A Lead Target Molecule for Excisional Wound Healing: Trypthantrin Compound.

Objectives: We aimed to evaluate the impact of the tryptanthrin (TRP) compound, with antimicrobial and anti-inflammatory effects, on the excisional wound (EW) model. In an EW model in mice, we tried to explain the possible effect of TRP through vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) that contribute significantly to wound healing. Methods: A total of 90 BALB-C female mice aged 6 - 8 weeks were used in the present study. Animals were randomly divided into five groups. After creating the EW model, three different doses (1, 2.5, 5 mg/kg) of TRP compound were applied topically for 14 days, and wound closure rates were measured on days 0, 3, and 7. Vascular endothelial growth factor and MMP-9 were evaluated on days 3, 7, and 14 on wound explants and on day 14 on serum samples by enzyme-linked immunosorbent assay. Histopathological analysis was performed on wound explants. Results: After the EW model creation, significant healing of the wound areas was observed in the groups for which TRP was applied, especially on the third day. Moreover, in groups that received the third dose of TRP, the wound closure rate was 94%. It was found that the wound areas were closed due to the increase in TRP dose. In line with wound healing, VEGF and MMP-9 levels gradually rose on the third and seventh days and decreased on the 14th day. Conclusions: Tryptanthrin compound usage on the EW model increased wound healing and did not leave a scar after 14 days.

Biochemical Research of the Effects of Essential Oil Obtained from the Fruit of Myrtus communis L. on Cell Damage Associated with Lipopolysaccharide-Induced Endotoxemia in a Human Umbilical Cord Vein Endothelial Cells.

The aim of this study to investigate the potential effects of essential oils and compounds obtained from MC fruit on sepsis induced endothelial cell damage in human umbilical cord vein endothelial cells (HUVECs) at molecular and cellular levels on in vitro sepsis model. A sepsis model was induced by the application of LPS. The HUVEC treatment groups were as follows: control, LPS, MC, MC plus LPS, 1.8 cineole, 1.8 cineole plus LPS, α-pinene, α-pinene plus LPS, α-terpineol, and α-terpineol plus LPS. Following the treatments, cell proliferation was analyzed using the xCELLigence® system. The mRNA expression of various cytokines [tumor necrosis factor (TNF-α), interleukin-1ß (IL-1ß), and IL-6] and endothelial nitric oxide (eNOS) were determined by quantitative polymerase chain reaction (qPCR) analysis. The 1.8 cineole and α-pinene treatments at specific doses showed toxic effects on α-terpineine, although it did not result in a change in the cellular index as compared with that of the control group. The application of LPS to HUVECs led to a significant decrease in the cellular index, depending on the treatment time. It did not correct the decreased cell index of MC plus LPS and α-terpineol plus LPS groups as compared with that of the LPS-only group. The 1.8 cineole plus LPS treatment and α-pinene plus LPS treatment significantly increased the cell index as compared with that of the LPS-only treatment, and the cell index in these groups was closer to that of the control. According to the results of the qPCR analysis, neither the MC-only treatment nor the α-terpineol-only treatment significantly reduced cellular damage caused by LPS-induced increases in TNF-α, IL-1ß, IL-6, and eNOS mRNA expression. However, both the 1.8 cineole treatment and α-pinene treatments significantly decreased TNF-α, IL-1ß, IL-6, and eNOS mRNA expression induced by LPS. Volatile oil obtained from MC fruit and the MC compound α-terpineol had no effect on the decreased cell index and increased cytokine response due to LPS-induced endothelial cell damage. However, 1.8 cineole and α-pinene, other major components of MC fruit, ameliorated LPS-induced damage in HUVECs at cellular and biomolecular levels (TNF-α, IL-1ß, IL-6, and eNOS).

Effects of Aliskiren, an RAAS inhibitor, on a carrageenan-induced pleurisy model of rats.

Our aim is to investigate the potentially preventive effects of Aliskiren in a carrageenan-induced lung pleurisy model and to compare the standard anti-inflammatory agents, indomethacin and dexamethasone. The pleurisy model was induced through the injection of carrageenan (0.2 ml-%2) into the pleural cavity. After the experiment, serum and lung tissues were collected and biochemical, molecular and pathological examinations were performed. In our study, pleural inflammation decreased superoxide dismutase activity and the glutathione level and increased the malondialdehyde level in the lung of rats, while Aliskiren increased the superoxide dismutase activity and glutathione level and decreased the malondialdehyde level. In addition, carrageenan-induced pleurisy caused a significant increase in pro-inflammatory cytokines mRNA expressions (TNF-α, IL-1ß, and NF-KB), while Aliskiren administration decreased their expressions as well as the standard treatments, indomethacin and dexamethasone, did. Aliskiren administration at the 200 mg/kg dose protected the lungs in the pathological evaluation, especially against inflammatory cell infiltration and edematous lesions. It appears that Aliskiren protects the lung from carrageenan-induced pleurisy damage by regulating inflammation and antioxidant-oxidant balance via Renin Angiotensin Aldosterone System inhibition.

A novel approach to contrast-induced nephrotoxicity: the melatonergic agent agomelatine.

OBJECTIVE: To study the potential nephroprotective role of agomelatine in rat renal tissue in cases of contrast-induced nephrotoxicity (CIN). The drug's action on the antioxidant system and proinflammatory cytokines, superoxide dismutase (SOD) activity, levels of glutathione (GSH) and malondialdehyde (MDA) and the gene expression of interleukin-6 (IL-6), tumour necrosis factor (TNF)-α and nuclear factor kappa B (NF-κB) was measured. Tubular necrosis and hyaline and haemorrhagic casts were also histopathologically evaluated. METHODS: The institutional ethics and local animal care committees approved the study. Eight groups of six rats were put on the following drug regimens: Group 1: healthy controls, Group 2: GLY (glycerol), Group 3: CM (contrast media--iohexol 10 ml kg(-1)), Group 4: GLY+CM, Group 5: CM+AGO20 (agomelatine 20 mg kg(-1)), Group 6: GLY+CM+AGO20, Group 7: CM+AGO40 (agomelatine 40 mg kg(-1)) and Group 8: GLY+CM+AGO40. The groups were evaluated by one-way analysis of variance and Duncan's multiple comparison test. RESULTS: Agomelatine administration significantly improved the serum levels of blood urea nitrogen (BUN) and creatinine, SOD activity, GSH and MDA. The use of agomelatine had substantial downregulatory consequences on TNF-α, NF-κB and IL-6 messenger RNA levels. Mild-to-severe hyaline and haemorrhagic casts and tubular necrosis were observed in all groups, except in the healthy group. The histopathological scores were better in the agomelatine treatment groups. CONCLUSION: Agomelatine has nephroprotective effects against CIN in rats. This effect can be attributed to its properties of reducing oxidative stress and inhibiting the secretion of proinflammatory cytokines (NF-κB, TNF-α and IL-6). ADVANCES IN KNOWLEDGE: CIN is one of the most important adverse effects of radiological procedures. Renal failure, diabetes, malignancy, old age and non-steroidal anti-inflammatory drug use pose the risk of CIN in patients. Several clinical studies have investigated ways to avoid CIN. Theophylline/aminophylline, statins, ascorbic acid and iloprost have been suggested for this purpose. Agomelatine is one of the melatonin ligands and is used for affective disorders and has antioxidant features. In this study, we hypothesized that agomelatine could have nephroprotective, antioxidant and anti-inflammatory effects against CIN in rats.