DOCSLIB.ORG

Direct and Indirect Effects of Guggulsterone on the Induction of Beiging in Mature 3T3-L1 Adipocytes

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Direct and Indirect Effects of Guggulsterone on the Induction of Beiging in Mature 3T3-L1 Adipocytes Direct and Indirect effects of Guggulsterone on the Induction of Beiging in Mature 3T3-L1A Adipocytes B 1 1 5 t Control GS 6 µM GS 25 µM 1 2 2 2 2 n 2 e Colette N. Miller, Yusra Azhar, Ashish Parmar, Janaiya Samuels, Rangaiaht 1 1 0 Shashidharamurthy,* Srujana Rayalam n PGC1a ) l A o c o r 1 2 l t 1 0 5 Department of Foods and Nutrition, University of Georgia, Athens, GA Department of Pharmaceutical Sciences, School of a Pharmacy, Philadelphia College of Osteopathic Medicine- GA Campus, Suwanee, GA i Cn o n tro l IS O G S 6 u M G S 2 5 u M PPARy r o d c n 1 0 0 o % ( h U C P 1 c B-Actin o t 9 5 i Abstract Direct Effects of GS on 3T3-L1 AdipocytesM GS signaling 9 0 T B X 1 Phytochemicals have long demonstrated anti-obesity properties in C o n tro l G S 2 5 u M Phytochemicals may induce beiging through nuclear receptor activation. adipocytes. Their ability, however, to induce browning in white adipose GS induces mitochondrial biogenesisC D T u b lin tissue is only beginning to emerge. We have recently established that the white adipocyte cell line, 3T3-L1, is capable of beiging under beta- 5 0 0 2 0 0 Control Iso 10mM p = 0 .1 8 adrenergic conditions. Using this information, we sought to investigate if the B p = 0 .1 8 A 4 0 0 1 5 0 ) plant steroid guggulsterone (GS) can induce beiging in 3T3-L1s. 3T3-L1 ) l l o o r preadipocytes were differentiated using established protocols r C o n tro l IS O G S 6 u M G S 2 5 u M t t 3 0 0 1 R n supplemented with rosiglitazone and thyroid hormone. Direct effects of GS n C A o o 1 0 0 P c c G were measured by treating mature 3T3-L1s for 24 hours. Indirect effects 2 0 0 P U C P 1 P % % ( ( were measured by treating mature 3T3-L1s with conditioned media from GS 6.25μM GS 25μM 5 0 GS-treated RAW 264.7 macrophages. Direct treatment of 3T3-L1s with GS 1 0 0 resulted in increased lipolysis, increased mitochondrial activity (11%), and T B X 1 increased peroxisome proliferator-activated receptor gamma coactivator 1- 0 0 C o n tro l G S 6 u M G S 2 5 u M C o n tro l G S 6 u M G S 2 5 u M alpha (PGC1α) levels by 250% more than control. 3T3-L1s also T u b liAn demonstrated an increase in uncoupling protein 1 (UCP1) expression by GS induces adipocyte beiging 200% and beige marker, T-box protein 1 (TBX1) expression by 80% more B C than control. Furthermore, this was accompanied by increased levels of G 4 0 0 GS treatment appears to protein-coupled bile acid receptor (TGR5) and its downstream target * A upregulate TGR5-DIO2 pathway iodothyronine deiodinase 2 (DIO2). Treatment of RAW 264.7 macrophages * C o n tro l IS O G S 6 u M G S 2 5 u M in 3T3-L1s. 3 0 0 ) ) with GS induced a 60% increase in catecholamine release into the media ) l l l o o o r r compared to control. Using this conditioned media from macrophages, 3T3- U C P 1 r 1 1 1 t t t P P P n n L1 adipocytes increased the expression of DIO2 and UCP1 following 24 n 2 0 0 o o o C C C c c c U U U hours of incubation. Results from this study demonstrate that GS can T B X 1 % % % ( ( potentially induce beiging in white adipose tissue through two distinct ( 1 0 0 mechanisms: (1) direct signaling through the TGR5-cAMP-DIO2 pathway T u b lin B and (2) indirectly through stimulating catecholamine release in Working Model macrophages. Thus, it is reasonable to conclude that GS may improve the B 0 A C o n tro l IS O G S 6 u M G S 2 5 u M metabolic capacity of adipose tissue thereby counteracting the effects of C 1 2 0 1 0 0 obesity. * * * ) ) y y l 3 0l 0 t t * * * * i i 8 0 o o l l i i r r t t * b b n n a a i i 6 0 o o v v c c l l l l e e % % 4 0 ( ( C C ) ) ) l l l 2 0 0 * o o o 2 0 r r r 1 1 Indirect Effects1 of GS on 3T3-L1 Adipocytes t t Research Goals t n n n X X X 0 o o o B B B l o M M M M M c c c r u u u u u T T • Determine if the