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RAD140 is neuroprotective against apoptotic insults. Cultures were treated with 50 M zVAD-fmk (A), 10 nM T (B), 100 nM RAD140 (C), or 100 nM RAD192 (D) for 1 hour, followed by exposure to 50 M A1-42, 3 M AAII, or 25 M H 2 O 2 for 24 hours, and processed for cell viability. Data show mean ( SEM) cell viability expressed as percentage of vehicle-treated control (Veh, open bar). *, P .001 relative to the corresponding vehicle-treated condition (gray bars); n 3.
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The decline in testosterone levels in men during normal aging increases risks of dysfunction and disease in androgen-responsive tissues, including brain. The use of testosterone therapy has the potential to increase the risks for developing prostate cancer and or accelerating its progression. To overcome this limitation, novel compounds termed sele...
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Context 1
... previously showed that androgen neuroprotection is limited to insults that involve apoptosis (48). To inves- tigate whether the SARMs mimic this established andro- gen-protective pathway, we assessed their abilities to re- duce cell death induced by 3 insults: A, apoptosis activator II (AAII), and hydrogen peroxide (H 2 O 2 ). To confirm our prior observations that A and AAII, but not H 2 O 2 , induce cell death by caspase-dependent ap- optosis in our culture system, we evaluated the ability of the caspase inhibitor zVAD to attenuate cell death. Exposure of cultures to 50 M zVAD-fmk for 2 hours prior to insult exposure significantly attenu- ated cell death due to 50 M A and 3 M AAII but did not significantly affect cell loss caused by 25 M H 2 O 2 ( Figure 2A). Next, we com- pared the pattern of protection against the 3 insults by T and the 2 SARMs. Cultures were pretreated for 1 hour with 10 nM testosterone, 100 nM RAD140, or 100 nM RAD192, and then exposed for 24 hours to A, AAII, or H 2 O 2 . T (Fig- ure 2B), RAD140 ( Figure 2C), and RAD192 ( Figure 2D) shared similar protective profiles of significantly ...
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... previously showed that androgen neuroprotection is limited to insults that involve apoptosis (48). To inves- tigate whether the SARMs mimic this established andro- gen-protective pathway, we assessed their abilities to re- duce cell death induced by 3 insults: A, apoptosis activator II (AAII), and hydrogen peroxide (H 2 O 2 ). To confirm our prior observations that A and AAII, but not H 2 O 2 , induce cell death by caspase-dependent ap- optosis in our culture system, we evaluated the ability of the caspase inhibitor zVAD to attenuate cell death. Exposure of cultures to 50 M zVAD-fmk for 2 hours prior to insult exposure significantly attenu- ated cell death due to 50 M A and 3 M AAII but did not significantly affect cell loss caused by 25 M H 2 O 2 ( Figure 2A). Next, we com- pared the pattern of protection against the 3 insults by T and the 2 SARMs. Cultures were pretreated for 1 hour with 10 nM testosterone, 100 nM RAD140, or 100 nM RAD192, and then exposed for 24 hours to A, AAII, or H 2 O 2 . T (Fig- ure 2B), RAD140 ( Figure 2C), and RAD192 ( Figure 2D) shared similar protective profiles of significantly ...
Context 3
... previously showed that androgen neuroprotection is limited to insults that involve apoptosis (48). To inves- tigate whether the SARMs mimic this established andro- gen-protective pathway, we assessed their abilities to re- duce cell death induced by 3 insults: A, apoptosis activator II (AAII), and hydrogen peroxide (H 2 O 2 ). To confirm our prior observations that A and AAII, but not H 2 O 2 , induce cell death by caspase-dependent ap- optosis in our culture system, we evaluated the ability of the caspase inhibitor zVAD to attenuate cell death. Exposure of cultures to 50 M zVAD-fmk for 2 hours prior to insult exposure significantly attenu- ated cell death due to 50 M A and 3 M AAII but did not significantly affect cell loss caused by 25 M H 2 O 2 ( Figure 2A). Next, we com- pared the pattern of protection against the 3 insults by T and the 2 SARMs. Cultures were pretreated for 1 hour with 10 nM testosterone, 100 nM RAD140, or 100 nM RAD192, and then exposed for 24 hours to A, AAII, or H 2 O 2 . T (Fig- ure 2B), RAD140 ( Figure 2C), and RAD192 ( Figure 2D) shared similar protective profiles of significantly ...
