Melatonin attenuates glucocorticoid effect induced by medroxyprogesterone acetate in rats.

Medroxyprogesterone acetate (MPA) acts on glucocorticoid receptors and, when it is in excess, can cause clinical disorders comparable to hyperadrenocorticism. Melatonin (MEL) is a hormone with potent antioxidant and anti-glucocorticoid activity and it can be beneficial in the excessive activation of glucocorticoid receptors. To evaluate the protective effects of MEL on the glucocorticoid effect of MPA, 34 male Wistar rats were randomized into four groups: CON (control), MEL, MPA, and MPA + MEL. The animals were treated for 28 days, by subcutaneous injection. At the high dose that we used, the MPA caused effects compatible with an excessive activation of glucocorticoid receptors, resulting on a reduction in adrenal size, less weight gain, lower final body weight and feeding efficiency, and fewer lymphocytes compared with the control group. In addition, there was an increase in abdominal fat, cholesterol, very-low-density lipoprotein (VLDL), triglycerides, erythrocytes, hemoglobin, hematocrit, and hepatic vacuolization. We concluded that MEL was effective reducing the mean values of total cholesterol, high-density lipoprotein (HDL), urea, VLDL, triglycerides, hepatic microvacuolization and abdominal fat/weight in rats treated with MPA. These findings indicate that MEL attenuates the harmful effects of MPA.

Topical formulations containing Copaifera duckei Dwyer oleoresin improve cutaneous wound healing.

OBJECTIVE: Evaluation of the healing and toxicological effects of Copaifera duckei Dwyer oleoresin (CDO). MATERIALS AND METHODS: Rodents with skin lesions were divided into nine groups, including daily treatments with 1, 3 and 10% CDO, collagenase, antibiotic ointment and control groups, for 14 days. RESULTS: Treatment with 10% CDO reduced skin edema and hyperplasia, demonstrating anti-inflammatory effect of the oil. Reduction in the wound area was observed, indicating the healing effect of CDO. Histopathological analysis showed increases in angiogenesis and re-epithelialization in animals treated with the highest concentration. On the other hand, no alterations in ulcerations, inflammatory infiltrate, hemorrhage, congestion, degeneration, percentage of collagen fibers, number of cells stained with anti-macrophage migration inhibitory factor, or density of area stained with anti-collagen I and III were found. Toxicogenetic analysis revealed no differences in micronucleus frequencies or in the ratio of polychromatic erythrocytes to total erythrocytes between treated and negative control, demonstrating the absence of genotoxicity and cytotoxicity, respectively. There was no difference in levels of liver enzymes among groups, indicating the absence of hepatotoxicity. CONCLUSION: Formulations of CDO exerted beneficial effects on the stages of cutaneous wound healing and are promising options for the treatment of wounds.

Melatonin loaded lecithin-chitosan nanoparticles improved the wound healing in diabetic rats.

Wound healing in diabetic patients remains a worldwide problem that can cause amputations and even lead to death. This work aimed to produce lecithin-chitosan nanoparticles loaded with melatonin (MEL-NP) incorporated in a topical formulation to be evaluated for healing in the in vivo animal model for diabetes. To produce nanoparticles, an ethanolic solution containing soybean lecithin and melatonin was added dropwise to an aqueous solution of chitosan under sonication. The nanoparticles were physicochemical characterized and evaluated in vivo for toxicity using the Galleria mellonella model and its potential for wound healing in diabetic rats. The MEL-NPs presented a particle size of 160 nm and a zeta potential of 25 mV. The melatonin entrapment efficiency was 27%. Our results indicated that treatment with MEL-NP improved wound healing demonstrated by wound closure earlier than the other treatments evaluated. A desired therapeutic effect was achieved by MEL-NP in the induction of fibroblast and angiogenic proliferation. In addition, it was accompanied by an expressive collagen deposition. Considering the observed data, the MEL-NP developed could be used as a proof of concept to develop a promising strategy for the healing of diabetic wound.

Tumor microenvironment components: Allies of cancer progression.

Cancer is a disease that affects millions of individuals worldwide and has a great impact on public health. Therefore, the study of tumor biology and an understanding of how the components of the tumor microenvironment behave and interact is extremely important for cancer research. Factors expressed by the components of the tumor microenvironment and induce angiogenesis have important roles in the onset and progression of the tumor. These components are represented by the extracellular matrix, fibroblasts, adipocytes, immune cells, and macrophages, besides endothelial cells, which modulate tumor cells and the tumor microenvironment to favor survival and the progression of cancer. The characteristics and function of the main stromal components and their mechanisms of interaction with the tumor cells that contribute to progression, tumor invasion, and tumor spread will be addressed in this review. Furthermore, reviewing these components is expected to indicate their importance as possible prognostic markers and therapeutic targets.