Protective effect of pirenoxine and U74389F on induced lipid peroxidation in mammalian lenses. An in vitro, ex vivo and in vivo study

Oxidative stress is believed to be involved in cataract development. The pr otective effect of the xanthomatine derivative, pirenoxine, and the 21-amin osteroid U74389F on oxidative insult in mammalian lenses was evaluated in v itro, ex vivo and in vivo. In vitro pirenoxine and U74389F inhibited lipid peroxidation induced by iron or haemoglobin in guinea-pig homogenate lens o r whole lenses. Both compounds produced the same effect when lens oxidation was induced by superoxide producing system such as xanthine/xanthine oxida se or fMLP stimulated macrophages. In all the in vitro experiments, the val ues of biochemical lipid peroxidation markers, such as lipid hydroperoxides or thiobarbituric reactant substances, fell to the basal values with the a ddition of either pirenoxine (10(-5) M) or U74389F (10(-5) M). When two dro ps (60 mu l) of the above molecular solutions (0.005 and 0.012 % in saline respectively) were instilled in rabbit eyes (every hour for 8 hours over 2 days), the extracted lenses appeared to have better defences against an in vitro iron-induced lipid peroxidation, as shown by the values of conjugated dienes and lipid soluble fluorescent substances. These values also proved to be significantly lower when the same parameters were assayed in lenses f rom eyes where a lipid peroxidation was induced in vivo by haemoglobin or D iquat intravitreal injection followed by instillations of pirenoxine sodium salt or U74389F solutions (2 drops of about 60 mu l every hour for 8 hours over 4 day) administered topically. Polarographic and chronocoulometric me asurements were also performed in order to investigate the action mechanism s of both compounds. Experimental data indicate that the pirenoxine sodium salt and U74389F may be considered effective tools for rejecting an oxidati ve attack on the lenses, which can (C) 1999 Academic Press.