Chemoprevention of acrylamide toxicity by antioxidative agents in rats—effective suppression of testicular toxicity by phenylethyl isothiocyanate

Abstract

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.

Pathological assessment of the nervous and male reproductive systems of rat offspring exposed maternally to acrylamide during the gestation and lactation periods - a preliminary study

“…In the present study, ACR-induced neurotoxicity in maternal animals was evident from 100 ppm on morphometric assessment of the sciatic nerves and cerebellar molecular layer, as previously reported (Lee et al, 2005;Woo et al, 2007). Dams given ACR at concentrations of ≥100 ppm exhibited depression of body weight and food and water consumption in a dose-dependent fashion.…”

“…In the cerebellar molecular layer, increase of dot-like SYPimmunoreactive structures was observed from 100 ppm as reported previously ( Fig. 3E and F; Lee et al, 2005;Woo et al, 2007). However, the distribution of SYP-positive neuromuscular junctions in skeletal muscle did not differ among the groups.…”

“…The highest dose was chosen since it is known to induce neurotoxicity within 4 weeks in adult male rats of the same strain used in the present study (Lee et al, 2005). Litters were culled randomly to preserve 8 pups, mostly 4 per sex per litter on PND 3.…”

“…In addition, to assess ACR-induced neurological deficits, animals were scored with respect to the appearance of gait abnormalities (Moser, 1991;Shell et al, 1992;Lee et al, 2005) by placing individual animals free in Plexiglas boxes (90 × 90 × 20 cm) for 3 min. Degrees of abnormality were classified into four categories: grade 1 as normal gait; grade 2 as slightly abnormal gait with slight degrees of ataxia, hopping gait, and foot splay; grade 3 as moderately abnormal gait with moderate degrees of ataxia, foot splay and limb abduction; grade 4 as severely affected gait, including inability to support the body weight as well as foot splay.…”

“…In humans, since exposure to ACR occurs through ingestion of food in general population, it is reasonable to examine toxic effects of such chemicals by oral administration through food or drinking water to experimental animals. In the present study, ACR was administered to maternal rats through drinking water with the dose levels in inducing histologically apparent neurotoxicity and testicular toxicity after 4 weeks administration in adult male SD rats in our previous studies (Lee et al, 2005;Woo et al, 2007).…”