Baccharis anomala DC. extract reduces inflammation and attenuates hepatic fibrosis in vivo by decreasing NF-kB and extracellular matrix compounds.

Baccharis anomala DC. (BA) is a plant species found in the tropical regions of South America and is widely used for its hepatoprotective effects, as well as for the treatment of gastrointestinal diseases. Studies have recently reported its antioxidant and anti-inflammatory potential. BA extract can reverse the activated phenotype of hepatic stellate cells (HSC), which plays a central role in extracellular matrix (ECM) deposition in the development of liver fibrosis. Thus, this study aimed to evaluate the effects of the treatment with BA extract on liver fibrosis in a CCl4-induced liver fibrosis model in BALB/c mice. Methanolic extract was obtained from BA leaves, a gas chromatography/mass spectrometry (GC/MS) to detect the compounds present was performed, and then administered by intraperitoneal injection in Balb/C mice at a concentration of 50 and 100 mg/kg together with the administration of CCl4 for inducing liver fibrosis. After 10 weeks, blood analysis, histopathology, oxidative stress, as well as protein and gene expression in the hepatic tissue were performed. Treatment with BA extract was able to reduce profibrotic markers by reducing the expression of α-SMA and Col-1 proteins, as well as reducing the formation of free radicals and lipid peroxidation. (BA extract showed anti-inflammatory effects in the liver by suppressing NF-kB activation and reducing gene expression of signaling targets (IL-6 and iNOS). The data obtained showed that BA extract has antifibrotic and anti-inflammatory effects.

Bezafibrate reduces the damage, activation and mechanical properties of lung fibroblast cells induced by hydrogen peroxide.

In pulmonary fibrosis, the proliferation of fibroblasts and their differentiation into myofibroblasts is often caused by tissue damage, such as oxidative damage caused by reactive oxygen species, which leads to progressive rupture and thus destruction of the alveolar architecture, resulting in cell proliferation and tissue remodeling. Bezafibrate (BZF) is an important member of the peroxisome proliferator-activated receptor (PPARs) family agonists, used in clinical practice as antihyperlipidemic. However, the antifibrotic effects of BZF are still poorly studied. The objective of this study was to evaluate the effects of BZF on pulmonary oxidative damage in lung fibroblast cells. MRC-5 cells were treated with hydrogen peroxide (H2O2) to induce oxidative stress activation and BZF treatment was administered at the same moment as H2O2 induction. The outcomes evaluated were cell proliferation and cell viability; oxidative stress markers such as reactive oxygen species (ROS), catalase (CAT) levels and thiobarbituric acid reactive substances (TBARS); col-1 and α-SMA mRNA expression and cellular elasticity through Young's modulus analysis evaluated by atomic force microscopy (AFM). The H2O2-induced oxidative damage decreased the cell viability and increased ROS levels and decreased CAT activity in MRC-5 cells. The expression of α-SMA and the cell stiffness increased in response to H2O2 treatment. Treatment with BZF decreased the MRC-5 cell proliferation, ROS levels, reestablished CAT levels, decreased the mRNA expression of type I collagen protein (col-1) and α-smooth muscle actin (α-SMA), and cellular elasticity even with H2O2 induction. Our results suggest that BZF has a potential protective effect on H2O2-induced oxidative stress. These results are based on an in vitro experiment, derived from a fetal lung cell line and may emerge as a possible new therapy for the treatment of pulmonary fibrosis.

CPBMF65, a synthetic human uridine phosphorylase-1 inhibitor, reduces HepG2 cell proliferation through cell cycle arrest and senescence.

Hepatocellular carcinoma (HCC) is the most prevalent type of tumor among primary liver tumors and is the second highest cause of cancer-related deaths worldwide. Current therapies are controversial, and more research is needed to identify effective treatments. A new synthetic compound, potassium 5-cyano-4-methyl-6-oxo-1,6-dihydropyridine-2-olate (CPBMF65), is a potent inhibitor of the human uridine phosphorylase-1 (hUP1) enzyme, which controls the cell concentration of uridine (Urd). Urd is a natural pyrimidine nucleoside involved in cellular processes, such as RNA synthesis. In addition, it is considered a promising biochemical modulator, as it may reduce the toxicity caused by chemotherapeutics without impairing its anti-tumor activity. Thus, the objective of this study is to evaluate the effects of CPBMF65 on the proliferation of the human hepatocellular carcinoma cell line (HepG2). Cell proliferation, cytotoxicity, apoptosis, senescence, autophagy, intracellular Urd levels, cell cycle arrest, and drug resistance were analyzed. Results demonstrate that, after incubation with CPBMF65, HepG2 cell proliferation decreased, mainly through cell cycle arrest and senescence, increasing the levels of intracellular Urd and maintaining cell proliferation reduced during chronic treatment. In conclusion, results show, for the first time, the ability of a hUP1 inhibitor (CPBMF65) to reduce HepG2 cell proliferation through cell cycle arrest and senescence.

