Acute and subchronic exposure of cyadox induced metabolic and transcriptomic disturbances in Wistar rats. (December 2022)

• Record Type: Journal Article
• Authors: Huang, Chongyang; Lei, Hehua; Liu, Chaoyang; Wang, Yulan
• Is Part Of: Toxicology. Volume 482(2022)
• Publication Date: 2022-12
• Subjects: Ac acute toxicity study -- C control -- L low-dose group -- M moderate-dose group -- H high-dose group -- U urine -- P plasma -- L liver -- Rc renal cortex -- Rm renal medulla -- 1H–13C HMBC 1H-13 C heteronuclear multiple bond correlation spectroscopy 1 H-13 C HSQC 1 H-13 C heteronuclear single quantum coherence spectroscopy -- 1H–1H COSY 1H–1H correlation spectroscopy -- 1–1 H JRES 1–1 H J-resolved spectroscopy -- 1H–1H TOCSY 1H–1H total correlation spectroscopy -- CPMG Carr-Purcell-Meiboom-Gill -- β-Ala β-Alanine -- β-HB β-hydroxybutyrate -- MA methylamine -- 2-HPPA 2-(4-hydroxy phenyl) propanoic acid -- 4-CG 4-cresol glucuronide -- 4-EG 4-ethylphenol glucuronide -- 6-HNA 6-Hydroxynicotinic acid -- ADP adenosine diphosphate -- ALB albumin -- Alln allantoin -- Ala alanine -- Ace acetate -- Acet acetone -- AKP alkaline phosphatase -- ALT alanine aminotransferase -- AMP adenosine monophosphate -- Asn asparagine -- Asp aspartic acid -- AST aspartate aminotransferase -- ATP adenosine triphosphate -- BA bile acid -- BTL betaine aldehyde -- Bet betaine -- BUN blood urea nitrogen -- Cho choline -- CHOL total cholesterol -- Cit citric acid -- Cre creatine -- CREA creatinine(serum) -- Crn creatinine(urine) -- CTP cytidine triphosphate -- CYP 450 Cytochrome P450 -- COA coenzyme A -- DB direct bilirubin -- DMA dimethylamine -- DMG dimethylglycine -- Dms dimethyl sulfone -- DNA deoxyribonucleic acid -- Fum fumarate -- Fa formate -- GGT gamma-glutamyltransferase -- Glc/GLC glucose -- Gln glutamine -- Glu glutamate -- Glua Glutarate -- Gly glycine -- Glyn glycogen -- GPC glycerophosphocholine -- GSSG oxidized glutathione -- Guo guanosine -- Hcy homocysteine -- Hip Hippurate -- His histidine -- Hyp hypoxanthine -- IDP inosine diphosphate -- Ile Isoleucine -- IMP inosine monophosphate -- Inds Indoxyl sulfate -- Ino inosine -- ITP inosine triphosphate -- Lac lactic acid -- Leu leucine -- Lys lysine -- Lip lipoproteins -- Mal malonate -- Man mannose -- MAPK mitogen-activated protein kinase -- Met methionine -- MG methylguanidine -- 3-HPPA 3-(3-hydroxyphenyl) propanoic acid -- NM nicotinamide -- NAD nicotinamide adenine dinucleotide -- NADP nicotinamide adenine dinucleotide phosphate -- NAG N-acetyl-glycoprotein -- NRN nicotinamide ribonucleotide -- NRNs nicotinamide ribonucleoside -- NMN N-methylnicotinamide -- NMR nuclear magnetic resonance -- OAG O-acetyl-glycoprotein -- O-PLS-DA orthogonal projection to latent structures discriminant analysis -- OsA oxalosuccinate -- PAG phenylacetylglycine -- PC phosphocholine -- PCA principal component analysis -- 2-pro 2-propanol -- Phe phenylalanine -- PLS-DA projection to latent structures discriminant analysis -- PPAR peroxisome proliferator-activated receptors -- PAA pantothenate -- COA ROS, reactive oxygen species -- SAM significance analysis of microarrays -- SAH S-adenosyl-Homocysteine -- SAMe S-adenosylmethionine -- Suc succinate -- SCD stearoyl-CoA desaturase -- SOD superoxide dismutase -- S-W6 the 6th week of the subchronic toxicity study -- S-W12 the 12th week of the subchronic toxicity study -- S-W14 the 14th week of the subchronic toxicity study -- Tau taurine -- TB total bilirubin -- TCA tricarboxylic acid -- TG triglyceride -- TMA trimethylamine -- TMAO trimethylamine-N-oxide -- TP total protein -- TSP sodium 3-trimethylsilyl-2, 2, 3, 3-tetradeuteropropionate -- Tyr tyrosine -- UDP uridine 5′-diphosphate -- UDP-GlcNAc UDPGN uridine diphosphate-N-acetylglucosamine -- UMP uridine 5′-monophosphate -- Ura uracil -- Urd uridine -- Val valine -- VEGF vascular endothelial growth factor -- α-ABA α-aminobutyrate -- α-HIA α-Hydroxyisovalerate -- α-KG α-ketoglutaric acid; NMR based Metabolomics -- Cyadox -- Transcriptomics -- Toxicity; Toxicology -- Periodicals; Chemicals -- Physiological effect -- Periodicals; 615.9005
• DOI: 10.1016/j.tox.2022.153367
• Languages: English
• ISSNs: 0300-483X

Abstract

Abstract: Cyadox, a potential antimicrobial growth promoter, has been widely studied and prospected to be used as an additive in livestock and poultry feed. Although high cyadox exposure has been reported to cause toxicity, the exact metabolic effects are not fully understood. Our study aim is to evaluate the metabolic effects of cyadox using comprehensive methods including serum clinical chemical test, histopathology analysis, metabolomics, and transcriptomics profile analysis. One single acute dosage over 7-day course and one subchronic 90-day dietary ingestion of cyadox intervention were conducted on the Wistar rats separately. Dose-dependent alterations were shown in the metabolism of the urine, kidney, plasma, and liver by metabolomics analysis. We further investigated gene expressions of the liver administered with high dose of cyadox for 12 weeks. Top sixty-six differentially expressed genes involved in the pathways, including xenobiotic (cyadox) metabolism, lipid metabolism, energy metabolism, nucleic acid metabolic process, inflammatory response, and response to the oxidative stress, which were in concordance with these metabolic alternations. Our study provided a comprehensive information on how cyadox modulates the metabolism and gene expressions, which is vital when considering the safe application of cyadox. Graphical Abstract: ga1