Purpose:This study aimed to investigate radiation-induced lesions on the skin in an experimental animal model. Methods and Materials: Cutaneous wounds were induced in Wistar rats by 4 MeV energy electron beam irradiation, using a dose rate of 240 cGy/min, for 3 different doses (10 Gy, 40 Gy, and 60 Gy). The skin was observed 5, 10, and 25 days (D) after ionizing radiation exposition.Results:Infiltrate inflammatory process was observed in D5 and D10, for the 40 Gy and 60 Gy groups, and a progressive increase of transforming growth factor β1 is associated with this process. It could also be noted a mischaracterization of collagen fibers at the high-dose groups.Conclusion:It was observed that the lesions caused by ionizing radiation in rats were very similar to radiodermatitis in patients under radiotherapy treatment.Advances in Knowledge:This study is important to develop strategies to prevent radiation-induced skin reactions.

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Adipose-derived mesenchymal stromal cell (AD-MSC) administration improves cardiac function after acute myocardial infarction (AMI). Although the mechanisms underlying this effect remain to be elucidated, the reversal of the mitochondrial dysfunction may be associated with AMI recovery. Here, we analyzed the alterations in the respiratory capacity of cardiomyocytes in the infarcted zone (IZ) and the border zone (BZ) and evaluated if mitochondrial function improved in cardiomyocytes after AD-MSC transplantation. Female rats were subjected to AMI by permanent left anterior descending coronary (LAD) ligation and were then treated with AD-MSCs or PBS in the border zone (BZ). Cardiac fibers were analyzed 24 hours (necrotic phase) and 8 days (fibrotic phase) after AMI for mitochondrial respiration, citrate synthase (CS) activity, F0F1-ATPase activity, and transmission electron microscopy (TEM). High-resolution respirometry of permeabilized cardiac fibers showed that AMI reduced numerous mitochondrial respiration parameters in cardiac tissue, including phosphorylating and nonphosphorylating conditions, respiration coupled to ATP synthesis, and maximal respiratory capacity. CS decreased in IZ and BZ at the necrotic phase, whereas it recovered in BZ and continued to drop in IZ over time when compared to Sham. Exogenous cytochrome c doubled respiration at the necrotic phase in IZ. F0F1-ATPase activity decreased in the BZ and, to more extent, in IZ in both phases. Transmission electron microscopy showed disorganized mitochondrial cristae structure, which was more accentuated in IZ but also important in BZ. All these alterations in mitochondrial respiration were still present in the group treated with AD-MSC. In conclusion, AMI led to mitochondrial dysfunction with oxidative phosphorylation disorders, and AD-MSC improved CS temporarily but was not able to avoid alterations in mitochondria function over time.

Radiation-induced liver disease (RILD) remains a major problem resulting from radiotherapy. In this scenario, immunotherapy with granulocyte colony-stimulating factor (G-CSF) arises as an attractive approach that might improve the injured liver. Here, we investigated G-CSF administration’s impact before and after liver irradiation exposure using an association of alcohol consumption and local irradiation to induce liver disease model in C57BL/6 mice. Male and female mice were submitted to a previous alcohol-induced liver injury protocol with water containing 5% alcohol for 90 days. Then, the animals were treated with G-CSF (100 μg/kg/d) for 3 days before or after liver irradiation (18 Gy). At days 7, 30, and 60 post-radiation, non-invasive liver images were acquired by ultrasonography, magnetic resonance, and computed tomography. Biochemical and histological evaluations were performed to verify whether G-CSF could prevent liver tissue damage or reverse the acute liver injury. Our data showed that the treatment with G-CSF before irradiation effectively improved morphofunctional parameters caused by RILD, restoring histological arrangement, promoting liver regeneration, preserving normal organelles distribution, and glycogen granules. The amount of OV-6 and F4/80-positive cells increased, and α-SMA positive cells’ presence was normalized. Additionally, prior G-CSF administration preserved serum biochemical parameters and increased the survival rates (100%). On the other hand, after irradiation, the treatment showed a slight improvement in survival rates (79%) and did not ameliorate RILD. Overall, our data suggest that G-CSF administration before radiation might be an immunotherapeutic alternative to radiotherapy planning to avoid RILD.