anti-obesity phytochemical, guggulsterone, can T t n 1 3 6 .5 5 o 2 2 C S S S G G G 1 S % % A GS protects against% 1 0 0 LPS-injury in RAWG 264.7 macrophages S ( ( promote mitochondrial biogenesis and beiging in 3T3-L1 adipocytes. ( G C C • Investigate if guggulsterone1 2 0 mediates mitochondrial biogenesis through direct or indirect signaling. B 1 0 0 102 0 * * * * * * * ) y 1 0 0 C o n tro l IS O G S 6 u M G S 2 5 u M# l t i 8 0 o l ) ) y y i l l r t t i i t 8 0 o o l l b i i r r n t t a b b i * * * * n n * * * * a 6 0 a o i i v 6 0 o o v v c c c l l l l l l e e e % % 4 0 % ( ( C Direct4 0 Effects of GS on C ( C 2 0 2 0 0 l 3T3-L1 Adipocytes o L M M M M r 0 t /m u u u u n g 1 6 1 6 o u S S S S C o n tro l G S 6 u M G S 1 2 .5 u M G S 2 5 u M C 1 G G G G Conclusions S + + P L S S P P L L B GS appears to have 2 distinct effects on adipocyte beiging: GS decreases adipogenesis C GS induces catecholamine secretion in RAW 264.7 macrophages that can upregulate 1) Direct signaling in adipocytes leading to upregulation of thermogenic/ 2 0 0 5 0 0 n 1 2 0 n UCP1 in adipocytes beiging makers and enhanced mitochondrial biogenesis. This effect o o i i e e t t 4 0 0 * * * * c c s s appears to be partly mediated through TGR5 signaling. u * * * * u ) ) a a l 1 0 0 l d d o o e e o o r r t l l r r 3 0 0 t 1 5 0 t 2) Indirect signaling in adipocytes through macrophage M2 ) p p ) ) e e n n n l l l r r o o e e e 8 0 # o t o o c c d d i i r e e 2 0 0 polarization and catecholamine secretion. r r t n x x t t % % n n o o ( ( o n i i * * * * n n c c c 6 0 o i 1 0 0 i o o 1 0 0 r r m m * * * * t t c * * * i i d c c a a i l l N N p % o 4 0 o i 0 ( % % h h ( ( L l o L M M M c c r * * * * 5 0 t /m u u u e e n g 6 5 5 o 2 2 t 2 0 t u C S 1 G S S a a S G G Financial Support P + C C *p<0.05 L S 0 P 0 L **p<0.01 C o n tro l G S 6 u M G S 1 2 .5 u M G S 2 5 u M ***p<0.001 Funding was provided by the Philadelphia College of Osteopathic Medicine C o n tro l IL 4 G S 6 u M ****p<0.0001 Biomedical Research Program. #p<0.05 vs. + control.
Load more

Recommended publications
  • St John's Institute of Dermatology
    St John’s Institute of Dermatology Topical steroids This leaflet explains more about topical steroids and how they are used to treat a variety of skin conditions. If you have any questions or concerns, please speak to a doctor or nurse caring for you. What are topical corticosteroids and how do they work? Topical corticosteroids are steroids that are applied onto the skin and are used to treat a variety of skin conditions. The type of steroid found in these medicines is similar to those produced naturally in the body and they work by reducing inflammation within the skin, making it less red and itchy. What are the different strengths of topical corticosteroids? Topical steroids come in a number of different strengths. It is therefore very important that you follow the advice of your doctor or specialist nurse and apply the correct strength of steroid to a given area of the body. The strengths of the most commonly prescribed topical steroids in the UK are listed in the table below. Table 1 - strengths of commonly prescribed topical steroids Strength Chemical name Common trade names Mild Hydrocortisone 0.5%, 1.0%, 2.5% Hydrocortisone Dioderm®, Efcortelan®, Mildison® Moderate Betamethasone valerate 0.025% Betnovate-RD® Clobetasone butyrate 0.05% Eumovate®, Clobavate® Fluocinolone acetonide 0.001% Synalar 1 in 4 dilution® Fluocortolone 0.25% Ultralanum Plain® Fludroxycortide 0.0125% Haelan® Tape Strong Betamethasone valerate 0.1% Betnovate® Diflucortolone valerate 0.1% Nerisone® Fluocinolone acetonide 0.025% Synalar® Fluticasone propionate 0.05% Cutivate® Hydrocortisone butyrate 0.1% Locoid® Mometasone furoate 0.1% Elocon® Very strong Clobetasol propionate 0.1% Dermovate®, Clarelux® Diflucortolone valerate 0.3% Nerisone Forte® 1 of 5 In adults, stronger steroids are generally used on the body and mild or moderate steroids are used on the face and skin folds (armpits, breast folds, groin and genitals).
