Archives of Toxicology

, Volume 85, Issue 9, pp 1109–1120

Life stage-related differences in susceptibility to acrylamide-induced neural and testicular toxicity

  • Miwa Takahashi
  • Kaoru Inoue
  • Naoki Koyama
  • Midori Yoshida
  • Kaoru Irie
  • Tomomi Morikawa
  • Makoto Shibutani
  • Masamitsu Honma
  • Akiyoshi Nishikawa
Organ Toxicity and Mechanisms

Abstract

In order to assess age-dependence of susceptibility to acrylamide (ACR)-induced neural and testicular toxicity, 3- and 7-week-old male SD rats were given ACR at 0, 50, 100, or 200 ppm in the drinking water for 4 weeks, and the nervous and male reproductive systems were examined histopathologically. Testicular genotoxicity was evaluated with the comet assay and the micronucleus (MN) test. Glutathione S-transferase (GST) activity and glutathione (GSH) content in the liver and testis were also measured. In both young and adult animals, neurotoxicity was evident from 100 ppm and increased in proportion to ACR intake per body weight. In the testis, marked degeneration and exfoliation, mainly of spermatids, were observed from 100 ppm limited to young animals. The comet assay revealed ACR to significantly induce DNA damage from 100 ppm in both life stages, while MNs were found only in young rats from 100 ppm. The level of GST activity in the testis of young rats at the end of experiment was significantly lower than that of adult animals, regardless of the ACR treatment. There were no life stage-related differences in GSH contents in the liver and testis. These results suggest that susceptibility to neurotoxicity might not differ between young and adult rats when exposure levels are adjusted for body weight. Regarding testicular toxicity, young animals around puberty proved more susceptible than adult animals, possibly due to their lower level of testicular GST activity than that in adult animals.

