Investigations on pesticide-induced endocrine disruption with special reference to biochemical alterations in adrenal cortex and their consequences

The present work was carried out to investigate (a) the impact of
organophosphorus insecticides (OPI) (acephate and monocrotophos) and
organochlorine insecticide (hexachlorocyclohexane; HCH) on adrenocortical
functions in rats by assessment of their effects on circulating levels of steroid
hormones and associated change in adrenals (b) consequences of their effects
on adrenocortical functions (c) toxic effects of OPI (those with potential to alter
adrenocortical functions in rats) against the nematode, Caenorhabditis elegans.
Our results clearly demonstrated that both OPI and HCH have the propensity to
modulate adrenocortical functions. OPI were found to cause hyperactivation of
adrenocortical functions characterized by hypercorticosteronemia and depletion
of adrenal cholesterol. HCH treatment caused decrease in circulating levels of
corticosterone. Under these experimental conditions, OPI elicited
hyperglycemia in rats with concomitant increase in liver gluconeogenesis
enzymes. Contrastingly, HCH caused decrease in blood glucose levels and
decrease in activities of key liver gluconeogenesis enzymes. Stressogenic and
hyperglycemic potential of monocrotophos were found to manifest as
simultaneous and independent consequences of AChE inhibition. Further
studies revealed that physiological significance of hypercorticosteronemia in
monocrotophos-treated rats was restricted to induction of liver tyrosine
aminotransferase, and not hyperglycemia. Our work shows that
monocrotophos-induced hyperglycemia is mediated by adrenergic mechanisms
and may involve assimilation of lactate in to glucose. Exposure of C. elegans to
sublethal concentrations of monocrotophos was associated with AChE
inhibition, paralysis and decrease in brood size. Pralidoxime and atropine were
able to rescue worms from paralyzing effects of monocrotophos, indicating role
of AChE inhibition in paralysis. Our work clearly demonstrated the effects of
OPI and HCH on adrenocortical functions and glucose homeostasis. Further, it
is clear that monocrotophos-induced hyperactivation of adrenal cortex and
hyperglycemia in rats and paralysis in C. elegans is mediated by AChE
inhibition.