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      RAD-140 Drug-Induced Liver Injury

      case-report

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          Abstract

          Background: RAD-140, one of the novel selective androgen receptor modulators (SARMs), has potent anabolic effects on bones and muscles with little androgenic effect. Despite the lack of approval for its clinical use, RAD-140 is readily accessible on the consumer market. Hepatotoxicity associated with the use of SARMs has only rarely been reported in the literature.

          Case Report: A 24-year-old male presented with a 2-week history of diffuse abdominal pain, scleral icterus, pruritus, and jaundice. Prior to presentation, he had been taking the health supplement RAD-140 for muscle growth for 5 weeks. He had a cholestatic pattern of liver injury, with a peak total bilirubin of 38.5 mg/dL. Liver biopsy was supportive of a diagnosis of RAD-140–associated liver injury characterized pathologically by intracytoplasmic and canalicular cholestasis with minimal portal inflammation. Symptoms and liver injury resolved after cessation of the offending agent.

          Conclusion: To date, only select descriptions of the potential hepatoxicity associated with the use of SARMs, including RAD-140, have been published. Given their potential hepatoxicity and ready availability on the consumer market, RAD-140 and other SARMs should be used judiciously and under close clinical supervision until further hepatic safety data become available.

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          Most cited references16

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          Hepatobiliary transporters and drug-induced cholestasis.

          Drug-induced liver injury is an important clinical problem with significant morbidity and mortality. Whereas for most hepatocellular forms of drug-induced hepatic injury the underlying pathophysiological mechanism is poorly understood, there is increasing evidence that cholestatic forms of drug-induced liver damage result from a drug- or metabolite-mediated inhibition of hepatobiliary transporter systems. In addition to their key role in determining hepatic drug exposure and clearance, the coordinated action of these transport systems is essential for bile formation and the biliary secretion of cholephilic compounds and xenobiotics. Any drug-mediated functional disturbance of these processes can lead to an intracellular accumulation of potentially harmful bile constituents and result in the development of cholestatic liver cell damage. In addition to direct drug-mediated inhibition of hepatocellular transport, function of these transporters can be altered by pre-existing hepatic disease and genetic factors, which contribute to the development of drug-induced cholestasis in susceptible individuals. This review summarizes current knowledge about the function of hepatobiliary uptake and efflux systems and discusses factors that might predispose to drug-induced cholestasis.
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            Selective Androgen Receptor Modulators: Current Knowledge and Clinical Applications

            Selective androgen receptor modulators (SARMs) differentially bind to androgen receptors depending on each SARM's chemical structure. As a result, SARMs result in anabolic cellular activity while avoiding many of the side effects of currently available anabolic steroids. SARMs have been studied in the treatment of breast cancer and cachexia and have also been used as performance-enhancing agents. Here, we evaluate and summarize the current literature on SARMs.
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              Chemical Composition and Labeling of Substances Marketed as Selective Androgen Receptor Modulators and Sold via the Internet

              Question What types and quantity of ingredients are found in products sold through the internet and advertised to contain selective androgen receptor modulators? Findings Chemical analyses of 44 products sold via the internet as selective androgen receptor modulators revealed that only 52% contained selective androgen receptor modulators and another 39% contained another unapproved drug. In addition, 25% of products contained substances not listed on the label, 9% did not contain an active substance, and 59% contained substance amounts that differed from the label. Meaning Selective androgen receptor modulators, which have not been approved by the US Food and Drug Administration, were available through the internet and were inaccurately labeled. Importance Recent reports have described the increasing use of nonsteroidal selective androgen receptor modulators, which have not been approved by the US Food and Drug Administration (FDA), to enhance appearance and performance. The composition and purity of such products is not known. Objective To determine the chemical identity and the amounts of ingredients in dietary supplements and products marketed and sold through the internet as selective androgen receptor modulators and compare the analyzed contents with product labels. Design and Setting Web-based searches were performed from February 18, 2016, to March 25, 2016, using the Google search engine on the Chrome and Internet Explorer web browsers to identify suppliers selling selective androgen receptor modulators. The products were purchased and the identities of the compounds and their amounts were determined from April to August 2016 using chain-of-custody and World Anti-Doping Association–approved analytical procedures. Analytical findings were compared against the label information. Exposures Products marketed and sold as selective androgen receptor modulators. Main Outcomes and Measures Chemical identities and the amount of ingredients in each product marketed and sold as selective androgen receptor modulators. Results Among 44 products marketed and sold as selective androgen receptor modulators, only 23 (52%) contained 1 or more selective androgen receptor modulators (Ostarine, LGD-4033, or Andarine). An additional 17 products (39%) contained another unapproved drug, including the growth hormone secretagogue ibutamoren, the peroxisome proliferator-activated receptor-δ agonist GW501516, and the Rev-ErbA agonist SR9009. Of the 44 tested products, no active compound was detected in 4 (9%) and substances not listed on the label were contained in 11 (25%). In only 18 of the 44 products (41%), the amount of active compound in the product matched that listed on the label. The amount of the compounds listed on the label differed substantially from that found by analysis in 26 of 44 products (59%). Conclusions and Relevance In this limited investigation involving chemical analyses of 44 products marketed as selective androgen receptor modulators and sold via the internet, most products contained unapproved drugs and substances. Only 52% contained selective androgen receptor modulators and many were inaccurately labeled. This study conducted web-based searches for products marketed as selective androgen receptor modulators, which are performance-enhancing drugs that have not been approved by the US Food and Drug Administration, and compared the chemical identities and the amount of ingredients in each product with those listed on the product label.
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                Author and article information

                Journal
                Ochsner J
                Ochsner J
                TOJ
                ochjnl
                The Ochsner Journal
                Academic Division of Ochsner Clinic Foundation
                1524-5012
                1524-5012
                Winter 2022
                Winter 2022
                : 22
                : 4
                : 361-365
                Affiliations
                [ 1 ]Department of Gastroenterology and Hepatology, VA Loma Linda Healthcare System , Loma Linda, CA
                [ 2 ]University of California , Riverside, Riverside, CA
                [ 3 ]Loma Linda University , Loma Linda, CA
                Author notes
                Address correspondence to Muhammad B. Hammami, MD, Department of Gastroenterology and Hepatology, VA Loma Linda Healthcare System, 26001 Redlands Blvd., Redlands, CA 92373. Tel: (909) 825-7084, ext. 2419. Email: bader.hammami@ 123456medsch.ucr.edu
                Article
                toj.22.0005
                10.31486/toj.22.0005
                9753945
                36561105
                56622c19-e5ae-4c02-83aa-ce33bcee8297
                ©2022 by the author(s); Creative Commons Attribution License (CC BY)

                © 2022 by the author(s); licensee Ochsner Journal, Ochsner Clinic Foundation, New Orleans, LA. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( creativecommons.org/licenses/by/4.0/legalcode) that permits unrestricted use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

                History
                Page count
                Figures: 1, Tables: 2, References: 18, Pages: 5
                Categories
                Case Reports and Clinical Observations

                chemical and drug induced liver injury,enobosarm,lgd-4033,rad140

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