Keywords

Acrylamide Age Susceptibility Neurotoxicity Testicular toxicity Rat 

References

  1. Burlinson B, Tice RR, Speit G, Agurell E, Brendler-Schwaab SY, Collins AR, Escobar P, Honma M, Kumaravel TS, Nakajima M, Sasaki YF, Thybaud V, Uno Y, Vasquez M, Hartmann A (2007) Fourth international workgroup on genotoxicity testing: results of the in vivo comet assay workgroup. Mutat Res 627:31–35PubMedGoogle Scholar
  2. Exon JH (2006) A review of the toxicology of acrylamide. J Toxicol Environ Health B Crit Rev 9:397–412PubMedCrossRefGoogle Scholar
  3. Friedman MA, Zeiger E, Marroni DE, Sickles DW (2008) Inhibition of rat testicular nuclear kinesins (krp2; KIFC5A) by acrylamide as a basis for establishing a genotoxicity threshold. J Agric Food Chem 56:6024–6030PubMedCrossRefGoogle Scholar
  4. Ishii Y, Okamura T, Inoue T, Tasaki M, Umemura T, Nishikawa A (2009) Dietary catechol causes increased oxidative DNA damage in the livers of mice treated with acetaminophen. Toxicology 263:93–99PubMedCrossRefGoogle Scholar
  5. Kaplan ML, Murphy SD (1972) Effect of acrylamide on rotarod performance and sciatic nerve—glucuronidase activity of rats. Toxicol Appl Pharmacol 22:259–268PubMedCrossRefGoogle Scholar
  6. Ko MH, Chen WP, Lin-Shiau SY, Hsieh ST (1999) Age-dependent acrylamide neurotoxicity in mice: morphology, physiology, and function. Exp Neurol 158:37–46PubMedCrossRefGoogle Scholar
  7. Lee KY, Shibutani M, Kuroiwa K, Takagi H, Inoue K, Nishikawa H, Miki T, Hirose M (2005) Chemoprevention of acrylamide toxicity by antioxidative agents in rats–effective suppression of testicular toxicity by phenylethyl isothiocyanate. Arch Toxicol 79:531–541PubMedCrossRefGoogle Scholar
  8. Moser VC (1991) Investigations of amitraz neurotoxicity in rats. IV. Assessment of toxicity syndrome using a functional observational battery. Fundam Appl Toxicol 17:7–16Google Scholar
  9. Papp S, Robaire B, Hermo L (1994) Developmental expression of the glutathione S-transferase Yo subunit in the rat testis and epididymis using light microscope immunocytochemistry. Anat Rec 240:345–357PubMedCrossRefGoogle Scholar
  10. Parzefall W (2008) Minireview on the toxicity of dietary acrylamide. Food Chem Toxicol 46:1360–1364PubMedCrossRefGoogle Scholar
  11. Peltola V, Huhtaniemi I, Ahotupa M (1992) Antioxidant enzyme activity in the maturing rat testis. J Androl 13:450–455PubMedGoogle Scholar
  12. Shell L, Rozum M, Jortner BS, Ehrich M (1992) Neurotoxicity of acrylamide and 2, 5-hexanedione in rats evaluated using a functional observational battery and pathological examination. Neurotoxicol Teratol 14:273–283PubMedCrossRefGoogle Scholar
  13. Sickles DW, Sperry AO, Testino A, Friedman M (2007) Acrylamide effects on kinesin-related proteins of the mitotic/meiotic spindle. Toxicol Appl Pharmacol 222:111–121PubMedCrossRefGoogle Scholar
  14. Suzuki K, Pfaff LD (1973) Acrylamide neuropathy in rats. An electron microscopic study of degeneration and regeneration. Acta Neuropathol 24:197–213Google Scholar
  15. Takahashi M, Shibutani M, Inoue K, Fujimoto H, Hirose M, Nishikawa A (2008) 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. J Toxicol Sci 33:11–24PubMedCrossRefGoogle Scholar
  16. Takahashi M, Shibutani M, Nakahigashi J, Sakaguchi N, Inoue K, Morikawa T, Yoshida M, Nishikawa A (2009) Limited lactational transfer of acrylamide to rat offspring on maternal oral administration during the gestation and lactation periods. Arch Toxicol 83:785–793PubMedCrossRefGoogle Scholar
  17. Tates AD, Dietrich AJJ, de Vogel N, Neuteboom I, Bos A (1983) A micronucleus method for detection of meiotic micronuclei in male germ cell of mammals. Mutat Res 121:131–138PubMedCrossRefGoogle Scholar
  18. Tice RR, Agurell E, Anderson D, Burlinson B, Hartmann A, Kobayashi H, Miyamae Y, Rojas Y, Ryu JC, Sasaki YF (2000) Single cell gel/comet assay: guidelines for in vitro and in vivo genetic toxicology testing. Environ Mol Mutagen 35:206–221PubMedCrossRefGoogle Scholar
  19. WHO/IPCS (2006) Summary and conclusions of the sixty-fourth meeting of the Joint FAO/WHO Expert Committee on Food Additives (JECFA) Rome, 8-17 February 2005. summary_report_64_final.pdf.Available from: http://www.who.int/ipcs/food/jecfa/summaries/en/i
  20. Yousef MI, El-Demerdash FM (2006) Acrylamide-induced oxidative stress and biochemical perturbations in rats. Toxicology 219:133–141PubMedCrossRefGoogle Scholar
  21. Zhang X, Cao J, Jiang L, Geng C, Zhong L (2009) Protective effect of hydroxytyrosol against acrylamide-induced cytotoxicity and DNA damage in HepG2 cells. Mutat Res 664:64–68PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Miwa Takahashi
    • 1
  • Kaoru Inoue
    • 1
  • Naoki Koyama
    • 2
  • Midori Yoshida
    • 1
  • Kaoru Irie
    • 1
  • Tomomi Morikawa
    • 1
  • Makoto Shibutani
    • 1
    • 3
  • Masamitsu Honma
    • 2
  • Akiyoshi Nishikawa
    • 1
  1. 1.Division of PathologyNational Institute of Health SciencesSetagaya-ku, TokyoJapan
  2. 2.Division of Genetics and MutagenesisNational Institute of Health SciencesSetagaya-ku, TokyoJapan
  3. 3.Laboratory of Veterinary PathologyTokyo University of Agriculture and TechnologyFuchu, TokyoJapan

Personalised recommendations