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Prevention of postasphyxia electroretinal dysfunction with a pyridoxal hydrazone
M Bhattacharya1, P Ponka, P Hardy
1Department of Physiology, McGill University, Montreal, Canada.
Insights
Pyridoxal isonicotinoyl hydrazone (PIH) effectively protects newborn piglet retinas from oxidative stress and visual damage caused by asphyxia-reoxygenation. Unlike deferoxamine, PIH preserves retinal function without adverse effects.
Area of Science:
- Neonatal ophthalmology
- Neuroscience
- Toxicology
Background:
- Newborn retinas are vulnerable to oxidative damage, leading to vision problems.
- Asphyxia-reoxygenation is a common cause of oxidative stress in newborns.
- Iron chelators are investigated for potential protective effects against retinal damage.
Purpose of the Study:
- To compare the efficacy of two iron chelators, deferoxamine and pyridoxal isonicotinoyl hydrazone (PIH), in protecting newborn piglet retinas from asphyxia-reoxygenation injury.
- To evaluate the impact of these chelators on retinal peroxidation and electrophysiological function.
Main Methods:
- Newborn pigs (1-3 days old) were intravenously treated with saline, deferoxamine, or PIH.
- Scotopic and photopic electroretinograms (ERGs) were recorded before and after treatment and asphyxia-reoxygenation.
- Retinal malondialdehyde (MDA) and hydroperoxide levels were measured as indices of peroxidation.
Main Results:
- Asphyxia-reoxygenation significantly increased retinal peroxidation (MDA, hydroperoxides) and impaired ERG function in saline-treated piglets.
- Both deferoxamine and PIH inhibited the increase in retinal peroxidation.
- Only PIH effectively prevented the post-asphyxia-reoxygenation changes in ERG amplitudes and implicit times, while deferoxamine negatively impacted pre-asphyxia ERG function.
Conclusions:
- Pyridoxal isonicotinoyl hydrazone (PIH) demonstrates superior efficacy in protecting the newborn retina from oxidative stress-induced electrophysiological alterations compared to deferoxamine.
- PIH effectively inhibits peroxidation and preserves retinal function following asphyxia-reoxygenation insults.
- PIH represents a promising alternative to deferoxamine for managing oxidative stress-related retinal injury in newborns.
Abstract:
The newborn retina is particularly sensitive and frequently subjected to peroxidative stresses that result in visual sequelae. We compared two iron chelators, deferoxamine and a newer compound, pyridoxal isonicotinoyl hydrazone (PIH), in protecting the retina of newborn pigs (1-3 d old) from asphyxia-reoxygenation insults. Animals were treated IV with either saline, deferoxamine 15.2 mumol/kg (10 mg/kg) or PIH 34.8 mumol/kg (10 mg/kg); n = 10 in each treatment group. Scotopic and photopic electroretinograms (ERG) were recorded before and 40 min after drug treatment as well as 45 min following a 5-min period of asphyxia by interrupting ventilation. In separate animals the indices of peroxidation, malondialdehyde (MDA: TBARS) and hydroperoxides, were measured in retina at the same times. In saline-treated animals, there was a marked increase in MDA and hydroperoxide concentrations in the retina following the asphyxia-reoxygenation period. This was associated with a decrease in the a- (photoreceptor generated) and b-wave (generated by Müller and bipolar cells) amplitudes measured under photopic (cone-mediated response) and scotopic (rod-mediated response) conditions, and an increase in their implicit times. PIH and deferoxamine prevented the postasphyxial increase in MDA and hydroperoxides. However, only PIH prevented the postasphyxial changes in a- and b-wave amplitudes and implicit times, whereas deferoxamine markedly altered the preasphyxial ERG and provided only partial postasphyxial protection simply to the retinal outer segment. Our findings indicate that the iron chelator PIH effectively inhibits peroxidation and retinal electrophysiological alterations secondary to asphyxia-reoxygenation-induced oxidative stresses to newborn animals, whereas deferoxamine adversely affects retinal function; hence, PIH may be a preferred alternative to deferoxamine.