PWE-148 Hepatotoxicity From Anabolic Androgenic Steroids Marketed as Dietary Supplements: Contribution from Atp8B1/Abcb11 Mutations?

Abstract

):A1-A306 A191 BSG abstracts dependent-magnetic resonance imaging (BOLD-MRI) was used to quantify changes in renal oxygenation. Tissue expression and distribution of RLN receptor (RXFP1) was determined by qPCR and immunofluorescence. Expression of vasoconstrictor genes was quantified by qPCR array. Results RXFP1 was detected on glomerular podocytes, renal pericytes, and endothelial cells of the renal, segmental and interlobar arteries of cirrhotic rats. In CCl 4 cirrhosis, acute i.v. RLN (4µg) induced a 50% increase in RBF after 60 minutes (p < 0.01 vs. placebo, n = 6). BOLD-MRI showed increased tissue oxygenation at the same timepoint in renal cortex and medulla. Extended s.c. RLN increased RBF by 54% in CCl 4 (p < 0.01 vs. placebo, n = 8) and 57% in BDL (p < 0.001 vs. placebo, n = 5) and increased GFR by 138% in CCl 4 (p < 0.01 vs. placebo, n = 8) and 103% in BDL (p < 0.05 vs. placebo, n = 5). Mean arterial pressure was unaffected by RLN. L-NAME (250mg/L) orally (p.o.) abrogated the effect of RLN on RBF and GFR. The relative expression of vasoconstrictor genes in the kidney was markedly reduced by RLN treatment. Conclusion RLN increases RBF in experimental cirrhosis. Crucially, RLN also improves renal function and oxygenation but does not induce systemic hypotension even in decompensated disease. The effects of RLN are mediated via augmentation of NO and downregulation of vasoconstrictor genes known to be important in the pathogenesis of HRS. RLN has potential as a treatment for HRS and further translational studies are warranted. Disclosure of Interest None Declared.

Anabolic steroids detected in bodybuilding dietary supplements – a significant risk to public health

“…This substance emerged as a dietary supplement in the United States around 2005, marketed as 'Superdrol'; subsequently clinical case reports of serious hepatotoxicity associated with its use have been reported in the United States and the United Kingdom. [38][39][40][41][42][43][44] Although causal assessment of these cases is, in part, impeded by a lack of analytical identification of the actual substance used (either from toxicological screening of a biological sample from the patient or analysis of the product used), in our opinion it is likely that methasterone is capable of causing hepatotoxicity given the clear temporal relationship between exposure to the product and the onset of symptoms as well as pharmacological plausibility based on the accepted causal link between this structural feature and hepatotoxicity. [45,46] This could also be true of the other 17-alkylated steroids detected: DMT, methyl-1-testosterone, [2,3 d]-androisoxazol, 4-chloro-17α-methyl-andro-4-ene-3,17-diol and furazabol.…”

Liver injury from herbal and dietary supplements

“…The pattern is similar to that seen in benign recurrent intrahepatic cholestasis, caused by mutations in the ATP8B1 gene (formerly FIC1), whose dysfunction leads to impaired bilirubin and bile acid secretion, or in ATPB11 (formerly FIC2), which encodes for the bile salt canalicular transporter. Sequencing of coding exons and intron‐exon junctions of these two genes in 2 patients with anabolic steroid‐induced jaundice revealed no variants in the ATP8B1 gene and a nonsynonymous coding variant in ABCB11 of unknown significance in 1 patient …”

Human leukocyte antigen genetic risk factors of drug-induced liver toxicology

“…As exclusion is vital in the clinical management, a genotype-based test with high negative predictive value would be useful for excluding a particular drug as a cause of DILI [88]. Recently, the high negative predictive value of HLA-B*5701 genotyping was utilised in the investigation of a patient with symptomatic cholestasis with exposure to anabolic steroids as well as flucloxacillin; as the patient did not carry HLA-B*5701, anabolic steroid was identified as the agent underlying cholestasis [89].…”