Document Type

Thesis

Date of Award

5-2014

School/College

College of Science, Engineering, and Technology (COSET)

Degree Name

MS in Environmental Toxicology

First Advisor

Dr. Momoh Yakubu

Abstract

y-hexachlorocyclohexane (g-HCH, lindane) is a halogenated organic insecticide used worldwide. Lindane is a persistent organic environmental pollutant and it can easily volatilize from water and soil into air and be transported long distances by natural processes. It is used as a scabicide, pediculicide, and ectoparasitic agent. Accumulation of lindane and its metabolites within the body could lead to serious neurological problems. The ingestion of these toxins has been speculated to be involved in diseases ranging from neurodegenerative disorders to cancer. Insecticides could be an initiating factor of atherosclerotic damage and inflammatory disruption of endothelial cell regulation of vascular smooth muscle. We examined the- effects of daily ingestion of lindane on vascular reactivity and the cellular mechanisms involved in the dysregulation of vascular function. Sprague Dawley rats (n=10) received 0.2mL of 17.6 mg/Kg; 115 of LDsoor vehicle (corn oil) oral gavage for 2 or 4 weeks and aortic ring explants' responses to phenylephrine (PE; 10-8 - 10-4 M)-induced contraction and relaxations by acetylcholine (ACh, 10-8 - 10-3 M) were determined. Both PE- and ACh-induced responses were significantly attenuated compared to control (p<0.05). To determine the mechanism(s) behind lindane-induced attenuation of vascular 2 signaling responses to PE and ACh, we investigated the effects of lindane (10-6- 10-3 M) on GPCR- Gaq mediated Ca2+ release from a non-excitable CHO-cell line stably expressing mACh1 GPCR in response to carbachol (10-8 - 10-3 M). Ca2+ signaling was measured by the ratiometric fluorescent Ca2+-indicator dye Fura-2AM. 18cubation of CHO-cell with 250 mM of lindane disrupted Ca2+ signaling to mACh1 activation by carbachol sensitizing Ca2+ release at the lower doses (10-8-10-6 M) and attenuating release at the higher doses (1 0􁪽5 -10-3 M) of carbachol. 24-Hours incubation of CHO-cell with lindane dose-dependently reduced the population of viable cell by 25% and 63% for 10-4 and 10-3 M of lindane respectively. In conclusion, daily ingestion of lindane adversely affects vascular responses to both ACh and PE, and these effects of lindane appeared to involve disruption of the GPCR Gaq mediated Ca2+ release.

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