Inhibition of Rat Testicular Nuclear Kinesins (<i>krp</i>2; KIFC5A) by Acrylamide as a Basis for Establishing a Genotoxicity Threshold

Friedman, Marvin A.; Zeiger, Errol; Marroni, Dennis; Sickles, Dale W.

doi:10.1021/jf703746f

Cited by 18 publications

(10 citation statements)

References 48 publications

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“…In addition to the oxidative stress mechanism of AA effect at the cellular level, inhibition of kinesin and dynein cytoskeletal motor protein families[ 35 ] induced by AA could explain the reproductive toxicity. [ 36 37 ] These findings were proved previously by Ali et al . [ 38 ] Lebda et al .,[ 13 ] and Al-Serwia and Ghoneim.…”

Section: Discussionsupporting

confidence: 74%

Histological and ultrastructure study of the testes of acrylamide exposed adult male albino rat and evaluation of the possible protective effect of Vitamin E intake

Hasanin

Sayed

Ghoneim

et al. 2018

J Microsc Ultrastruct

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Acrylamide (AA) is a hazardous unavoidable gonadal toxin. Hence, the aim of this study is to clarify its harmful effects on the testis of adult albino rat by light and electron microscope and to evaluate the possible role of Vitamin E (Vit E) in the prevention of such effects. Thirty-five adult male albino rats were enrolled in this study. They were divided into three groups: Group I (control); Group II (AA exposed), and Group III (AA and concomitant Vit E treated group). Animals of Groups II and III were further subdivided into two equal subgroups (each subgroup included five rats): (a) rats were sacrificed after 4 weeks and (b) rats were sacrificed after 6 weeks. The testes of each rat were dissected out, processed, and examined by Hematoxylin and Eosin, Periodic acid–Schiff and Mallory's trichrome stains as well as electron microscopic study. The study revealed that AA induces testicular damage at the histological and ultrastructural level in the form of degeneration and arrested spermatogenesis. Moreover, decreased seminiferous tubules diameters and epithelial height were detected. These changes are maximally improved in Vit E treated group. Hence, we could conclude that AA causes degenerative changes of the testes of albino rats and arrest of spermatogenesis. The AA-induced histological and ultrastructural changes of the testes could be explained by oxidative stress. These effects changes are proportional to the duration of exposure. Moreover, it could be concluded that Vitamin E has a protective role against AA-induced testicular damage by its antioxidant and anti-apoptotic effects.

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Section: Discussionsupporting

confidence: 74%

Histological and ultrastructure study of the testes of acrylamide exposed adult male albino rat and evaluation of the possible protective effect of Vitamin E intake

Hasanin

Sayed

Ghoneim

et al. 2018

J Microsc Ultrastruct

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“…AA is mutagenic in rats and mice [12] . This mutagenic profile does not fit the pattern of tumors observed in Fischer rats, as the specificity cannot be explained [27] , [52] , [65] , [74] . AA is a very weak carcinogen and mutagen [74] .…”

Section: Introductionmentioning

confidence: 62%

“…Kinesins have been demonstrated to be direct targets for AA and glycidamide [27] , [53] , [66] . While different kinesins were studied than the three upregulated in the current study, the fact that the activity of KIFC5A and KRP2, representative of two different kinesin families, could be inhibited by relatively low concentrations of AA or glycidamide (range 100–5 mM for 60–80% inhibition), suggests that the entire family may be vulnerable [66] , leading to cell division defects and potential carcinogenicity.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomics analysis and hormonal changes of male and female neonatal rats treated chronically with a low dose of acrylamide in their drinking water

Collí-Dulá

Friedman

Hansen³

et al. 2016

Toxicology Reports

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Acrylamide is known to produce follicular cell tumors of the thyroid in rats. RccHan Wistar rats were exposed in utero to a carcinogenic dose of acrylamide (3 mg/Kg bw/day) from gestation day 6 to delivery and then through their drinking water to postnatal day 35. In order to identify potential mechanisms of carcinogenesis in the thyroid glands, we used a transcriptomics approach. Thyroid glands were collected from male pups at 10 PM and female pups at 10 AM or 10 PM in order to establish whether active exposure to acrylamide influenced gene expression patterns or pathways that could be related to carcinogenesis. While all animals exposed to acrylamide showed changes in expected target pathways related to carcinogenesis such as DNA repair, DNA replication, chromosome segregation, among others; animals that were sacrificed while actively drinking acrylamide-laced water during their active period at night showed increased changes in pathways related to oxidative stress, detoxification pathways, metabolism, and activation of checkpoint pathways, among others. In addition, thyroid hormones, triiodothyronine (T3) and thyroxine (T4), were increased in acrylamide-treated rats sampled at night, but not in quiescent animals when compared to controls. The data clearly indicate that time of day for sample collection is critical to identifying molecular pathways that are altered by the exposures. These results suggest that carcinogenesis in the thyroids of acrylamide treated rats may ensue from several different mechanisms such as hormonal changes and oxidative stress and not only from direct genotoxicity, as has been assumed to date.

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“…The inhibition of some members of the kinesin and dynein cytoskeletal motor protein families may be the common site of action of ACR and GA, which could explain both neurotoxicity and male reproductive toxicity observed in animals (23). …”

Section: Discussionmentioning

confidence: 99%

Effects of Lipoic Acid on Acrylamide Induced Testicular Damage

2014

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Introduction:Acrylamide is very toxic to various organs and associated with significant increase of oxidative stress and depletion of antioxidants. Alpha-lipoic acid enhances cellular antioxidant defense capacity, thereby protecting cells from oxidative stress.Aim of the study:This study aimed to evaluate the protective role of alpha-lipoic acid on the oxidative damage induced by acrylamide in testicular and epididymal tissues.Material and methods:Forty adult male rats were divided into four groups (10 rats each). Control group; acrylamide treated group administered acrylamide 0.05% (w/v) in drinking water for 21 days; alpha-lipoic acid group received basal diet supplemented with 1% alpha-lipoic acid and forth group was exposed to acrylamide and treated with alpha-lipoic acid at the same doses and treatment regimen mentioned before.Results:The administration of acrylamide resulted in significant elevation in testicular and epididymal malondialdehyde level (MDA) and significant reduction in the level of reduced glutathione (GSH) and the activities of glutathione-S-transferase (GST), glutathione peroxidase (GPX) and glutathione reductase (GR). Also, acrylamide significantly reduced serum total testosterone and progesterone but increased estradiol (E2) levels. Treatment with alpha-lipoic acid prior to acrylamide induced protective effects and attenuated these biochemical changes.Conclusion:Alpha-lipoic acid has been shown to possess antioxidant properties offering promising efficacy against oxidative stress induced by acrylamide administration.

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Inhibition of Rat Testicular Nuclear Kinesins (krp2; KIFC5A) by Acrylamide as a Basis for Establishing a Genotoxicity Threshold

Cited by 18 publications

References 48 publications

Histological and ultrastructure study of the testes of acrylamide exposed adult male albino rat and evaluation of the possible protective effect of Vitamin E intake

Histological and ultrastructure study of the testes of acrylamide exposed adult male albino rat and evaluation of the possible protective effect of Vitamin E intake

Transcriptomics analysis and hormonal changes of male and female neonatal rats treated chronically with a low dose of acrylamide in their drinking water

Effects of Lipoic Acid on Acrylamide Induced Testicular Damage

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