Inhibition of Creatine Kinase Activity in Rat Brain by Methyl Bromide Gas

Abstract

Rats were exposed to 290 or 495 ppm methyl bromide gas for 6 h/ day, 3 times/ wk for 4 to 8 wk. Creatine kinase ( CK) , aspartate aminotransferase ( ASAT) , and lactate dehydrogenase ( LDH) activities and bromide ion concentrations were measured in eight regions of the brain. Methyl bromide gas inhibited CK activities in all regions of the brain, though the inhibition tended to be smallest in the cerebellum ( hemisphere and vermis) and largest in the brainstem ( hypothalamus, midbrain, and medulla oblongata) . The dose of methyl bromide to inhibit CK activities was lower than that to damage the central nervous system histologically. No inhibition of ASAT or LDH activities was seen except for a slight inhibition of these in striatum. Inhibition of CK activities did not increase clearly on increasing dose ( 290 to 495 ppm) or on prolonging exposure period ( 4 to 8 wk) . Although 50% recovery of CK activities and the half-life of bromide ion agreed well in the medulla oblongata, changes in CK activities and bromide ion concentrations did not correlate otherwise. Thus, inhibition of CK activities in brain appears to be a sensitive indicator of methyl bromide intoxication, and may be related to genesis of its neurotoxicity. The inhibition seems to be caused by methyl bromide itself rather than by bromide ion. When effects on enzyme activities in brain homogenate were examined in vitro by bubbling with methyl bromide gas, CK inhibition was seen within 15 s of exposure. Dithiothreitol suppressed the CK inhibition, whereas N-acetylcysteine did not. These observations suggest that methyl bromide may attack sites in the CK molecule different from those attacked by ethylene oxide or acrylamide.

How unclogging a sink can be lethal: case report of an accidental methyl bromide poisoning leading to a multiple organ failure

“…Another suggested mechanism is that methyl bromide rapidly inhibits creatine kinase activity in all regions of the brain and in other target organs. Creatine kinase is an enzyme catalyzing the conversion of adenosine triphosphate and creatine to adenosine diphosphate and phosphocreatine [22,23]. …”