Context 4
... previously showed that androgen neuroprotection is limited to insults that involve apoptosis (48). To inves- tigate whether the SARMs mimic this established andro- gen-protective pathway, we assessed their abilities to re- duce cell death induced by 3 insults: A, apoptosis activator II (AAII), and hydrogen peroxide (H 2 O 2 ). To confirm our prior observations that A and AAII, but not H 2 O 2 , induce cell death by caspase-dependent ap- optosis in our culture system, we evaluated the ability of the caspase inhibitor zVAD to attenuate cell death. Exposure of cultures to 50 M zVAD-fmk for 2 hours prior to insult exposure significantly attenu- ated cell death due to 50 M A and 3 M AAII but did not significantly affect cell loss caused by 25 M H 2 O 2 ( Figure 2A). Next, we com- pared the pattern of protection against the 3 insults by T and the 2 SARMs. Cultures were pretreated for 1 hour with 10 nM testosterone, 100 nM RAD140, or 100 nM RAD192, and then exposed for 24 hours to A, AAII, or H 2 O 2 . T (Fig- ure 2B), RAD140 ( Figure 2C), and RAD192 ( Figure 2D) shared similar protective profiles of significantly ...
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Citations
... RAD-140 suppressed cancer growth in models of metastatic breast cancer, which express androgen and estrogen receptors, and had an acceptable safety profile [77]. RAD-140 has also been reported to have neuroprotective effects by reducing programmed cell death of neurons in various neurodegenerative rat models [78]. ...
Background and objectives. Selective androgen receptor modulators (SARMs) are androgen receptor ligands that exhibit pronounced anabolic effects but demonstrate tissue selectivity regarding their androgenic effects. Despite the established beneficial effects of non-steroidal SARMs in several socially significant diseases, they also exhibit side effects. The purpose of this study was to present the currently reported adverse effects of SARMs in animals and humans. Clinical trials have been conducted with the non-steroidal group of modulators; however, in some cases, they were not sufficiently effective, and in others, the results have not yet been reported. To date, no non-steroidal SARM has been approved as a drug, but these substances are freely available on the Internet. Their frequency of use is increasing, which poses significant health risks. Materials and methods. To conduct this review, we identified and screened articles on SARMs using the Google Scholar, ScienceDirect, and PubMed electronic databases. Results. An increasing number of cases of liver damage due to the misuse of SARMs were reported during the period 2020–2024. In both humans and animals, non-steroidal SARMs frequently cause adverse changes in lipid profile indicators, as well as in gonadotropic and sex hormone concentrations. Cases of myocarditis, rhabdomyolysis, gynecomastia, and tendon rupture have been documented in amateur users of SARMs. Conclusion. In conclusion, SARMs are not safe, and measures must be taken to control and regulate their online trade. Additionally, greater efforts are needed to publicize information related to their side effects.
... 21 The administration of SARM RAD140 did not cause an increase in the size of the seminal vesicles and the prostate. 22 This study has some limitations. The intricate biological effects of steroid hormones and SARMs vary depending on the binding affinity and degree of agonism and antagonism to ARs in various types of tissues. ...
BACKGROUND Selective androgen receptor modulators (SARMs) have been investigated as a potential treatment for hypogonadism, a condition characterized by low testosterone levels in men. The idea is to provide therapeutic benefits similar to traditional testosterone replacement therapy. However, research in this area is still in its early stages, and more extensive studies are needed to establish the efficacy of SARM. This study aimed to determine the impact of SARM RAD140 on testosterone levels, fibromuscular stroma, and prostate mass in rats undergoing bilateral orchidectomy. METHODS This was an in vivo study using posttest-only control group design in rats (Rattus norvegicus). The positive and negative control groups consisted of rats with and without bilateral orchidectomy, respectively. The treatment groups were rats given SARM RAD140 with and without orchidectomy. Testosterone levels, histopathology, and prostate mass were examined at the end of week 6, and the quantitative data were analyzed using one-way ANOVA. RESULTS This study found no difference in prostate mass (0.598 [0.05] g versus 0.590 [0.07] g, p = 0.984), fibromuscular stroma ratio (0.483 [0.094] versus 0.463 [0.057], p = 0.984), and testosterone level (0.006 [0.005] ng/dl versus 0.014 [0.004] ng/dl, p = 0.098) compared to positive control with orchidectomy and SARM RAD140 administration 6 weeks after treatment. CONCLUSIONS There were no differences in testosterone levels, prostate mass, or the ratio of fibromuscular stroma to epithelium area in rats undergoing bilateral orchidectomy and placebo surgery with the administration of SARM RAD140.
... [63][64] It has been evaluated for treatment of hormone receptor-positive breast cancer and neurodegenerative disease. 65,66 Currently, the drug has not achieved FDA approval for use and remains in phase I of clinical trials. Despite lack of approval or clear safety data, RAD-140 remains among the most widely used SARMs for athletic performance. ...
