Pharmacology and toxicology of diphenyl diselenide in several biological models

The pharmacology of synthetic organoselenium compounds indicates that they can be used as antioxidants, enzyme inhibitors, neuroprotectors, anti-tumor and anti-infectious agents, and immunomodulators. In this review, we focus on the effects of diphenyl diselenide (DPDS) in various biological model organisms. DPDS possesses antioxidant activity, confirmed in several in vitro and in vivo systems, and thus has a protective effect against hepatic, renal and gastric injuries, in addition to its neuroprotective activity. The activity of the compound on the central nervous system has been studied since DPDS has lipophilic characteristics, increasing adenylyl cyclase activity and inhibiting glutamate and MK-801 binding to rat synaptic membranes. Systemic administration facilitates the formation of long-term object recognition memory in mice and has a protective effect against brain ischemia and on reserpine-induced orofacial dyskinesia in rats. On the other hand, DPDS may be toxic, mainly because of its interaction with thiol groups. In the yeast Saccharomyces cerevisiae, the molecule acts as a pro-oxidant by depleting free glutathione. Administration to mice during cadmium intoxication has the opposite effect, reducing oxidative stress in various tissues. DPDS is a potent inhibitor of d-aminolevulinate dehydratase and chronic exposure to high doses of this compound has central effects on mouse brain, as well as liver and renal toxicity. Genotoxicity of this compound has been assessed in bacteria, haploid and diploid yeast and in a tumor cell line.

Effects of industrial solvents on hearing and balance: a review.

Industrial hearing loss has generally been associated with noise exposure, but there is a growing awareness that industrial solvents can have an adverse effect on the auditory and vestibular systems in man. Both animal experiments and human studies point to an ototoxic effect of industrial solvents, as well as some central auditory and vestibular disturbances. This review examines the research from the last four decades in an attempt to get an overview of the available evidence. Research shows that industrial solvents are ototoxic in rats. The majority of the solvents studied cause a loss of auditory sensitivity in the mid-frequencies in rats, affecting outer hair cells in the order OHC 3 > OHC 2 > OHC 1 . Inner hair cells are generally unaffected. Spiral ganglion cells are most vulnerable to trichloroethylene. Simultaneous exposure to solvents and noise results in a synergistic effect; the pattern of trauma mirrors that due to solvent exposure rather than noise, but is more enhanced. There is a critical level when synergy occurs. The effects of solvents on the vestibular system are neurotoxic and influence the vestibulo-oculomotor system in both animals and humans; humans also present with problems in postural sway. There is a strong suggestion from human studies that solvents are ototoxic in man, but findings show that both the peripheral and central auditory pathways can be affected. Hearing losses can be in the high frequency region or can affect a wider range of frequencies. Hearing loss and balance disturbances can occur at levels below permitted levels of exposure. The synergistic effect of combined exposure to solvents and noise has also been noted in humans, resulting in greater hearing losses than would be expected from exposure to noise and solvents alone. The findings from both human and animal studies indicate that exposure to industrial solvents or to industrial solvents and noise can have an adverse effect on hearing and balance. The implications for industry and hearing conservation are far reaching.