Abstract
miRNAs are a family of 20–22 non-coding nucleotides that control gene expression by inhibiting the translation of their target messenger RNAs (mRNAs). Two models have been proposed to elucidate the mechanism of action: they act either hindering mRNA translation or enhancing mRNA degradation. Anabolic-Androgenic Steroids (AASs) represent a class of drugs used to treat several diseases. In the last few years, AASs have frequently been used for aesthetic purposes, indeed, they form part of the larger group called image- and performance-enhancing drugs (IPEDs). Long-term AAS use can lead to serious health consequences. In this regard, the present study aimed to analyze the role of several microRNAs (miRNAs) in renal damage after AAS use, to better understand the underlying mechanisms. For this purpose, two miRNAs (miR-21 and miR-205) were tested in two groups: AAS group (seven males, mean age 33.28 ± 4.68 years; mean body mass index (BMI) 27.04 ± 1.07), and chronic kidney disease (CKD) group (seven males, mean age 66.2 ± 5.4 years; mean BMI 24.75 ± 1.35). Finally, the same miRNAs were tested in the “Control” group (seven males, mean age 44.85 ± 5.75 years; mean BMI 26.5 ± 1.88). Kolmogorov-Smirnov Test was used to determine the normality of data distribution. All variables were normally distributed. Student’s t-test was used for comparisons between two groups. Analyzing the results of the present study, the two tested miRNAs (miR-21 and miR-205) were significantly higher in the CKD group compared to the AAS group, with mir-21 being much more expressed than miR-205. This study represents a pilot study to define if these expression patterns could be studied in other biological samples (plasma, urine) in subjects with different kidney injury linked to chronic kidney diseases and AAS use, to identify reliable biomarkers that could be applied in clinical and forensic diagnostics, as well as a target for toxicological investigations or therapeutic treatments.
Highlights
MiRNAs are a family of 20–22 non-coding nucleotides that control gene expression by inhibiting the translation of their target messenger RNAs (O’Brien et al, 2018)
The present study demonstrates that the different investigated situations, Anabolic-Androgenic Steroids (AASs) use and chronic kidney disease (CKD), caused miRNA dysregulation at the kidney level
The main limitation of this study is related to the fact that the AASs use was ascertained through a toxicological examination, even if data about the exact duration of use is unknown. Another significant limitation is related to the small number of subjects enrolled in the AAS group. Concerning this last consideration, it is important to highlight that the number of subjects who die with a positive toxicological test for anabolic-androgenic steroids is low in Italy: for example, in our Institute, we found only 7 cases analyzing 1,700 autopsy records from the last 15 years
Summary
MiRNAs are a family of 20–22 non-coding nucleotides that control gene expression by inhibiting the translation of their target messenger RNAs (mRNAs) (O’Brien et al, 2018). Two models have been proposed to elucidate the mechanism of action: they act either hindering mRNA translation or enhancing mRNA degradation (Catalanotto et al, 2016) In consideration of their fundamental functions, in the last few decades, they have been investigated as the main goal of a large number of scientific studies with the following aims: on the one hand to identify the underlying altered pathway, focusing on the modification of their expression in cases of pathology (Sessa et al, 2019); on the other hand, in cases of a specific disease, to ascertain if miRNAs could be involved, becoming both diagnostic markers and, possibly, therapeutic targets (Sessa et al, 2018b; Sessa et al, 2020). AAS epidemiology and prevalence are higher in Europe, the Middle East, North America (the USA), Oceania (Australia and New Zealand), and
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