Acrylamide (AA) is a vinyl monomer that has many applications in chemical industries. The aim of this work was to assess the reproductive toxicity of AA and clarity its underlying mechanism of action in rat; in particular, whether AA or its reactive metabolite glycidamide is responsible for the majority of the noted adverse effects. Moreover, the protective effect of 5-aminosalicylic acid (5-ASA) against AA testicular and genotoxicity was investigated. Acrylamide gavaged at doses from 5-60mg/kg daily for 5 consecutive days caused dose- dependent toxicity. Light microscopy examination showed multinucleated giant cells and tubular atrophy in the testis. In addition, electron microscopy showed Leydig cell atrophy and Sertoli cell toxicity. Epididymal sperm count showed a significant reduction in caudal sperm count in particular at higher concentrations. Despite these microscopic effects on the testis, this work also showed that AA has no toxic effects on absolute or relative testis or cauda weight, and no toxic effect on seminiferous tubule diameter. Outside of the testis, COMET assay undertaken on peripheral blood leukocytes showed genotoxicity in the form of COMET cells with increased Tail moment, while ELISA of serum testosterone showed severe reduction in testosterone level after AA treatment, which was reversed by concomitant ASA treatment. ELISA of CYP2El showed a 2-fold higher concentration in control liver S9 when compared to control testis S9. Further, 5-ASA (50mg/kg) induced the level of liver CYP2El, potentially increasing AA metabolism and clearance; this induction was accompanied by an improvement of testicular pathology and reduction in COMET Tail moments. Together, these data are consistent with AA being the main causative agent responsible for the toxicity noted in the testis and genotoxicity in blood. Moreover, 5-ASA could potentially offer a protective mechanism against AA- mediated toxicity, by increasing AA clearance. In conclusion, at the used dose, AA caused toxic effects in male rat that can be reduced by concomitant treatment with 5-ASA, which might be considered as an antidote to AA toxicity in victims of AA poisoning.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:583321 |
| Date | January 2012 |
| Creators | Rajeh, Nisreen A. |
| Publisher | University of Surrey |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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