Effects of dietary aflatoxin on the hepatic expression of apoptosis genes in growing barrows1

Rustemeyer, S. M.; Lamberson, W. R.; Ledoux, D. R.; Wells, Kevin D.; Austin, Kathy J.; Cammack, K. M.

doi:10.2527/jas.2010-3473

Cited by 39 publications

(36 citation statements)

References 37 publications

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“…RNA-seq procedures occurred at the University of Missouri DNA Core and are described in more detail elsewhere [34]. Briefly, following cDNA library construction, samples were loaded onto a flow cell where clusters of each oligo were replicated.…”

Section: Methodsmentioning

confidence: 99%

Herbal adaptogens combined with protein fractions from bovine colostrum and hen egg yolk reduce liver TNF-α expression and protein carbonylation in Western diet feeding in rats

Mobley

Toedebusch

Cm³

et al. 2014

Nutr Metab (Lond)

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BackgroundWe examined if a purported anti-inflammatory supplement (AF) abrogated Western-diet (WD)-induced liver pathology in rats. AF contained: 1) protein concentrates from bovine colostrum and avian egg yolk; 2) herbal adaptogens and antioxidants; and 3) acetyl-L-carnitine.MethodsNine month-old male Brown Norway rats were allowed ad libitum access to WD for 41–43 days and randomly assigned to WD + AF feeding twice daily for the last 31–33 days (n = 8), or WD and water-placebo feeding twice daily for the last 31–33 days (n = 8). Rats fed a low-fat/low-sucrose diet (CTL, n = 6) for 41–43 days and administered a water-placebo twice daily for the last 31–33 days were also studied. Twenty-four hours following the last gavage-feed, liver samples were analyzed for: a) select mRNAs (via RT-PCR) as well as genome-wide mRNA expression patterns (via RNA-seq); b) lipid deposition; and, c) protein carbonyl and total antioxidant capacity (TAC). Serum was also examined for TAC, 8-isoprostane and clinical chemistry markers.ResultsWD + AF rats experienced a reduction in liver Tnf-α mRNA (-2.8-fold, p < 0.01). Serum and liver TAC was lower in WD + AF versus WD and CTL rats (p < 0.05), likely due to exogenous antioxidant ingredients provided through AF as evidenced by a tendency for mitochondrial SOD2 mRNA to increase in WD + AF versus CTL rats (p = 0.07). Liver fat deposition nor liver protein carbonyl content differed between WD + AF versus WD rats, although liver protein carbonyls tended to be lower in WD + AF versus CTL rats (p = 0.08). RNA-seq revealed that 19 liver mRNAs differed between WD + AF versus WD when both groups were compared with CTL rats (+/- 1.5-fold, p < 0.01). Bioinformatics suggest that AF prevented WD-induced alterations in select genes related to the transport and metabolism of carbohydrates in favor of select genes related to lipid transport and metabolism. Finally, serum clinical safety markers and liver pathology (via lesion counting) suggests that chronic consumption of AF was well tolerated.ConclusionsAF supplementation elicits select metabolic, anti-inflammatory, and anti-oxidant properties which was in spite of WD feeding and persisted up to 24 hours after receiving a final dose.

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Section: Methodsmentioning

confidence: 99%

Herbal adaptogens combined with protein fractions from bovine colostrum and hen egg yolk reduce liver TNF-α expression and protein carbonylation in Western diet feeding in rats

Mobley

Toedebusch

Cm³

et al. 2014

Nutr Metab (Lond)

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“…For example, E2F transcription factor 1 (E2F1) and many genes downstream of E2F1 were up-regulated by AFB1 exposure; E2F1 regulates DNA replication and apoptosis, and could contribute to carcinogenesis [221]. Aflatoxicosis in pigs affects expression of many of the same pathways, with greatest effects on metabolism, cell cycle, DNA damage responses and apoptotic processes in one study [239] and on protein degradation, metabolism, apoptosis, and immune responses in another [227]. Hepatocellular carcinomas from AFB1-exposed rainbow trout showed changes in cell cycle, metabolism, immune and acute phase response genes when compared to adjacent non-cancerous liver tissue [228].…”

Section: Moving Towards Transcriptomicsmentioning

confidence: 99%

“…Hepatocellular carcinomas from AFB1-exposed rainbow trout showed changes in cell cycle, metabolism, immune and acute phase response genes when compared to adjacent non-cancerous liver tissue [228]. Two of these studies utilized high throughput RNA sequencing (RNA-seq), rather than microarrays, to characterize transcriptome changes after AFB1 exposure [221,239].…”

