Environmental metabolite, 1, 2-diacetylbenzene, produces cytotoxicity in neuronal/glial cultures

Abstract

Background: A toxic solvent metabolite, 1,2-Diacetylbenzene (1,2-DAB) induces blue-purple discoloration of urine in humans and animals. Rats treated with 1,2-DAB, but not with its isomer 1,3-DAB, developed blue-purple discoloration of the brain and spinal cord. This work examines the toxicity of 1,2-DAB and underlying mechanism in neuronal and glial cells. Methods: The effect of 1,2-DAB was examined in primary neuronal culture, glial culture and slice/explant cultures. Results: 1,2-DAB but not 1,3-DAB depleted ATP level and induced cell damage in both neuronal and glial cultures with neurons being more susceptible to 1,2-DAB toxicity. 1,2-DAB also induced neurofilament aggregation in spinal cord slices. To further study the molecular mechanism, we used time-lapse video recording of neurons growing on dishes coated with patterned laminin to investigate the movement of mitochondria in axons. Actively outgrowing neurites retracted slowly and the proximal axonal transport of mitochondria gradually ceased within two hours after exposure to 1,2-DAB but not of 1,3-DAB. Conclusions:1,2-DAB decreased ATP levels, increased protein aggregation, inhibited mitochondria transport, and resulted in cell death.