Anti-/Pro-Oxidants Stimulate Thyroid Hormone Effects on Amphibian Metamorphosis: Modulation through Neurotransmitter Turnover and Reactive Oxygen Status in a Tropical Frog, Clinotarsus curtipes (Jerdon)

Abstract

Reactive oxygen species (ROS) are known to influence molecular and biochemical processes and signal transduction pathways, affecting cellular proliferation, differentiation and death in a variety of organisms. Amphibian metamorphosis encompasses all these three events within a short span of time. In the frog Clinotarsus curtipes development is largely akin to the post-embryonic development in mammals, displaying increased levels of ROS under in vivo physiological conditions. Scavenging ROS with an antioxidant revealed a serendipitous finding of turning to a pro-oxidant and a novel thyroid hormone mimetic with potential effects on neurotransmitter functions. Further, confirmatory studies, both conventional binding assays combined with in- silico approaches, revealed the ability of the compound to bind to human thyroid receptors thereby to mimic the thyroid hormone activity and thus function as potent endocrine disrupting chemical. Thus our study also cautions against the indiscriminate use of supplementary molecules without proper validation. Our studies on amphibian (Clinotarsus curtipes) development are valuable in examining the role of ROS in post embryonic development.