The new rhodium(II) complex Rh2(Form) (O2CCF3)2(H2O)2 (Form = N,N'-di-p-tolyl formamidinate) was evaluated for its toxicity on the rat and for its efficacy against two tumors of this animal: the Yoshida ascites sarcoma and the T8 sarcoma of Guérin. The rhodium(II) formamidinate shows very low toxicity: in fact 150 mg/kg (the highest quantity of drug soluble in 4 ml of dimenthyl sulfoxide) is not toxic for rats. We were unable to establish the lethal dose or the highest nontoxic dose since larger mounts of complex require a dose of dimethyl sulfoxide (DMSO) that is itself toxic and the compound is insoluble in other solvents such as water or Tween. Doses of rhodium(II) formamidinate, varying from 3 to 30 mg/kg, were administered once by i.p., i.v., i.m. and intratumor (i.t.) route from 1 to 7 days after i.p. injection of 10(6) Yoshida ascites sarcoma cells and subcutaneous (s.c.) implantation of approximately 300 mg (corresponding to 2-3 x 10(7) living tumor cells) of T8 sarcoma of Guérin. The compound is active when administered i.p. 24 hours after Yoshida ascites sarcoma at the smallest dose tested (3 mg/Kg), increasing the average life span of 62.3% and allowing the survival of 50% of the rats. It is also active when administered i.p. at the highest dose tested (30 mg/Kg) 7 days after tumor cell challenge, increasing the average life span in 43.8% and allowing survival in 20% of the rats; it is not active after i.v. or i.m administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of mycotoxins--citrinin, ochratoxin B, rubratoxin B, and zearalenol beta--that affected superoxide anion (O2-) production were studied on human neutrophils with regard to hypochlorous acid (HOCl) generation, nitric oxide (NO) formation, and chemotaxis of isolated cells. At the doses of 10(-8), 10(-6), 10(-4), or 10(-2) mg/mL, in stimulated cells the mycotoxins inhibited HOCl production proportionally to that of O2- because HOCl production is directly dependent on O2- generation. But unlike the others, zearalenol beta decreased HOCl production much more than one of O2-, indicating an effect also on myeloperoxidase secretion. All mycotoxins inhibited NO generation but only at the dose of 10(-2) mg/mL. Formyl-met-leu-phe-induced chemotaxis of neutrophils was deeply affected as well, as all mycotoxins at all doses used decreased it. All considered effects were not dose-dependent, likely connected to high variability of individual sensitivity to these compounds and because they already are present in blood introduced with foods. These activities of neutrophils confirm and extend the danger for immune systems by mycotoxins also in very small quantities, since the smaller concentrations we used are easily reachable in blood.

The antitumoral activity of some octahedral platinum(IV) and square-planar platinum(II) derivatives against Yoshida ascites tumor in the rat is reported. It is shown that only those octahedral platinum(IV) complexes which give active reduction products are active. These results support the hypothesis that the antitumor activity of octahedral complexes involves activation by in vivo reduction. Anticancer drugs functioning by this mechanism may be preferentially toxic to or may localize in hypoxic areas of tumors.

Engystol-N at the doses of 10(-4) and 10(-8) in isolated human leukocytes stimulates the superoxide anion generation by neutrophils and the cytokine(s) production by T lymphocytes. In whole blood the same concentrations of the drug produce the decrease of the superoxide anion generation of neutrophils, this inhibiting activity appears 6 h after the administration of the drug and persists only in presence of lymphocytes. Culture media of T lymphocytes treated with Engystol-N show the same inhibiting effect on superoxide anion generation by neutrophils. From these data it is possible to conclude that the drug stimulates the secretion of lymphokine(s) with inhibiting action on superoxide anion generation of neutrophils that prevail over the direct stimulating effect, confirming and extending the immunomodulatory ability of the drug.

Activity of Glutoxim, a sulfur-containing hexapeptide with immunomodulating effect on lymphocytes, was studied on human neutrophils. Commercial available agent containing the substance, Glutoxim, was used. At the doses of 1, 3, 6 or 100 microg/mL the drug stimulated the superoxide anion and hypochlorous acid generation in resting neutrophils but inhibited them in cells stimulated with zymosan or PMA. The only inhibiting effect was observed on nitric oxide production in LPS-stimulated RAW 264.7 cells. The drug also influenced neutrophil chemotaxis showing chemoattractant activity on cells and inhibiting fMLP-induced chemotaxis. These effects on neutrophils confirm and extend range of Glutoxim immunomodulating abilities.