Section: Moving Towards Transcriptomicsmentioning

confidence: 99%

Aflatoxicosis: Lessons from Toxicity and Responses to Aflatoxin B1 in Poultry

2015

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This review is a comprehensive introduction to the effects of poultry exposure to the toxic and carcinogenic mycotoxin aflatoxin B1 (AFB1). The relationship between AFB1 sensitivity and metabolism, major direct and indirect effects of AFB1, recent studies of gene expression and transcriptome responses to exposure, and mitigation strategies to reduce toxicity are discussed. Exposure to AFB1 primarily occurs by consumption of contaminated corn, grain or other feed components. Low levels of residual AFB1 in poultry feeds can cause reduction in growth, feed conversion, egg production, and compromised immune functions, resulting in significant economic costs to producers. Thus, AFB1 acts as a "force multiplier" synergizing the adverse effects of microbial pathogens and other agents, and factors detrimental to poultry health. Domestic turkeys (Meleagris gallopavo) are one of the most sensitive animals known to AFB1 due, in large part, to a combination of efficient hepatic bioactivation by cytochromes P450 1A5 and 3A37, and deficient hepatic glutathione-S-transferase (GST)-mediated detoxification. Because of their sensitivity, turkeys are a good model to investigate chemopreventive treatments and feed additives for their ability to reduce AFB1 toxicity. Transcriptome analysis (RNA-seq) of turkey poults (liver and spleen) has identified AFB1-induced gene expression changes in pathways of apoptosis, carcinogenesis, lipid regulation, antimicrobial activity, cytotoxicity and antigen presentation. Current research focuses on further identifying the molecular mechanisms OPEN ACCESSAgriculture 2015, 5 743 underlying AFB1 toxicity with the goal of reducing aflatoxicosis and improving poultry health.

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“…RNAseq procedures occurred at the University of Missouri DNA Core and are described in more detail elsewhere (39). Briefly, following cDNA library construction, samples were loaded into flowcell where clusters of each oligo were replicated.…”

Section: Nac Rna Isolation From G8 Hvr and Lvr Nonrunners And Cdna LImentioning

confidence: 99%

Phenotypic and molecular differences between rats selectively bred to voluntarily run high vs. low nightly distances

Roberts

Brown

Company

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

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Brown M, Booth FW. Phenotypic and molecular differences between rats selectively bred to voluntarily run high vs. low nightly distances. Am J Physiol Regul Integr Comp Physiol 304: R1024-R1035, 2013. First published April 3, 2013 doi:10.1152/ajpregu.00581.2012.-The purpose of the present study was to partially phenotype male and female rats from generations 8 -10 (G8 -G10) that had been selectively bred to possess low (LVR) vs. high voluntary running (HVR) behavior. Over the first 6 days with wheels, 34-day-old G8 male and female LVRs ran shorter distances (P Ͻ 0.001), spent less time running (P Ͻ 0.001), and ran slower (P Ͻ 0.001) than their G8 male and female HVR counterparts, respectively. HVR and LVR lines consumed similar amounts of standard chow with or without wheels. No inherent difference existed in PGC-1␣ mRNA in the plantaris and soleus muscles of LVR and HVR nonrunners, although G8 LVR rats inherently possessed less NADH-positive superficial plantaris fibers compared with G8 HVR rats. While day 28 body mass tended to be greater in both sexes of G9 -G10 LVR nonrunners vs. G9 -G10 HVR nonrunners (P ϭ 0.06), body fat percentage was similar between lines. G9 -G10 HVRs had fat mass loss after 6 days of running compared with their prerunning values, while LVR did not lose or gain fat mass during the 6-day voluntary running period. RNA deep sequencing efforts in the nucleus accumbens showed only eight transcripts to be Ͼ1.5-fold differentially expressed between lines in HVR and LVR nonrunners. Interestingly, HVRs presented less Oprd1 mRNA, which ties in to potential differences in dopaminergic signaling between lines. This unique animal model provides further evidence as to how exercise may be mechanistically regulated. selective breeding; exercise; genes; nucleus accumbens; RNA-seq APPROXIMATELY 97% OF US adults and 92% of adolescents are not meeting US daily physical activity guidelines for 30 and 60 min, respectively (44). The clinical significance of lack of sufficient daily physical activity is an increased prevalence of 35 chronic unhealthy conditions and premature death (5). Motivation, fitness, and genes are all associated with physical activity levels (4). Twin and family studies have shown that genetic factors contribute to variation in reported daily physical activity levels, with identical cotwins showing smaller intraindividual variation than nontwins (see Ref. 4 for references).Animal studies also suggest that brain mechanisms affect the quantity of daily voluntary running (14,21,22,36,38).One approach to obtain genetic information on genes and physical activity has been to employ a selective breeding model of physical activity in rodents. According to Rhodes et al. (35), selective breeding is a "powerful alternative" compared with knockout models in studying genotype-phenotype interactions, given that multiple genes contribute to complex phenotypes. Swallow et al. (42) have phenotyped their 10th generation of mice selected for the highest revolutions per day of wheel running, these being ...

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Effects of dietary aflatoxin on the hepatic expression of apoptosis genes in growing barrows1

Cited by 39 publications

References 37 publications

Herbal adaptogens combined with protein fractions from bovine colostrum and hen egg yolk reduce liver TNF-α expression and protein carbonylation in Western diet feeding in rats

Herbal adaptogens combined with protein fractions from bovine colostrum and hen egg yolk reduce liver TNF-α expression and protein carbonylation in Western diet feeding in rats

Aflatoxicosis: Lessons from Toxicity and Responses to Aflatoxin B1 in Poultry

Phenotypic and molecular differences between rats selectively bred to voluntarily run high vs. low nightly distances

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