Chemoprevention of acrylamide toxicity by antioxidative agents in rats--effective suppression of testicular toxicity by phenylethyl isothiocyanate.
The efficacies of N-acetylcysteine (NAC), phenylethyl isothiocyanate (PEITC), and 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ) at preventing the neurotoxicity and testicular toxicity of acrylamide (ACR) were investigated in rats. To this end, Sprague-Dawley males were given 0.02% ACR in drinking water, with or without 1% NAC, 0.5% PEITC or 0.1% HTHQ in the diet for four weeks. A group of untreated controls was also included in the study. All ACR-treated animals exhibited progressive neurotoxicity as judged by gait scores, and among the chemicals co-administered, only HTHQ caused any suppression by the end of the experiment, and this was slight. The severity of the neurotoxicity, as judged by axonal degeneration in the spinal gracile fasciculus and sciatic nerve (distal portion) and aberrant dot-like synaptophysin immunoreactivity, reflecting nerve terminal degeneration in the cerebellar molecular layer, was not clearly reduced by co-administration of HTHQ, NAC or PEITC either. ACR-induced sciatic nerve axon atrophy was marginally and non-significantly reduced by HTHQ. In contrast, in terms of ACR-induced testicular toxicity, exfoliation of spermatids into seminiferous lumen was clearly reduced by co-administered PEITC and was marginally reduced by co-administered HTHQ. These antioxidative agents may therefore reduce/prevent ACR-induced toxicity, at least in the testes.
Lee
Kyoung-Youl
KY
Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
Shibutani
Makoto
M
Kuroiwa
Keiko
K
Takagi
Hironori
H
Inoue
Kaoru
K
Nishikawa
Hiroshi
H
Miki
Tokutaro
T
Hirose
Masao
M
D020106:Acrylamide / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001369:Axons / Q000187:drug effects / Q000473:pathology; D001835:Body Weight / Q000187:drug effects; D002525:Cerebellar Cortex / Q000378:metabolism; D004326:Drinking / Q000187:drug effects; D005684:Gait / Q000187:drug effects; D007150:Immunohistochemistry; D017879:Isothiocyanates / Q000494:pharmacology*; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology; D009422:Nervous System Diseases / Q000139:chemically induced / Q000517:prevention & control; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D012584:Sciatic Nerve / Q000473:pathology; D013116:Spinal Cord / Q000473:pathology; D016708:Synaptophysin / Q000378:metabolism; D013733:Testicular Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D012668:Trigeminal Ganglion / Q000473:pathology
D000975:Antioxidants; D017879:Isothiocyanates; D016708:Synaptophysin; D020106:Acrylamide; C058305:phenethyl isothiocyanate