    [Show full text]
  • Small Molecules in Solution Has Rarely Been Reported, However, As a General Guide We Recommend Storage in DMSO at -20°C
    (Z)-Guggulsterone Small Molecules Retinoic acid receptor (RAR) pathway inhibitor; Inhibits farnesoid X receptor (FXR) Catalog # 73702 1 mg Product Description (Z)-Guggulsterone is a plant steroid found in the resin of the guggul plant Commiphora mukul that acts as a selective antagonist of farnesoid X receptor (FXR; Cui et al.). It decreases chenodeoxycholic acid (CDCA)-induced FXR activation (IC ₅₀ = 10 µM) in the presence of 100 µM CDCA (Urizar et al.; Cui et al.). Molecular Name: (Z)-Guggulsterone Alternative Names: Not applicable CAS Number: 39025-23-5 Chemical Formula: C₂₁H₂₈O₂ Molecular Weight: 312.5 g/mol Purity: ≥ 95% Chemical Name: (8R,9S,10R,13S,14S,17Z)-17-ethylidene-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15- decahydrocyclopenta[a]phenanthrene-3,16-dione Structure: Properties Physical Appearance: A crystalline solid Storage: Product stable at -20°C as supplied. Protect product from prolonged exposure to light. For long-term storage store with a desiccant. For product expiry date, please contact [email protected]. Solubility: · DMSO ≤ 800 µM · Absolute ethanol ≤ 3.2 µM · DMF ≤ 30 mM For example, to prepare a 10 mM stock solution in DMF, resuspend 1 mg in 320 μL of DMF. Prepare stock solution fresh before use. Information regarding stability of small molecules in solution has rarely been reported, however, as a general guide we recommend storage in DMSO at -20°C. Aliquot into working volumes to avoid repeated freeze-thaw cycles. The effect of storage of stock solution on compound performance should be tested for each application. Compound has low solubility in aqueous media.
    [Show full text]
  • Steroids and Other Appearance and Performance Enhancing Drugs (Apeds) Research Report
    Research Report Revised Febrero 2018 Steroids and Other Appearance and Performance Enhancing Drugs (APEDs) Research Report Table of Contents Steroids and Other Appearance and Performance Enhancing Drugs (APEDs) Research Report Introduction What are the different types of APEDs? What is the history of anabolic steroid use? Who uses anabolic steroids? Why are anabolic steroids misused? How are anabolic steroids used? What are the side effects of anabolic steroid misuse? How does anabolic steroid misuse affect behavior? What are the risks of anabolic steroid use in teens? How do anabolic steroids work in the brain? Are anabolic steroids addictive? How are anabolic steroids tested in athletes? What can be done to prevent steroid misuse? What treatments are effective for anabolic steroid misuse? Where can I get further information about steroids? References Page 1 Steroids and Other Appearance and Performance Enhancing Drugs (APEDs) Research Report Esta publicación está disponible para su uso y puede ser reproducida, en su totalidad, sin pedir autorización al NIDA. Se agradece la citación de la fuente, de la siguiente manera: Fuente: Instituto Nacional sobre el Abuso de Drogas; Institutos Nacionales de la Salud; Departamento de Salud y Servicios Humanos de los Estados Unidos. Introduction Appearance and performance enhancing drugs (APEDs) are most often used by males to improve appearance by building muscle mass or to enhance athletic performance. Although they may directly and indirectly have effects on a user’s mood, they do not produce a euphoric high, which makes APEDs distinct from other drugs such as cocaine, heroin, and marijuana. However, users may develop a substance use disorder, defined as continued use despite adverse consequences.
