Effects of a 28-day dietary co-exposure to melamine and cyanuric acid on the levels of serum microRNAs in male and female Fisher 344 rats

Abstract

We showed previously that a 28-day combined dietary exposure to melamine and cyanuric acid (MEL&CYA) induced kidney lesions in NCTR Fisher 344 (F344) rats. Histopathological changes were significant in females dosed with ≥240ppm MEL&CYA and in males dosed with ≥180ppm MEL&CYA; however, the nephrotoxicity biomarkers blood urea nitrogen (BUN) and serum creatinine (SCr) were increased only by ≥240ppm MEL&CYA. The serum miRNome has been reported to reflect toxicity of several organs, including the kidney. Here, we compared the dose-response of alterations in serum miRNAs to those of BUN, SCr, and kidney histopathology in rats co-exposed to MEL&CYA. The serum miRNome of male F344 rats dosed with 0, 180, or 240ppm MEL&CYA was screened using quantitative real-time RT-PCR (qRT-PCR) and the levels of selected serum miRNAs were analyzed further in both sexes over the full dose range. The levels of several miRNAs were significantly reduced in rats treated with 240ppm MEL&CYA versus control. In addition, miR-128-3p and miR-210-3p were decreased in males treated with 180pm MEL&CYA, a dose at which the levels of BUN and SCr were not yet affected by treatment. These data suggest that the serum miRNome is affected by nephrotoxic doses of MEL&CYA in male and female rats.

Effects of low‐dose melamine exposure during pregnancy on maternal and fetal kidneys in rats

“…More recent studies also include the neurotoxicity,, reproductive toxicity, and genotoxicity of melamine. In spite of the victims were mostly infants, adult subjects were always chosen in the experiments . Few studies in pregnant animal models have been reported …”

“…In spite of the victims were mostly infants, adult subjects were always chosen in the experiments. [17][18][19][20][21] Few studies in pregnant animal models have been reported. [22][23][24][25] Melamine-adulterated dairy products were the major sources of human contact in the milk scandal early in this millennium.…”

MicroRNAs in toxic acute kidney injury: Systematic scoping review of the current status

“…We then performed a detailed evaluation of each title and abstract and 1343 were excluded due to being other forms of AKI, miRNA studied in cells and tissues, review articles, conference abstracts or editorial/commentary, and book chapters. Finally, 35 articles were eligible for full‐text screening and we selected 21 for final analysis 12‐32 . The application of the screening process and selection criteria is summarized in Figure 1.…”

Data on the effect of heat and other technical variables on the detection of microRNAs in human serum

“…The Exiqon RT-qPCR procedure was similar to that described previously [1] . Briefly, cDNA was synthesized using a miRCURY LNA Universal cDNA Synthesis Kit II (Exiqon).…”