Some chemotherapeutic agents used for breast cancer (BC) treatment can induce severe side effects in the ovarian tissue. The combination of cyclophosphamide and docetaxel (TC) is widely used for BC treatment; however, its late effects in the ovary are not completely understood. The main purpose of this study was to evaluate the structural and ultrastructural alterations in the ovarian stroma induced by TC treatment. Wistar rats were divided into two groups: a control group and a TC group. They were euthanized 5 months after the end of treatment, and their plasma and ovaries were collected. Important alterations were noted. The serum estradiol level was significantly reduced in the TC group compared with the control group. Additionally, the number of apoptotic nuclei was higher in the TC group. The role of the inflammatory response in the development of ovarian damage was investigated, and we found an increased number of mast cells and increased expression of TNF-α in the TC group. The involvement of fibrosis was also investigated. The results showed that the TC group had increased expression levels of TGF-β1, collagen type I (col-I) and collagen type III (col-III) compared with the control group. Ultrastructural analysis revealed the presence of collagen fibrils in the treated group and illustrated that the ovarian tissue architecture was more disorganized in this group than in the control group. The results from this study are important in the study of chemotherapy-induced ovarian failure and provide further insight into the mechanisms involved in the development of this disease.

Hypertension is a disease classified as primary or secondary, manifested not only by elevation of blood pressure but also involved in structural and functional changes of target organs. Renal artery stenosis is a leading factor of secondary hypertension, and its progress is associated with overactivation of the renin-angiotensin-aldosterone system (RAAS). Aliskiren is a renin inhibiting drug that suppresses RAAS and culminates in decreased renin release, plasma angiotensin II concentration, and inhibition of aldosterone secretion. In this sense, the aim of the present study was to analyze the structural and ultrastructural morphophysiology of the adrenal glomerular zone, after treatment with aliskiren in Wistar rats with 2K1C hypertension. Parameters as structure and ultrastructure of the adrenal glomerular zone, cellular apoptosis, nuclear cell proliferation, and AT1 receptor expression were analyzed by immunostaining and electron microscopy. Our results showed that the hypertensive animals treated with aliskiren presented a reestablishment of AT1 receptor expression and decrease in apoptosis and autophagy. In addition, treatment with aliskiren improves the cell aspects in the adrenal glomerular zone, evidenced by ultrastructural analysis through preserved nuclei and well-developed mitochondria. Therefore, our evidence suggests that aliskiren has a beneficial effect on the adrenal glomerular zone remodeling in animals with renovascular hypertension.

Obesity is an inflammatory disease associated with secondary diseases such as kidney disease, which can cause lipotoxicity, inflammation and loss of organ function. Polyunsaturated fatty acids act in the production of lipid mediators and have anti-inflammatory characteristics. In this work, the objective was to evaluate renal histopathology in obese mice and the effects of treatment with capybara oil (CO) (5000 mg/kg/day for 4 weeks). Parameters such as body mass, lipid profile, systolic blood pressure, urinary creatinine and protein excretion, structure and ultrastructure of the renal cortex, fibrosis, tissue inflammation and oxidative stress were analyzed. CO treatment in obese mice showed improvement in the lipid profile and reduction in systolic blood pressure levels, in addition to beneficial remodeling of the renal cortex. Our data demonstrated that CO decreased inflammation, oxidative stress and renal fibrosis, as evidenced by quantifying the expression of TNF-α, IL-10, CAT, SOD, α-SMA and TGF-β. Although treatment with CO did not show improvement in renal function, ultrastructural analysis showed that the treatment was effective in restoring podocytes and pedicels, with restructuring of the glomerular filtration barrier. These results demonstrate, for the first time, that treatment with CO is effective in reducing kidney damage, being considered a promising treatment for obesity.