    [Show full text]
  • Spironolactone 2021 Newborn Use Only
    Spironolactone 2021 Newborn use only Alert Spironolactone is a potassium-sparing diuretic and concomitant intake of potassium or ACE inhibitors may lead to hyperkalemia. Indication Diuretic primarily prescribed for its potassium-sparing effect. For heart failure, in conjunction with furosemide. For chronic lung disease, in conjunction with a thiazide diuretic. Bartter syndrome and Gitelman Syndrome. Action Spironolactone is a synthetic steroid that acts as a competitive aldosterone receptor antagonist, so inhibits sodium reabsorption and spares potassium. It is a weak diuretic. It also inhibits the interaction between dihydrotestosterone and the intracellular androgen receptor resulting in moderate antiandrogenic activity. Drug type Non-selective mineralocorticoid receptor antagonist. Trade name Aldactone; Spiractin Presentation Oral suspension prepared in pharmacy: 1 mg/mL; 2.5 mg/mL; 5 mg/mL. Dose 1–3 mg/kg/dose 24 hourly. Dose can be divided into different intervals. Dose adjustment Therapeutic hypothermia – Not applicable. Renal impairment – Refer to precautions section. Hepatic impairment – Refer to precautions section. Maximum dose 3 mg/kg/day Total cumulative dose Route Oral Preparation Oral suspension. Administration Administer undiluted with feeds. Monitoring Serum potassium at regular intervals. Contraindications Hyperkalaemia. Significant renal impairment. Anuria. Adrenal insufficiency. Precautions Use with caution in infants with renal or hepatic impairment. Monitor more frequently if infant is also given potassium. Drug interactions Spironolactone increases the effects of ACE inhibitors (leading to hyperkalemia), digoxin and sotalol. Adverse reactions Hyperkalaemia and metabolic acidosis. Antiandrogenic effects include reduced hirsutism and gynecomastia. There is one case report of an ovarian cyst in a neonate on spironolactone. Spironolactone interferes with 17-hydroxyprogesterone measurement, which is used to screen neonates for congenital adrenal hyperplasia.
    [Show full text]
  • Inhaled and Oral Corticosteroids
    Inhaled and Oral Corticosteroids Corticosteroids (steroids) are medicines that are used to treat many chronic diseases. Corticosteroids are very good at reducing inflammation (swelling) and mucus production in the airways of the lungs. They also help other quick-relief medicines work better. The steroids (corticosteroids) used to treat asthma and other chronic lung diseases are not the same as anabolic steroids, used illegally by some athletes for bodybuilding. Corticosteroids do not affect the liver or cause sterility. Does the Body Make Steroids? Corticosteroids are similar to cortisol, a hormone produced by the adrenal glands in the body. Cortisol is one of the body's own natural steroids. Cortisol is essential for life and well being. During stress, our bodies produce extra cortisol to keep us from becoming very sick. Normally the adrenal glands release cortisol into the blood stream every morning. The brain monitors this amount and regulates the adrenal function. It cannot tell the difference between its own natural cortisone and that of steroid medicines. Therefore, when a person takes high doses of steroids over a long time, the brain may decrease or stop cortisol production. This is called adrenal supression. Health care providers generally decrease a steroid dosage slowly to allow the adrenal gland to recover and produce cortisol at a normal level again. If you have been on steroids long- term do not stop taking them suddenly. Follow your doctor’s prescription. What are Some Steroid Medicines? Steroid medicines are available as nasal sprays, metered- dose-inhalers (inhaled steroids), oral forms (pills or syrups), injections into the muscle (shots) and intravenous (IV) solutions.
