Background: The present study was designed to test the hypothesis that chronic very mild prenatal carbon monoxide (CO) exposure (25 parts per million) subverts the normal development of the rat cerebellar cortex. Studies at this chronic low CO exposure over the earliest periods of mammalian development have not been performed to date. Pregnant rats were exposed chronically to CO from gestational day E5 to E20. In the postnatal period, rat pups were grouped as follows: Group A: prenatal exposure to CO only; group B: prenatal exposure to CO then exposed to CO from postnatal day 5 (P5) to P20; group C: postnatal exposure only, from P5 to P20, and group D, controls (air without CO). At P20, immunocytochemical analyses of oxidative stress markers, and structural and functional proteins were assessed in the cerebellar cortex of the four groups. Quantitative real time PCR assays were performed for inducible (iNOS), neuronal (nNOS), and endothelial (eNOS) nitric oxide synthases.

Iron deficiency and chronic mild carbon monoxide (CO) exposure are nutritional and environmental problems that can be experienced simultaneously. We examined the effects of chronic mild CO exposure and iron availability on auditory development in the rat. We propose that chronic mild CO exposure creates an oxidative stress condition that impairs the spiral ganglion neurons. The CO-exposed rat pups had decreased neurofilament proteins and increased copper, zinc-superoxide dismutase (SOD1) in the spiral ganglion neurons. We conclude that the increased amount of SOD1 causes an increase in hydrogen peroxide production that allows the Fenton reaction to occur. This reaction uses both iron and hydrogen peroxide to generate hydroxyl radicals and leads to the development of oxidative stress that impairs neuronal integrity. However, rat pups with decreased iron and CO exposure (ARIDCO) exhibited in their cochlea an up-regulation of transferrin, whereas their expression of neurofilament proteins and SOD1 were similar to control. Consequently, reduced iron availability and the normal expression of SOD1 do not promote oxidative stress in the cochlea. By using basal c-Fos expression as a marker for cellular activation we found a significant reduction in c-Fos expression in the central nucleus of the inferior colliculus in iron-adequate rat pups exposed to CO. By contrast, rather than being reduced, c-Fos expression in the ARIDCO group is the same as for controls. We conclude that the cochlea of rat pups with normal iron availability is selectively affected by mild CO exposure, causing a chronic oxidative stress, whereas limiting iron availability ameliorates the effect caused by mild CO exposure by averting conditions that facilitate oxidative stress.

Highlights The venom protein-protein interactions in snake venom remain largely unknown. Y2H coupled with MD simulations was used to detect venom protein interactions. Venom PLA 2 s interact with themselves and Lys49 PLA 2 interacts with venom CRISP.

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