The role of thyroid hormone on phenylhydrazine hydrochloride mediated inhibitory effects on blood acetylcholinesterase: an in vivo and in vitro study.
A novel phenomenon of protective counteraction by thyroid hormone has been demonstrated in phenylhydrazine hydrochloride (PHH) induced insult on blood acetylcholinesterase (AChE, EC 3.1.1.7) activity, in both, in vivo and in vitro conditions. Injection of PHH (20 microg/g) to juvenile male rats for three consecutive days caused a 48% decrease (p < 0.001) in the total blood AChE activity on the third day (i.e. 24 h after injections for three consecutive days) in comparison to the control animals. Simultaneous injections of thyroxine (T4) 1 or 2 microg/g with PHH (20 microg/g) showed a recovery in AChE activity by 27% (p < 0.02) and 55% (p < 0.001), respectively, in comparison to the only PHH-injected animals. T4 at 1, 2 and 4 microg/g doses showed unchanged levels in comparison to the untreated controls. In our in vitro system, incubations of the RBCs in PHH (2 mM) containing medium also showed an inhibition of 44% (p < 0.001) of the RBC membrane AChE activity in comparison to the control conditions. A recovery of 23-81% of the enzyme activity was observed after simultaneous use of T4 (1 nM-100 nM) or T3 (0.1 nM-100 nM), or triiodothyroacetic acid (TRIAC) (100 nM) with PHH (2 mM) in a dose-dependent manner with a potency profile of T3 > T4 > TRIAC. Incubation of RBCs only with T4, T3, or TRIAC at 0.1-100 nM concentration did not cause any alteration in the membrane AChE activity in comparison to control conditions. Thus, thyroid hormone distinctly demonstrated a counteraction or protective nature of action on the PHH-induced inhibition of total blood and RBC membrane AChE activity.
Banerjee
Mitali
M
Department of Animal Physiology, Bose Institute, P-1/12 CIT Scheme VII M, Kolkata-700 054, West Bengal, India.
Ray
Arun K
AK
D000110:Acetylcholinesterase / Q000097:blood*; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000201:enzymology; D066298:In Vitro Techniques; D008297:Male; D010659:Phenylhydrazines / Q000494:pharmacology*; D051381:Rats; D013963:Thyroid Hormones / Q000502:physiology*
D002800:Cholinesterase Inhibitors; D010659:Phenylhydrazines; D013963:Thyroid Hormones; C030299:phenylhydrazine; D000110:Acetylcholinesterase