RESUMEN
Misuse and abuse of anabolic androgenic steroids (AAS) such as oxymetholone (OM) cause side effects such as male infertility, cardiovascular disorders, musculoskeletal, and hepato-renal dysfunctions in athletes. The aim of this study was to evaluate the protective effects of Lepidium draba L. (L. draba) extract on OM-induced hepato-renal toxicity. Thirty adult male Wistar rats into six groups (n = 5) were randomly divided as follows: control (normal saline), OM (5 mg/kg/day), L. draba-treated (100, 200, and 400 mg/kg/d) plus 5 mg/kg/day OM, and L. draba (400 mg/kg/d) groups. Normal saline, OM and L. draba extract were orally administered for 30 days. On day 31 of the study, hepatic and renal biochemical parameters were measured. Serum cytokines (IL-1ß, IL-10, IL-6) tumor necrosis factor- α (TNF-α) and nitric oxide, levels alongside catalase, glutathione peroxidase, and superoxide dismutase activity were evaluated. Also, changes in liver and kidney histopathology were evaluated. Finally, the anti-oxidant properties of the extract were determined. The results of this study showed that in the groups treated with the L. draba extract, hepatic-renal biochemical parameters improved and also the level of nitric oxide and inflammatory cytokines decreased and the activity of anti-oxidant enzymes increased compared with the OM group. These findings revealed that L. draba, due to its high anti-oxidant properties and high content of polyphenols (especially flavonoids), can improve OM-induced hepato-renal oxidative damages. PRACTICAL APPLICATIONS: L. draba due to its remarkable anti-oxidant and anti-inflammatory properties can protects the kidney and liver injuries against oxymetholone. These features are attributed to the presence of phenolic and flavonoid components. This fidings would be helpful to desgin new therapeutic agents for treating and preventing liver/kidney injuries.
Asunto(s)
Lepidium , Oximetolona , Animales , Antioxidantes/metabolismo , Citocinas/metabolismo , Lepidium/metabolismo , Masculino , Óxido Nítrico , Estrés Oxidativo , Oximetolona/farmacología , Extractos Vegetales/farmacología , Ratas , Ratas Wistar , Solución Salina/farmacologíaRESUMEN
In the present study, we aimed to determine whether ethanol extracts of Fructus Schisandrae (FS), the dried fruit of Schizandra chinensis Baillon, mitigates the development of dexamethasone-induced muscle atrophy. Adult SPF/VAT outbred CrljOri:CD1 (ICR) mice were either treated with dexamethasone to induce muscle atrophy. Some mice were treated with various concentrations of FS or oxymetholone, a 17α-alkylated anabolic-androgenic steroid. Muscle thickness and weight, calf muscle strength, and serum creatine and creatine kinase (CK) levels were then measured. The administration of FS attenuated the decrease in calf thickness, gastrocnemius muscle thickness, muscle strength and weight, fiber diameter and serum lactate dehydrogenase levels in the gastrocnemius muscle bundles which was induced by dexamethasone in a dose-dependent manner. Treatment with FS also prevented the dexamethasone-induced increase in serum creatine and creatine kinase levels, histopathological muscle fiber microvacuolation and fibrosis, and the immunoreactivity of muscle fibers for nitrotyrosine, 4-hydroxynonenal, inducible nitric oxide synthase and myostatin. In addition, the destruction of the gastrocnemius antioxidant defense system was also inhibited by the administration of FS in a dose-dependent manner. FS downregulated the mRNA expression of atrogin-1 and muscle ring-finger protein-1 (involved in muscle protein degradation), myostatin (a potent negative regulator of muscle growth) and sirtuin 1 (a representative inhibitor of muscle regeneration), but upregulated the mRNA expression of phosphatidylinositol 3-kinase, Akt1, adenosine A1 receptor and transient receptor potential cation channel subfamily V member 4, involved in muscle growth and the activation of protein synthesis. The overall effects of treatment with 500 mg/kg FS were comparable to those observed following treatment with 50 mg/kg oxymetholone. The results from the present study support the hypothesis that FS has a favorable ameliorating effect on muscle atrophy induced by dexamethasone, by exerting anti-inflammatory and antioxidant effects on muscle fibers, which may be due to an increase in protein synthesis and a decrease in protein degradation.