    [Show full text]
  • Pharmacologic Characteristics of Corticosteroids 대한신경집중치료학회
    REVIEW J Neurocrit Care 2017;10(2):53-59 https://doi.org/10.18700/jnc.170035 eISSN 2508-1349 Pharmacologic Characteristics of Corticosteroids 대한신경집중치료학회 Sophie Samuel, PharmD1, Thuy Nguyen, PharmD1, H. Alex Choi, MD2 1Department of Pharmacy, Memorial Hermann Texas Medical Center, Houston, TX; 2Department of Neurosurgery and Neurology, The University of Texas Medical School at Houston, Houston, TX, USA Corticosteroids (CSs) are used frequently in the neurocritical care unit mainly for their anti- Received December 7, 2017 inflammatory and immunosuppressive effects. Despite their broad use, limited evidence Revised December 7, 2017 exists for their efficacy in diseases confronted in the neurocritical care setting. There are Accepted December 17, 2017 considerable safety concerns associated with administering these drugs and should be limited Corresponding Author: to specific conditions in which their benefits outweigh the risks. The application of CSs in H. Alex Choi, MD neurologic diseases, range from traumatic head and spinal cord injuries to central nervous Department of Pharmacy, Memorial system infections. Based on animal studies, it is speculated that the benefit of CSs therapy Hermann Texas Medical Center, 6411 in brain and spinal cord, include neuroprotection from free radicals, specifically when given Fannin Street, Houston, TX 77030, at a higher supraphysiologic doses. Regardless of these advantages and promising results in USA animal studies, clinical trials have failed to show a significant benefit of CSs administration Tel: +1-713-500-6128 on neurologic outcomes or mortality in patients with head and acute spinal injuries. This Fax: +1-713-500-0665 article reviews various chemical structures between natural and synthetic steroids, discuss its E-mail: [email protected] pharmacokinetic and pharmacodynamic profiles, and describe their use in clinical practice.
    [Show full text]
  • TIBOLONE 2.5MG TAB Class: Estrogen and Progestin
    TIBOLONE 2.5MG TAB Class: Estrogen and Progestin Combination(synthetic steroid hormone) Indications: Prevention of postmenopausal osteoporosis; symptomatic treatment of hot flushes and associated sweating resulting from menopause (surgical or natural); improvement of bone mineral density in patients with established postmenopausal osteoporosis Available dosage form in the hospital: TIBOLONE 2.5MG TAB Dosage: -Symptoms associated with menopause: Females: Oral: 2.5 mg once daily. Initiate ≥1 year after naturally occurring menopause, or immediately in women with surgical menopause or those being treated with gonadotropin releasing hormone (GnRH) analogues. Note: Use caution in women >60 years of age due to increased stroke risk -Switching from other hormone replacement therapy (HRT): If on sequential HRT, initiate tibolone 1 day after the completion of the current treatment cycle. If on continuous-combined HRT, may initiate tibolone therapy immediately. Note: A separate progestogen should not be added to tibolone. -Missed dose: If >12 hours has elapsed, skip dose and resume at next regularly scheduled time. -Osteoporosis prophylaxis in postmenopausal women (unlabeled use in some countries): Oral: 2.5 mg once daily (Bundred, 2012; Roux, 2002). Note: In women >60 years of age, an increased risk of stroke was reported when taking 1.25 mg daily (Cummings, 2008). Geriatric Refer to adult dosing. Use caution in women >60 years of age due to increased stroke risk. Renal Impairment: No dosage adjustment provided in manufacturer’s labeling; use with caution (may increase risk of fluid retention). Hepatic Impairment: Use is contraindicated in acute or chronic liver disease. Common side effect: Common side effects observed in clinical studies (occurring in 1-10% of the women using Livial) were: vaginal bleeding or spotting abdominal pain weight gain breast pain unnatural hair growth vaginal symptoms, such as discharge, itching, and Pregnancy Risk Factor: D (Adverse events have been observed in animal reproduction studies; use is contraindicated during pregnancy).
