Neurotoxic properties of the anabolic androgenic steroids nandrolone and methandrostenolone in primary neuronal cultures.

Anabolic-androgenic steroid (AAS) abuse is associated with multiple neurobehavioral disturbances. The sites of action and the neurobiological sequels of AAS abuse are unclear at present. We investigated whether two different AASs, nandrolone and methandrostenolone, could affect neuronal survival in culture. The endogenous androgenic steroid testosterone was used for comparison. Both testosterone and nandrolone were neurotoxic at micromolar concentrations, and their effects were prevented by blockade of androgen receptors (ARs) with flutamide. Neuronal toxicity developed only over a 48-hr exposure to the steroids. The cell-impermeable analogues testosterone-BSA and nandrolone-BSA, which preferentially target membrane-associated ARs, were also neurotoxic in a time-dependent and flutamide-sensitive manner. Testosterone-BSA and nandrolone-BSA were more potent than their parent compounds, suggesting that membrane-associated ARs were the relevant sites for the neurotoxic actions of the steroids. Unlike testosterone and nandrolone, toxicity by methandrostenolone and methandrostenolone-BSA was insensitive to flutamide, but it was prevented by the glucocorticoid receptor (GR) antagonist RU-486. Methandrostenolone-BSA was more potent than the parent compound, suggesting that its toxicity relied on the preferential activation of putative membrane-associated GRs. Consistently with the evidence that membrane-associated GRs can mediate rapid effects, a brief challenge with methandrostenolone-BSA was able to promote neuronal toxicity. Activation of putative membrane steroid receptors by nontoxic (nanomolar) concentrations of either nandrolone-BSA or methandrostenolone-BSA became sufficient to increase neuronal susceptibility to the apoptotic stimulus provided by ß-amyloid (the main culprit of AD). We speculate that AAS abuse might facilitate the onset or progression of neurodegenerative diseases not usually linked to drug abuse.

[Assessment of mutagenic danger of food products]. / Otsenka stepeni mutagennoi opasnosti pishchevykh produktov.

Mutagenic effect of different food additions, hormonal stimulators of growth of agricultural animals, new foodstuffs and fodder, obtained in special conditions was studies in the experiments on mice. Mutagenic effect of plant-transformed lead also was studied. The results obtained showed the mutagenic effect of hormonal substance--metandrostenolone and nutritive stain on the basis of asostain red chlortriasin. The majority of studied food additions, new foodstuffs and fodder did not induce mutagenic effect in the used experimental conditions.

[Hepatoprotective effects of silymarin in androgenic-anabolic steroid-induced liver damage]. / Hepatoprotektivno delovanje silimarina kod ostecenja jetre izazvanog androgenim-anabolikim steroidom.

INTRODUCTION: The use and abuse of anabolic-androgenic steroids (AAS) commonly induces liver damage. MATERIAL AND METHODS: The study included 40 male Wistar rats, divided into 4 groups of 10 rats each. Animals in the first experimental group (M), were subjected to progressive systematic forced swimming test, 5 days a week, during 8 weeks. Animals in this group were treated with AAS methandienone, 2 mg/kg BW/day, per os, before swimming, 5 d/w for 8 weeks. After swimming, animals were given three times more food than the laboratory animals of the same age and kind. Animals in the second group (M+S), were subjected to progressive forced swimming test, 5 d/w 8 weeks. Animals in this group were treated with methandienone equally as the experimental group M and received the same amount of food. Apart from that, they received silymarin 20 mg/kg BW/day. Animals in the third group (K), represented the control group, which was neither subjected to swimming test, nor treated with methandienone or silymarin. Animals in this group received the same amount of food as animals in groups M and M+S. Animals in the fourth group (C), also represented a control. This group was not exercised nor treated, and animals received a standard amount of food for laboratory animals of this kind and age. Quantitative analysis of obtained hemataxylin-eosin, periodic acid shift and enzymohistochemical preparations was processed using Digital Image Analysis System: Microimage 3.0. RESULTS: It was established that processes in the nuclei of animals in groups M and K were significantly more intensive (p<0.001) in relation to groups M+S and C. The investigation of glycogen showed significantly higher density in the cells of groups M and M+S in comparison to groups K and C. Also, there was a significant difference between groups M+S and M. Density of enzyme activity of glutamate dehydrogenase in hepatocytes of animals in the group M+S was significantly higher in relation to the remaining three groups. A statistically significant difference was not found in enzyme activity of succinate dehydrogenase and lactate dehydrogenase. DISCUSSION: In cell nuclei of animals in the experimental group M, in the absence of silymarin effect, methandienone causes damages which induce regenerative processes and in this way increase high intensity activity. Silymarin significantly increases the glycogen density in hepatocytes. Increased activities of GDH are attributed to cell vitality. CONCLUSION: The present results show hepatoprotective effects of silymarin in androgenic-anabolic steroid induced liver damage.

Embryo resorption following administration of steroidal compounds to rats in mid pregnancy.

In the course of experiments on the effects of anabolic steroids on the myocardium of rat conceptuses, we found that subcutaneous implantation of 10 mg of estradiol, Dianabol or testosterone to rats in mid pregnancy, resulted in embryo resorption. Placental tissue was identified only in estradiol-treated rats which also demonstrated a large amount of serosanguineous fluid that dilated the horns considerably. The yellow nodules of placental attachment sites were represented histologically by cellular and vascular proliferations between the inner and outer layers of the myometrium. The nodular aggregates of cells had variable features according to the steroid administered. Neither decidual cells nor metrial glands that are reported to be the constituents of placental attachment sites were seen in our material. We conclude that anabolic steroids are potent agents for embryo resorption, and that the cells in the nodules of placental attachment sites are likely to be derived from the myometrium.