Topical chlorhexidine, povidone-iodine and erythromycin in the repair of traumatic ulcers on the rat tongue: Clinical, histological and microbiological evaluation.

OBJECTIVE: This study investigated the effect of topical application of 0.12% chlorhexidine, 10% povidone-iodine and 50% erythromycin on the optimization of healing process of traumatic ulcers made on ventral tongue of rats. DESIGN: Forty-Eight Wistar rats were randomly divided into four groups: control, chlorhexidine (Chx), povidone-iodine (PvI) and erythromycin (Er). An ulcer of 5 mm in diameter was made on the ventral tongue of the animals. After 24 h, a microbiological sample was taken and daily application of the substances started. Six animals each group were euthanized at 4 days and the others at 8 days postoperative, totaling three and seven days of treatment. Prior to euthanasia, a new microbiological collection was performed. RESULTS: The experimental groups showed less area of residual ulcer. A significant difference was seen between the PvI and Chx in relation to the control after three days of treatment (p < 0.05). Although the experimental groups displayed greater newly formed epithelial area, there was no significant difference compared to the control (p > 0.05). Er exhibed the lowest inflammation scores after seven days of treatment (p < 0.05). PvI showed reduction of microorganisms at both times and under aerobic (p < 0.01 at 3 days and p < 0.001 at 7 days) and microaerophilic (p < 0.05) conditions. Er significantly reduced the count of microorganisms in aerobic condition when compared to control group (p < 0.05 at 3 days and p < 0.01 at 7 days). CONCLUSIONS: All drugs promoted reduction of the microorganisms at the site of the injury, which may have a direct effect on the tissue repair process.

Octyl gallate reduces ATP levels and Ki67 expression leading HepG2 cells to cell cycle arrest and mitochondria-mediated apoptosis.

Octyl gallate (OG) is an antioxidant that has shown anti-tumor, anti-diabetic and anti-amyloidogenic activities. Mitochondria play an important role in hepatocellular carcinoma, mainly by maintaining accelerated cellular proliferation through the production of ATP. Thus, the mitochondria may be a target for antitumor therapies. Here, we investigated the effects of OG in the hepatocarcinoma cell line (HepG2) and the mechanisms involved. We report, for the first time, that treatment with OG for 24h inhibited HepG2 cell growth by decreasing mitochondrial activity and mass, which led to the reduction of ATP levels. This reduction in the energy supply triggered a decrease in Ki67 protein expression, leading cells to cycle arrest. In addition, treatment with two doses of OG for 48h induced loss of mitochondrial functionality, mitochondrial swelling and apoptosis. Finally, we report that HepG2 cells had no resistance to treatment after multiple doses. Collectively, our findings indicate that metabolic dysregulation and Ki67 protein reduction are key events in the initial anti-proliferative action of OG, whereas mitochondrial swelling and apoptosis induction are involved in the action mechanism of OG after prolonged exposure. This suggests that OG targets mitochondria, thus representing a candidate for further research on therapies for hepatocarcinoma.

Use of nystatin and chlorhexidine in oral medicine: Properties, indications and pitfalls with focus on geriatric patients.

OBJECTIVES: The aim of this work was to review the scientific literature on the properties, indications and pitfalls related to nystatin and chlorhexidine in oral medicine and also to compare these to other topical antifungal agents, considering the elderly population. BACKGROUND: Nystatin is a polyene antifungal widely used as a topical formulation to treat candidiasis, whereas chlorhexidine is a wide-spectrum antimicrobial, especially used against bacteria, but also effective in treating some fungal infections including those caused by Candida spp. These compounds have been prescribed for immunocompromised patients, hospitalized or not, some of them undergoing head and neck radiation therapy and/or chemotherapy, including elderly patients. MATERIALS AND METHODS: Dental and medical literature concerning the use of nystatin and chlorhexidine in oral medicine were selected and reviewed. RESULTS: Nystatin and chlorhexidine are gold-standard antimicrobial mouthrinses respectively for Candida spp. and bacteria. Although recognized as effective in cotrolling oral infections, both nystatin and chlorhexidine are just complementary to systemic therapy in cases of systemic infections already established. The prescriber should also take into account that some commercial nystatin and chlorhexidine formulations contain compounds such as sugar and ethanol, which can be associated with side effects. Meanwhile, alternative formulations in which these compounds are absent are available and should be considered. CONCLUSIONS: Further studies investigating new drugs and interactions of drug combinations are necessary to improve the therapeutic management of oral infections.