Toxic effects of putrescine in rat brain: Polyamines can be involved in the action of excitotoxins

Summary After treatment with putrescine (PUT) 200 mg/kg, i.p., male rats displayed a behavioural pattern that included wet dog shakes and motor inco-ordination. The concentration of PUT in the brain paralleled the severity of clinical signs. Histological examination showed the presence of perivascular edema and moderate spongiosis. These biochemical and histological features were present 2 h after treatment. At 24 h PUT levels in frontal cortex decreased but the histological status of brain tissue remained. Pretreatment with hyperosmolal glycerol did not modify the effect of PUT on the brain content of polyamine or the histological condition at 2 h. These results support a neurotoxic role for putrescine. Such effects were similar to those of kainic acid at convulsant doses, suggesting a role for putrescine in the action of this excitotoxin.     

Leishmania spp.: effect of inhibitors on growth and on polyamine and macromolecular syntheses

Ethidium bromide, pentamidine isethionate, and MGBG [methylglyoxal-bis (guanylhydrazone)] inhibited the uptake of radioactive putrescine by leishmanial (Leishmania spp.; Leishmania tropica major; Leishmania mexicana; Leishmania donovani) promastigotes and interfered with their polyamine synthesis. Inhibition was apparent as early as 1 hr after adding these drugs to the parasites at growth-inhibiting concentrations. Ethidium bromide also inhibited the incorporation of radioactive uracil into leishmanial RNA at growth-inhibiting concentrations, while DNA synthesis was inhibited by ethidium bromide at high concentrations after a lag period. MGBG inhibited the synthesis of leishmanial DNA and RNA at growth-inhibiting concentrations.