Biomedical subjects

S Barone

Publications and source records attributed to S Barone.

58 records · Page 4Linked to original sources

PubMedDate not supplied

Effects of organophosphates on the visual system of rats.

The possibility that exposure to organophosphate insecticides can lead to ocular damage is suggested by Japanese studies from the 1960s and 1970s indicating that exposed humans developed chronic ocular degeneration, in addition to showing more commonly accepted effects of cholinesterase-inhibiting compounds. Other papers reported ocular lesions in laboratory animals treated with organophosphates. More recently, retinal degeneration following chronic organophosphate treatment has been reported to the Environmental Protection Agency by pesticide manufacturers in studies conducted in compliance with good laboratory practice regulations. Several factors, however, have prompted scepticism regarding organophosphate-induced ocular toxicity, including the widespread use of organophosphate compounds for both agricultural and ophthalmological practices without numerous additional reports of comparable ocular toxicity. We are developing a research program to address these issues involving electrophysiological, biochemical and histological investigations of rats treated with organophosphate insecticides. The research program is young, but early results are available. Notably, retinas from rats treated with a single subcutaneous injection of 100 mg kg-1 fenthion showed decreases in carbachol-stimulated release of inositol phosphate, an indicator of cholinergically-mediated intracellular second messenger systems. These effects persisted at least 56 days after fenthion administration. This could indicate several different toxicological actions, which are currently under investigation. It is concluded that the possible association between exposure to organophosphates and ocular toxicity cannot be dismissed, and that several important research issues need to be resolved.

Animals↗

PubMedDate not supplied

Neurotoxic effects of neonatal triethyltin (TET) exposure are exacerbated with aging.

Neonatal Long-Evans rats dosed with TET (5 mg/kg; IP) or saline on postnatal day (PND) 10 were examined across the life span for neural damage and performance on spatial learning tasks. A subset of rats were sacrificed to assess early damage with Nissl-staining, Timm's histochemistry, and glial fibrillary acidic protein (GFAP) immunohistochemistry 2, 7, or 14 days after dosing. Littermates were tested behaviorally in a T-maze spatial delayed alternation task on PND 23 or PND 90, and in a Morris water maze place learning task at 3, 12, or 24 months postdosing and then sacrificed for histological analysis. In neonatal rats, histological analysis indicated gliosis in discrete cortical regions, loss of Nissl-stained neurons in the hippocampal formation, entorhinal cortex and piriform cortex, and loss of Timm's staining in the entorhinal cortex. The behavioral assessment at PND 23 indicated a significant impairment in the T-maze. However, no significant impairments were observed in the T-maze at 3 months or the water maze at 3 or 12 months postdosing. At 24 months, TET-treated rats showed significant deficits in acquisition and retention of the water maze task compared with age-matched controls. Both groups of 24 months old rats were significantly impaired compared with young controls. At 24 months, there was a general age-related decrease in the optical density of Timm's staining in cortical regions (9%), compounded by a further decrease in the entorhinal cortex and outer molecular layer of the dentate gyrus of the hippocampus in TET treated rats (30%). These data indicate that early developmental exposure to an organometal resulted in morphological damage that was apparent behaviorally only during early postnatal development and with advanced aging.

Aging↗

PubMedDate not supplied

Alterations in flash evoked potentials (FEPs) in rats produced by 3,3'-iminodipropionitrile (IDPN).

3,3'-Iminodipropionitrile (IDPN) is a neurotoxicant that produces changes in flash evoked potentials (FEPs) 18 weeks after treatment. We examined dose- and time-related effects of IDPN on FEPs at earlier time points than previously studied (52). Adult male Long-Evans rats were given IDPN (0, 100, 200, 400 mg/kg/day x 3 days, i.p.) and FEPs were recorded 14 days later. IDPN (400 mg/kg/day) decreased the amplitudes of some of the "early" and "middle" FEP peaks (n30 and N56), and increased the latencies of some early peaks (P21 and P46). A separate group of rats was treated with IDPN (0 or 400 mg/kg/day x 3 days, i.p.) and FEPs were recorded 1, 3, 7, 14, and 35 days later. The latencies of of all portions of FEPs were increased by IDPN, with maximal changes occurring at 7 and/or 14 days. The amplitude of the middle portions of FEPs (peaks N56, P63, N70, P90) were altered as early as day 3, and some changes were observed up to day 14. In contrast, the "late" portion of FEPs (peak N160) was affected at later times (days 14 and 35). Corneal opacities were noted on days 3 and 7, but were largely reversible by day 14. In the time-course study, IDPN decreased colonic temperature on days 1, 3, 7, and 14. The present results suggest that IDPN alters both the early FEP peaks related to the initial afferent sensory volley, and cortical processing associated with the middle and later portions of FEPs.

Animals↗

PubMedDate not supplied

Vulnerable processes of nervous system development: a review of markers and methods.

The susceptibility of the developing nervous system to damage following exposure to environmental contaminants has been well recognized. More recently, from a regulatory perspective, an increased emphasis has been placed on the vulnerability of the developing nervous system to damage following pesticide exposure. The publication of the National Academy of Sciences (NAS) report on Pesticides in the Diets of Infants and Children (1995) and the passage of the Food Quality Protection Act (FQPA) and Safe Drinking Water Act (SDWA) amendments have significantly escalated the scientific debate regarding age-related susceptibility. Key concerns raised in the NAS report include the qualitative and quantitative differences that distinguish the developing nervous system from that of the adult. It was suggested that neurotoxicity testing on adult animals alone may not be predictive of these differences in susceptibility. The age-related susceptibility of the nervous system is compounded by the protracted period of time over which this complex organ system develops. This temporal vulnerability spans the embryonic, fetal, infant, and adolescent periods. Normal development of the nervous system requires the concomitant and coordinated ontogeny of proliferation, migration, differentiation, synaptogenesis, gliogenesis, myelination and apoptosis to occur in a temporally- and regionally-dependent manner. Perturbations of these processes during development can result in long-term irreversible consequences that affect the structure and function of the nervous system and could account for qualitative differences in age-related susceptibility of the developing nervous system as compared to the adult nervous system. A discussion of developmental milestones and the relevance of transient effects on developmental endpoints are presented. Transient effects following developmental perturbations can be missed or dismissed depending on the experimental design or screening strategy employed. This subject is discussed in light of scientific uncertainties regarding perturbation-induced compensation in the developing nervous system. Thus, utilization of age-appropriate tests of these developmental processes may improve the detection and reduce uncertainty about the nature of adverse effects following developmental exposure to environmental neurotoxicants.

Animals↗