    [Show full text]
  • Nandrolone Decanoate Inhibits Gluconeogenesis and Decreases Fasting Glucose in Wistar Male Rats
    S P FRANKENFELD and others Nandrolone decanoate and 220:2 143–153 Research glucose metabolism Nandrolone decanoate inhibits gluconeogenesis and decreases fasting glucose in Wistar male rats Stephan Pinheiro Frankenfeld1, Leonardo Pires de Oliveira3, Daniele Lea˜o Ignacio3, Raquel Guimara˜es Coelho2, Mariana Nigro Mattos4, Andrea Claudia Freitas Ferreira2, Denise Pires Carvalho2 and Rodrigo Soares Fortunato1 1Laboratory of Molecular Radiobiology, Institute of Biophysics Carlos Chagas Filho, UFRJ, CCS, 2Laboratory of Correspondence Endocrine Physiology, Institute of Biophysics Carlos Chagas Filho, 3Laboratory of Exercise Biology, should be addressed School of Physical Education and Sports and 4Laboratory of Bioenergetics, Institute of Medical Biochemistry, to R S Fortunato Federal University of Rio de Janeiro, Avenida Carlos Chagas Filho, 373, Block G - Underground - Room G0-031, Email 21941-902 Rio de Janeiro, RJ, Brazil [email protected] Abstract The use of anabolic–androgenic steroids to improve physical performance or appearance has Key Words increased notably. The doses used are 10- to 100- fold higher than the therapeutic dose (TD), " glucose and this abuse can cause several side effects. Glucose metabolism is significantly affected by " anabolic–androgenic steroids anabolic–androgenic steroid abuse, but studies about glycemic regulation during fasting are " gluconeogenesis scarce. There are some evidences showing that testosterone can antagonize glucocorticoids " insulin action, which are crucial to glucose production during fasting. Thus, the aim of this study was to determine the impact of supraphysiological doses (SDs) of nandrolone decanoate Journal of Endocrinology (DECA) on rat glucose metabolism during fasting. Male Wistar rats were treated with i.m. injections of vehicle, a low TD (0.016 mg/100 g b.w.-TD group) or a high SD (1 mg/100 g b.w.-SD group) of DECA, once a week for 8 weeks.
    [Show full text]
  • Transformations of Steroid Esters by Fusarium Culmorum Alina S´ Wizdor*, Teresa Kołek, and Anna Szpineter
    Transformations of Steroid Esters by Fusarium culmorum Alina S´ wizdor*, Teresa Kołek, and Anna Szpineter Department of Chemistry, Agricultural University, Norwida 25, 50-375 Wrocław, Poland. Fax: 0048-071-3283576. E-mail: [email protected] * Author for correspondence and reprint requests Z. Naturforsch. 61c, 809Ð814 (2006); received April 6/May 15, 2006 The course of transformations of the pharmacological steroids: testosterone propionate, 4-chlorotestosterone acetate, 17-estradiol diacetate and their parent alcohols in Fusarium culmorum AM282 culture was compared. The results show that this microorganism is capable of regioselective hydrolysis of ester bonds. Only 4-ene-3-oxo steroid esters were hydrolyzed at C-17. 17-Estradiol diacetate underwent regioselective hydrolysis at C-3 and as a result, estrone Ð the main metabolite of estradiol Ð was absent in the reaction mixture. The alcohols resulting from the hydrolysis underwent oxidation at C-17 and hydroxylation. The same products (6- and 15α-hydroxy derivatives) as from testosterone were formed by transformation of testosterone propionate, but the quantitative composition of the mixtures obtained after transformations of both substrates showed differences. The 15α-hydroxy deriv- atives were obtained from the ester in considerably higher yield than from the parent alcohol. The presence of the chlorine atom at C-4 markedly reduced 17-saponification in 4-chloro- testosterone acetate. Only 3,15α-dihydroxy-4α-chloro-5α-androstan-17-one (the main prod- uct of transformation of 4-chlorotestosterone) was identified in the reaction mixture. 6- Hydroxy-4-chloroandrostenedione, which was formed from 4-chlorotestosterone, was not de- tected in the extract obtained after conversion of its ester.
    [Show full text]
  • Spironolactone 2016
    Spironolactone 2016 Alert Spironolactone is a potassium-sparing diuretic and concomitant intake of potassium or ACE inhibitors may lead to hyperkalemia. Indication Diuretic primarily prescribed for its potassium-sparing effect. For heart failure, in conjunction with furosemide. For chronic lung disease, in conjunction with a thiazide diuretic. Bartter syndrome and Gitelman Syndrome. Action Spironolactone is a synthetic steroid that acts as a competitive aldosterone receptor antagonist, so inhibits sodium reabsorption and spares potassium. It is a weak diuretic. It also inhibits the interaction between dihydrotestosterone and the intracellular androgen receptor resulting in moderate antiandrogenic activity.. Drug Type N on - selective mineralocorticoid receptor antagonist. Trade Name Aldactone; Spiractin Presentation Oral suspension prepared in pharmacy. 2.5 mg/mL; 5 mg/mL. Dosage / Interval 1 – 3 mg/kg/dose 24 hourly. Dose can be divided into different intervals. Maximum daily dose 3 mg/kg/day Route Oral Preparation/Dilution Oral suspension. Administration Administer undiluted with feeds. Monitoring Serum potassium at regular intervals. Contraindications Hyperkalaemia . Significant renal impairment. Anuria. Adrenal insufficiency. Precautions Use with caution in infants with renal or hepatic impairment. Monitor more frequently if infant is also given potassium. Drug Interactions Spironolactone increases the effects of ACE inhibitors (leading to hyperkalemia), digoxin and sotalol. Adverse Reactions Hyperkalaemia and metabolic acidosis. Antiandrogenic effects include reduced hirsutism and gynecomastia. There is one case report of an ovarian cyst in a neonate on spironolactone. Spironolactone interferes with 17-hydroxyprogesterone measurement, which is used to screen neonates for congenital adrenal hyperplasia. Reduces clearance of digoxin. Compatibility N/A Incompatibility N/A Stability Biochemical stability when stored in solution for 1 month.1 Storage Store below 25oC.
