Methyl Jasmonate Ameliorates Testosterone Propionate-induced Prostatic Hyperplasia in Castrated Wistar Rats.

Benign prostate hyperplasia (BPH) is a progressive disease that is related to age. Known therapeutic agents used in the treatment of BPH are associated with toxicity. Therefore, chemoprevention could be an effective approach. We investigated the ameliorative effects of methyl jasmonate (MeJA) in testosterone propionate (TP)-induced BPH in castrated rats. Castration was performed by removing both testes through the scrotum sack under ketamine anesthesia. Rats were assigned into seven groups of seven animals each: non-castrated control, castrated control, castrated rats that received TP, castrated rats that received TP and MeJA, castrated rats that received TP and finasteride, castrated rats that received MeJA, and castrated rats that received finasteride. Results indicate that BPH rats had significantly (p < 0.05) elevated prostate weight and relative weight of prostate relative to control. Also, BPH rats had significantly (p < 0.05) increased activities of prostatic acid and alkaline phosphatases, levels of zinc, and malondialdehyde. Further, levels of enzymic and non-enzymic antioxidative indices were significantly (p < 0.05) reduced in BPH. Histology of prostate revealed hyperplasia of transition lobe, increased expression of PSA, and Ki67 in BPH. Treatment with MeJA and finasteride attenuated the activities of the phosphatases and levels of antioxidants in BPH. Overall, MeJA ameliorates BPH via antioxidative mechanism. Copyright © 2017 John Wiley & Sons, Ltd.

Androgenic regulation of beta-defensins in the mouse epididymis.

BACKGROUND: The majority of beta-defensin family members are exclusively expressed in the epididymis, and some members have been shown to play essential roles in sperm maturation and fertility in rats, mice and humans. Therefore, beta-defensins are hypothesized to be potential targets for contraception and infertility diagnosis and treatment. Clarifying the regulatory mechanisms for the expression of these genes is necessary. Androgen/androgen receptor (AR) signaling plays an important regulatory role in epididymal structure and function. However, very little is known about the androgenic regulation on the production and secretion of the epididymal beta-defensins. METHODS: The expression of beta-defensins was detected by quantitative RT-PCR. The androgen dependence of beta-defensins was determined by bilateral orchiectomy and androgen supplementation. The androgen response elements (AREs) in the promoters of beta-defensins were identified using the MatInspector software. The binding of AR to AREs was assayed by ChIP-PCR/qPCR. RESULTS: We demonstrated that 23 mouse caput epididymal beta-defensins were differentially regulated by androgen/androgen receptor. Six genes, Defb18, 19, 20, 39, 41, and 42, showed full regulation by androgens. Ten genes, Defb15, 30, 34, 37, 40, 45, 51, 52, 22 and Spag11a, were partially regulated by androgens. Defb15, 18, 19, 20, 30, 34, 37, 39, 41, 42, 22 and Spag11a were associated with androgen receptor binding sites in their promoter or intronic regions, indicating direct regulation of AR. Six genes, Defb1, 12, 13, 29, 35, and spag11b/c, exhibited an androgen-independent expression pattern. One gene, Defb25, was highly dependent on testicular factors rather on androgens. CONCLUSIONS: The present study provides novel insights into the mechanisms of androgen regulation on epididymal beta-defensins, enabling a better understanding of the function of beta-defensins in sperm maturation and fertility.

Physicochemical properties of inclusion complexes of highly soluble ß-cyclodextrins with highly hydrophobic testosterone propionate.

Hydroxypropyl-ß-cyclodextrin (HP-ß-CyD) and sulfobutyl ether-ß-cyclodextrin (SBE-ß-CyD) were used to generate hydrophilic complexes of the poorly water-soluble drug testosterone propionate (TP). The inclusion complexes were obtained by freeze-drying, and then analyzed at both liquid and solid states. Phase solubility studies, performed according to the type-AL solubility diagrams of TP in presence of both CyDs, suggested the formation of water-soluble complexes at 1:1 molar ratio. These results were confirmed by continuous variation method (Job's plot). Both CyDs increased water-solubility of TP 100-fold as compared to the native drug. The host-guest arrangement of CyD complexes in a water solution was further investigated by one- and two-dimensional NMR spectroscopy, highlighting the insertion of the tetracyclic ring of TP into the CyD cavity, and the interaction of the pending ester chain of drug with the primary hydroxyl groups of CyDs at the narrow end of the toroid structure. In solid phase, FTIR-ATR spectroscopy showed that the CO stretching mode of the TP vibrational spectrum changed if the complex between the drug and CyDs occurred. This change is temperature-dependent, and its evolution, accounted for by deconvolution procedures, provided the thermodynamic parameters explaining the mechanisms involved in the formation of inclusion complexes.

