Liver Injury after Selective Androgen Receptor Modulator Intake: A Case Report and Review of the Literature.

Liver injury associated with selective androgen receptor modulators (SARMs) is an issue that has not been reported often. We report a case of a previously healthy 24-year-old male, who was referred to our hospital for severe jaundice with intense pruritus. He had previously taken the SARM Enobosarm (also known as Ostarine) for muscle-building purposes. Blood serum levels of total bilirubin exceeded 30 mg/dL with only a slight elevation of liver enzymes. Liver biopsy revealed isolated hepatocellular cholestasis (bland cholestasis) with limited inflammation or necrosis. Supportive treatment was begun in our hospital with molecular adsorbent recirculation system (MARS) albumin dialysis, as well as cholestyramine for pruritus relief. During therapy, bilirubin levels and symptoms regressed, and after five sessions of dialysis, the patient could be released from our clinic in a markedly improved clinical and laboratory condition. However, bilirubin parameters regressed slowly after this, reaching normal levels as late as six months after first intake of the compound. Exome-based genetic testing brought about no pathogenic variants for cholestatic liver disease in our patient. Nevertheless, three common heterozygous polymorphisms associated with an increased risk for intrahepatic cholestasis could be identified. Our case demonstrates that SARMs can cause severe liver injuries not prominently mentioned in safety data sheets. Therefore, these compounds constitute a potential danger to the user's health. This holds especially true when taking SARMs without supervision by a medical professional, which should consist of a thorough monitoring of liver enzyme and bilirubin levels.

A Dietary Supplement Containing Fucoidan Preserves Endothelial Glycocalyx through ERK/MAPK Signaling and Protects against Damage Induced by CKD Serum.

(1) Damage to the endothelial glycocalyx (eGC), a protective layer lining the endothelial luminal surface, is associated with chronic kidney disease (CKD), which leads to a worsening of cardiovascular outcomes in these patients. Currently, there are no targeted therapeutic approaches. Whether the dietary supplement EndocalyxTM (ECX) protects against endothelial damage caused by uremic toxins is unknown. (2) We addressed this question by performing atomic force microscopy measurements on living endothelial cells. We examined the effect of ECX on eGC thickness at baseline and with pooled serum from hemodialysis patients. ECX was also successfully administered in vivo in mice, in which eGC was assessed using perfused boundary region measurements by intravital microscopy of cremasteric vessels. (3) Both ECX and fucoidan significantly improved baseline eGC thickness. Our data indicate that these effects are dependent on ERK/MAPK and PI3K signaling. After incubation with eGC damaging serum from dialysis patients, ECX increased eGC height. Intravital microscopy in mice revealed a relevant increase in baseline eGC dimensions after feeding with ECX. (4) We identified a dietary supplement containing glycocalyx substrates and fucoidan as potential mediators of eGC preservation in vitro and in vivo. Our findings suggest that fucoidan may be an essential component responsible for protecting the eGC in acute settings. Moreover, ECX might contribute to both protection and rebuilding of the eGC in the context of CKD.