    [Show full text]
  • Effect of Nandrolone Decanoate (Anabolic
    b Meta olis g m & ru D T o f x o i Journal of Drug Metabolism and l c a o n l o Mwaheb et al., J Drug Metab Toxicol 2017, 8:1 r g u y o J Toxicology DOI: 10.4172/2157-7609.1000224 ISSN: 2157-7609 Research Article Open Access Effect of Nandrolone Decanoate (Anabolic Steroid) on the Liver and Kidney of Male Albino Rats and the Role of Antioxidant (Antox-Silymarin) as Adjuvant Therapy Amal RS Mohammed1, Ghada M Al-Galad1, Amro A Abd-Elgayd1, Marwa A Mwaheb1* and Hala M Elhanbuli2 Department of Forensic Medicine and Clinical Toxicology, Fayoum University, Egypt 2Department of Pathology, Fayoum University, Egypt *Corresponding author: Marwa A Mwaheb, Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Fayoum University, Egypt, Tel: 0201006267354; E-mail: [email protected] Received date: January 3, 2017; Accepted date: January 25, 2017; Published date: February 1, 2017 Copyright: © 2017 Mwaheb MA, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Background and objective: The present study is determining the effect of Nandrolone Decanoate (ND) administration on the liver and kidney of white male albino rats. In addition, study the possible protective effect of administration of Antox and Silymarin on ND. Methods: The sample consisted of 110 male albino rats that divided into eleven groups treated by Nandrolone Decanoate at a dose of 7.93 mg/kg and 11.9 mg/kg then treated by Silymarin or Antox or both for 8 weeks.
    [Show full text]
  • Hepatotoxicity Associated with Illicit Use of Anabolic Androgenic Steroids in Doping
    Eur opean Rev iew for Med ical and Pharmacol ogical Sci ences 2017; 21 (1 Suppl): 7-16 Hepatotoxicity associated with illicit use of anabolic androgenic steroids in doping R. SOLIMINI, M.C. ROTOLO, L. MASTROBATTISTA, C. MORTALI, A. MINUTILLO, S. PICHINI, R. PACIFICI, I. PALMI Department of Therapeutic Research and Medicines Evaluation, Drug Abuse and Doping Unit, Istituto Superiore di Sanità, Rome, Italy Abstract. – Anabolic Androgenic Steroids Since then , several synthetic analogs of testos - (AAS) abuse and misuse is nowadays a harmful terone, known as Anabolic Androgenic Steroids habit involving both professional or recreational (AAS) or designer steroids (e.g . methyltestos - athletes, as well as general population. AAS are also frequently present in over-the-counter di - terone in 1935 , nandrolone in 1950 and 1953, etary supplements without being declared in the testosterone esters from mid-1950s, stanozolol list of ingredients, leaving consumers unaware and oxymetholone in 1959 , oxandrolone in 1962) of the risks of adverse effects. Indeed, health have been produced in the attempt to minimize risks of AAS consumption in pharmaceutical the androgenic effects and improve the anabolic preparations or dietary complements seem still ones 1,2,7-9 . However , a successful complete sepa - underestimated and under-reported. The variety of complications due to AAS misuse involves ration of the anabolic and the androgenic proper - cardiovascular, central nervous, musculoskeletal ties has never been realized in the synthetic de - and genitourinary systems of both males and fe - rivatives of testosterone 1,2,10,11 . Among those, nan - males; psychiatric and behavioral effects, dam - drolone was the first compound which showed a ages to metabolic system, skin and mainly liver.
    [Show full text]