Steroids' transformations in Penicillium notatum culture.

The application of Penicillium notatum genus for biotransformations of steroids has been investigated. The reactions observed include insertion of an oxygen atom into D-ring of steroids, 15alpha-hydroxylation of 17alpha-methyl testosterone derivatives, ester bond hydrolysis, and degradation of a testosterone derivatives side chain. Microbial production of testolactones, the biologically active compounds, was also achieved using this strain in up to 98% yield.

Atomistic description of the solubilisation of testosterone propionate in a sodium dodecyl sulfate micelle.

Large-scale molecular dynamics simulations were used to study the structural and dynamic properties of the solubilization process of testosterone propionate (TSTP) within sodium dodecyl sulfate (SDS) micelles. We observed that the TSTP spontaneously adsorb onto the SDS micelles and preferentially reside among the polar head groups of the SDS molecules. We found that the SDS micelle is slightly aspherical in size and has a surface area of ∼170 Å(2)/molecule, while the SDS+TSTP micelle is more aspherical and has a surface area of ∼156 Å(2)/molecule. The structural properties of the interior of the SDS micelle and the hydration of the SDS headgroup are largely undisturbed by the presence of the TSTP. However, there seems to be a correlation between the location of the TSTP molecules and the location of Na(+) counterions on the surface of the SDS micelle. Additionally, we also observe that the TSTP molecules diffuse on the surface of the SDS micelle and try to organize themselves such that they are approximately equidistant from one another.

Drug solubilisation in lipid nanoparticles containing high melting point triglycerides.

The effect of lipid (either the triglyceride trilaurin or tripalmitin, melting points of 43 and 64 °C, respectively) on the properties of lipid nanoparticles (LN) stabilised by the surfactant, polyoxyethylene-10-oleyl ether (C18:1E10) at a temperature of 22 °C, has been determined. LN were prepared by heating lipid, surfactant and water to 70 °C and cooling to ambient temperature with constant stirring. While lipid type influenced LN formation in that trilaurin-containing LN formed over the greatest range of compositions, phase inversion studies suggested that both lipids formed a core within the LN while light scattering studies indicated that the size of both types of LN varied with lipid concentration: in an approximately linear fashion for clear or opalescent LN and exponentially for cloudy LN. Additionally, both types of preformed LN exhibited an increase in solubilisation capacity of the hydrophobic drug, testosterone propionate compared to C18:1E10 micelles, although the trilaurin-containing LN exhibited the greatest increase. Differential scanning calorimetry studies demonstrated that trilaurin formed a 'fluid-like' core and therefore liquefied-lipid nanoparticles, which allowed dissolution of testosterone propionate in the lipid core. In contrast, tripalmitin was present in a 'solid-like' state forming solid lipid nanoparticles which did not allow testosterone propionate dissolution in the core.

Enhanced transdermal bioavailability of testosterone propionate via surfactant-modified ethosomes.

The current investigation aimed to evaluate the transdermal potential of novel testosterone propionate (TP) ethosomes and liposomes prepared by surfactant modification. The effect of hexadecyl trimethyl ammonium bromide and cremophor EL-35 on the particle size and zeta potential of the prepared vesicles was investigated. The entrapment efficiency and stability, as well as in vitro and in vivo skin permeation, were studied with the various techniques, such as differential scanning calorimetry, confocal laser scanning microscopy, transmission electron microscopy, dynamic light scattering, and so on. The results indicated that the ethosomes were defined as spherical, unilamellar structures with low polydispersity (0.100 ± 0.015) and nanometric size (156.5 ± 3.5 nm). The entrapment efficiency of TP in ethosomal and liposomal carriers was 92.7% ± 3.7% and 64.7% ± 2.1%, respectively. The stability profile of the prepared TP ethosomal system assessed for 120 days revealed very low aggregation and very low growth in vesicular size. TP ethosomes also provided an enhanced transdermal flux of 37.85 ± 2.8 µg/cm(2)/hour and a decreased lag time of 0.18 hours across mouse skin. The skin permeation efficiency of the TP ethosomes as further assessed by confocal laser scanning microscopy revealed enhanced permeation of rhodamine red-loaded formulations to the deeper layers of the skin (260 µm) than that of the liposomal formation (120 µm).