Selective androgen receptor modulators (SARMs) are a class of nonsteroidal drugs that are favored over anabolic androgenic steroids (AASs) for their tissue-selectivity and improved side-effect profile. These drugs have been evaluated for treatment of various diseases including muscle-wasting disorders, osteoporosis, and breast cancer. Despite lacking approval for therapeutic use, SARMs are widely used recreationally as performance enhancing drugs by bodybuilders and athletes. In recent years, cases of drug-induced liver injury (DILI) secondary to SARMs have begun to emerge, but little is known regarding their hepatotoxicity. In this review, we provide current knowledge regarding DILI from SARMs. A literature search was conducted regarding SARMs and liver injury to evaluate relevant cases and information. SARMs have been associated with a cholestatic syndrome congruent with that of DILI from AASs, and it consists of a bland cholestasis in which there is minimal bile duct injury, inflammation, or necrosis. Patients present with an insidious onset of jaundice with marked hyperbilirubinemia and mild hepatic enzyme elevations. No clear treatment exists, although patients typically show improvement with cessation of the offending SARM. Given the novelty of these drugs, further study is necessary to understand diagnosis, management, and complications of SARM-related DILI.
... 13,29,59 Several SARMs have been developed that serve as site-specific androgen receptor agonists at other locations such as the nervous system. 36 It is possible that other SARM formulations could also alleviate muscle pain; however, our results cannot be generalized to these other compounds. Next, we only tested the analgesic effects of SARMs in a mouse model of widespread muscle pain. ...
Chronic pain is a significant health problem associated with disability and reduced quality of life. Current management of chronic pain is inadequate with only modest effects of pharmacological interventions. Thus, there is a need for the generation of analgesics for treating chronic pain. While preclinical and clinical studies demonstrate the analgesic effects of testosterone, clinical use of testosterone is limited by adverse androgenic effects. Selective androgen receptor modulators (SARMs) activate androgen receptors and overcome treatment limitations by minimizing androgenic side effects. Thus, we tested if daily soluble SARMs or a SARM-loaded microparticle formulation alleviated muscle hyperalgesia in a mouse-model of widespread pain (male and female C57BL/6J mice). We tested if the analgesic effects of the SARM-loaded microparticle formulation was mediated through androgen receptors by blocking androgen receptors with flutamide pellets. In vitro and in vivo release kinetics were determined for SARM-loaded microparticles. Safety and toxicity of SARM treatment was determined using serum cardiac and liver toxicity panels, heart histology, and conditioned place preference testing. Subcutaneous daily SARM administration, and 2 injections, I week apart, of SARM-loaded microparticles alleviated muscle hyperalgesia in both sexes and was prevented with flutamide treatment. Sustained release of SARM, from the microparticle formulation, was observed both in vitro and in vivo for 4 weeks. SARM treatment produced no cardiac or liver toxicity and did not produce rewarding behaviors. These studies demonstrate SARM-loaded microparticles alleviate muscle pain, release drug for a sustained period, are safe, and may serve as a potential therapeutic for chronic muscle pain.
... The SARM we utilized was designed to target bone and skeletal muscle tissue (8,48,49). Several SARMs have been developed that serve as site specific androgen receptor agonists at other locations such as the nervous system (70). It is possible that other SARM formulations could also alleviate muscle pain, however our results cannot be generalized to these other compounds. ...
Currently, there is a need for the generation of non-opioid analgesics for treating chronic pain. Preclinical and clinical studies demonstrate the analgesic effects of testosterone. However, treatment with testosterone is not feasible due to adverse effects. Selective androgen receptor modulators (SARMs) were developed to overcome these limitations by minimizing activation of androgenic side effects. First, we demonstrate SARM administration alleviates widespread muscle pain in male and female mice. We then developed a SARM-loaded PLGA microparticle formulation that reverses widespread muscle pain in two injections. In vitro and in vivo release kinetics demonstrate the microparticle formulation had sustained SARM release for 4 weeks. Antagonism of androgen receptors blocked the analgesic effects of the SARM microparticles. SARM treatment had no effect on cardiac or liver enzymes, cardiac histology, and did not produce rewarding behavior. These studies demonstrate SARM microparticles as a potential therapeutic for chronic muscle pain.
One Sentence Summary
A selective androgen receptor modulator microparticle formulation alleviates widespread muscle pain in male and female mice while being non-toxic.
... Помимо Т, в качестве нейрорегенерационной терапии могут использоваться другие андрогены (оксандролон, станозолол, нандролон и т.д.), а также селективные модуляторы андрогенных рецепторов, которые оказывают нейропротекторное действие при БА [103], но требуют проведения дополнительных исследований. ...
