Selective androgen receptor modulator use and related adverse events including drug-induced liver injury: Analysis of suspected cases.

PURPOSE: Selective androgen receptor modulators (SARMs) have demonstrated agonist activity on the androgen receptor in various tissues, stimulating muscle mass growth and improving bone reconstruction. Despite being in clinical trials, none has been approved by the Food and Drug Administration (FDA) or European Medicines Agency for pharmacotherapy. Still, SARMs are very popular as performance-enhancing drugs. The FDA has issued warnings about the health risks associated with SARMs, but the long-term exposure and possible adverse events still need to be fully understood. This review aims to evaluate the adverse events associated with using SARMs by humans. METHODS: PubMed database was searched from September 16, 2022, to October 2, 2023. In total, 20 records were included in the final review. Data from preclinical and clinical studies supported the review. RESULTS: Since 2020, 20 reports of adverse events, most described as drug-induced liver injury associated with the use of SARM agonists, have been published. The main symptoms mentioned were cholestatic or hepatocellular liver injury and jaundice. Limited data are related to the dosages and purity of SARM supplements. CONCLUSION: Promoting SARMs as an anabolic agent in combination with other performance-enhancing drugs poses a risk to users not only due to doping controls but also to health safety. The lack of quality control of consumed supplements makes it very difficult to assess the direct impact of SARMs on the liver and their potential hepatotoxic effects. Therefore, more detailed analyses are needed to determine the safety of using SARMs.

Macrophage Activity under Hyperglycemia: A Study of the Effect of Resveratrol and 3H-1,2-Dithiole-3-thione on Potential Polarization.

Currently, research is focused on bioactive compounds with the potential to promote macrophage polarization with the aim of reducing the development of inflammatory-related diseases. However, the effect of bioactive compounds under oxidative-stress-induced hyperglycemia on macrophage polarization has been scarcely investigated. RAW 264.7 macrophages were incubated under standard (SG) or high glucose (HG) conditions and stimulated with lipopolysaccharide (LPS) (10, 60 and 100 ng/mL) to monitor macrophage polarization after resveratrol (RSV) or 3H-1,2-dithiole-3-thione (D3T) supplementation (2.5, 5, 10 and 20 µM). Under SG and HG conditions without LPS stimulation, RSV significantly decreased macrophage viability at the highest concentration (20 µM), whereas D3T had no or low effect. LPS stimulation at 60 and 100 ng/mL, under SG and HG conditions, increased significantly macrophage viability. Both RSV and D3T significantly decreased NO production in LPS-stimulated macrophages under HG condition, whereas only D3T increased GSH levels at 100 ng/mL and normalized MDA values at 60 ng/mL of LPS under HG condition. Under 60 ng/mL LPS stimulation and HG, mRNA IL-1 and IL-6 were higher. Interestingly, RSV decreased pro-inflammatory interleukins; meanwhile, D3T increased Arg1 and IL-10 relative expression. Overall, our results indicate that hyperglycemia plays a fundamental role in the modulation of macrophage-induced inflammation in response to bioactive compounds.

Bioactive Compounds and Adipocyte Browning Phenomenon.

Overweight and obesity have become worldwide health issues in most countries. Current strategies aimed to prevent or reduce overweight and obesity have mainly focused on the genes and molecular mechanisms that give the functional characteristics to different types of adipose tissue. The Browning phenomenon in adipocytes consists of phenotypic and metabolic changes within white adipose tissue (WAT) activated by thermogenic mechanisms similar to that occurring in brown adipose tissue (BAT); this phenomenon has assumed great relevance due to its therapeutic potential against overweight and obesity. In addition, the study of inflammation in the development of overweight and obesity has also been included as a relevant factor, such as the pro-inflammatory mechanisms promoted by M1-type macrophages in adipose tissue. Studies carried out in this area are mainly performed by using the 3T3-L1 pre-adipocyte cell line, testing different bioactive compound sources such as plants and foods; nevertheless, it is necessary to standardize protocols used in vitro as well to properly scale them to animal models and clinical tests in order to have a better understanding of the mechanisms involved in overweight and obesity.