles. The apoptotic effect of AA was studied as to oxidative-reductive imbalance and the participation of eicosanoids. Apoptotic AA treatment was accompanied by an increase in the quantity of thiobarbituric acid reactive substances (TBARS), low-level chemiluminescence and in the glutathione disulfide/reduced glutathione ratio, indicating oxidative stress. The addition of tocopherol, ascorbate, prostaglandin E2 and lipoxygenase inhibitors delayed cell death, whereas the inhibition of cyclooxygenase promoted AA-induced cell death. Cell treatment with AA was accompanied by increased cellular production of LTB4. AA, therefore, is cytotoxic at physiological and supraphysiological concentrations, causing apoptosis and necrosis. Cell treatment with apoptotic concentrations of AA involves oxidative stress and changes in eicosanoid biosynthesis.

The rhodium (II) complexes Rh2(tfa)4.2(tfac) and Rh2(tfacam) 4 (tfacam CF3CONH-,tfa CF3COO-, tfac CF3CONH2) were synthesized and characterized b) microanalysis and electronic and vibrational spectroscopies. Rhz(tfacam)4 was tested both in vitro (U937 and K562 human leukemia cells and Ehrlich ascitic tumor cells) and in vivo for cytostatic activity and lethal dose determination, respectively. This is the first rhodium tetra-amidate to have its biological activity evaluated. The LDs0 value for Rh2(tfacam)4 is of the same order as that of cisplatin, and it was verified that the rhodium complex usually needs lower doses than cisplatin to promote the same inhibitory effects.

Metformin reduced Walker-256 tumor development but not cachexia in obese rats. The reduction occurred independently of the correction of insulin resistance. Metformin increased the area of necrosis in tumor tissues, which may have contributed to the reduced tumor development.

1. Sodium warfarin, given by oral or by parenteral route, displays a pronounced anti-inflammatory effect in the formaldehyde and carrageenan induced rat paw edema. This effect becomes patent not only when the warfarin application precedes the local injection of the irritant substance (prophylactic effect), but also when it is given to animals with already developed inflammatory reactions (therapeutic effect). 2. The active doses of Na warfarin lie between 0.5 and 5.0 mg/kg. Smaller as well as higher doses show a reduced anti-inflammatory effect. 3. A marked anti-inflammatory effect can be noted already 90 min after drug injection at a still normal prothrombin level. 4. Vitamin K1 (phylloquinone), given by oral or parenteral route, in doses from 1.6 mg/kg upwards, shows a marked anti-inflammatory effect both in the prophylactic and the therapeutic rat paw test. Vitamin K3 is devoid of any anti-inflammatory activity. 5. The anti-inflammatory effect of both sodium warfarin and of vitamin K1 in rats, is not interfered with by previous adrenalectomy.

No abstract