Alzheimer's disease (AD) is a neurodegenerative disease that causes dementia in half of the cases. Asthma is usually found in people over 65 years of age. The etiopathogenesis of the disease is multifactorial and includes genetic factors, nutritional disorders, mitochondrial dysfunction, oxidative stress, and aging. Sex hormones have an important influence on the development of AD, as evidenced by a higher incidence in women than in men. Considering the significant influence of T on the maintenance of normal brain function, the present study is aimed at evaluating the impact of androgen deprivation therapy (ADT), as well as testosterone therapy, on the risk of AD development and progression. Although there is some clinical inconsistency between studies, androgens have a significant effect on brain function and are beneficial for AD patients. Low levels of circulating androgens should be considered as a significant risk factor for the development of AD and memory loss. With a reduced level of T in the plasma of men, its administration improves cognitive performance and memory, treatment should be started at an early stage of the disease. In men and women with AD, androgens improve mental state and slow the progression of the disease, providing a protective effect. In the future, it is necessary to conduct studies on a large population, taking into account personality factors and a more specific approach to assessing cognitive functions and the causal relationship of T administration in AD.
... Preclinical studies have indicated anabolic properties of several SARMs (15), as well as some neuroprotective (16) or anticancer (14) (21), although an enobosarm trial suggested some improvement in glucose control and IR (17). ...
... Besides T, other androgens can be used as neuroregeneration therapy in men and women, such as synthetic androgens (oxandrolone, stanozolol, nandrolone, etc.) and the selective androgen receptors modulators (SARM), which have a relevant neuroprotective effect in AD [113] and this potential therapeutic applications are still being explored. ...
Alzheimer’s disease (AD) is a neurodegenerative disease responsible for almost half of all dementia cases in the world and
progressively increasing. The etiopathology includes heritability, genetic factors, aging, nutrition, but sex hormones play a
relevant role. Animal models demonstrated that testosterone (T) exerted a neuroprotective effect reducing the production of
amyloid-beta (Aβ), improving synaptic signaling, and counteracting neuronal death. This study aims to evaluate the impact of
T deprivation and T administration in humans on the onset of dementia and AD. A search was conducted on MEDLINE and
Scopus for the “androgen deprivation therapy” and “testosterone therapy” with “dementia” and “Alzheimer’s.” Studies lasting
twenty years with low risk of bias, randomized clinical trial, and case-controlled studies were considered. Twelve articles on
the effect of androgen deprivation therapy (ADT) and AD and seventeen on T therapy and AD were retrieved. Men with prostate
cancer under ADT showed a higher incidence of dementia and AD. The effect of T administration in hypogonadal men
with AD and cognitive impairment has evidenced some positive results. The majority of studies showed the T administration
improved memory and cognition in AD while others did not find any benefit. Although some biases in the studies are evident,
T therapy for AD patients may represent an essential clinical therapy to reduce dementia incidence and AD progression.
However, more specific case-controlled trials on the effect of androgens therapy in men and women to reducing the onset of
AD are necessary.
... For example, RAD140 also known as testolone delayed the programmed nerve cell death in various neurodegenerative models in rats. The mechanisms of this neuroprotective effect were related to MAPK (mitogen-activated protein kinase) -signal pathways (Jayaraman et al. 2014). It can be speculated that this effect of RAD140 could be used in the treatment of Alzheimer's and other neurodegenerative diseases. ...
The current issue is the third of the eighth volume of the Athens Journal of Sports, published by the Sport, Exercise, & Kinesiology Unit of the ATINER under the aegis of the Panhellenic Association of Sports Economists and Managers (PASEM).
... For example, RAD140 also known as testolone delayed the programmed nerve cell death in various neurodegenerative models in rats. The mechanisms of this neuroprotective effect were related to MAPK (mitogen-activated protein kinase) -signal pathways (Jayaraman et al. 2014). It can be speculated that this effect of RAD140 could be used in the treatment of Alzheimer"s and other neurodegenerative diseases. ...
Selective androgen receptor modulators (SARMs) are an exciting group of molecules with pronounced anabolic effects and very weak to missing androgenic ones. This is due to the tissue selectivity they possess and is their big advantage over anabolic androgenic steroids (AAS). As a result of this SARMs tend to be a big promise for improving the treatment process in different socially significant diseases such as osteoporosis, muscle wasting, benign prostatic hyperplasia, hypogonadism, sexual dysfunction, neurodegenerative diseases etc. SARMs are included in the prohibited list of World Anti-Doping agency (WADA) as they are a temptation for a lot of athletes regarding the exerted strong anabolic effect. However, as SARMs are freely available on the internet there are some reports for positive doping tests in professional sports connected with them. Still further research is needed to examine all the side effects of SARMs. Some of them may be harmful so both professional and amateur sportsmen, their coaches and doctors should be informed about this interesting topic. Keywords: SARM(s), anabolic effect, sports, doping, side effects
