Nilotinib as a tyrosine kinase inhibitor has been recently used to improve the liver fibrosis process, but the exact mechanisms still require further clarification. In this study, we investigated the anti-fibrotic effects of Nilotinib via RAGE/HMGB1axis and antioxidant mechanisms. This experimental study was performed in the Hamadan University of Medical Sciences, Iran, from May 2015 to December 2016. Liver fibrosis was induced in Wistar male rats by CCL₄. Rats were gavaged daily with Nilotinib (10 mg/kg). RAGE, HMGB1, TNF-α and TGF-β mRNA expression were evaluated by quantitative RT-PCR. TNF-α protein levels were measured using the immunoassay method. Thiol groups, carbonyl groups, nitric oxide levels and glutathione peroxidase activity were measured by spectrophotometric methods.The results showed that Nilotinib decreased TNF-α, TGF-β, RAGE and HMGB1 mRNA expression (p<0.001) in the liver tissues of the fibrosis group. Nilotinib also decreased carbonyl groups and nitric oxide levels and increased thiol groups and glutathione peroxidase activity in the fibrosis groups. The histopathological changes were found to be attenuated by Nilotinib. In conclusion, Nilotinib can improve liver fibrosis and open new mechanisms of the anti-fibrotic properties of Nilotinib.
Animals ; Fibrosis ; Gene Expression ; Glutathione Peroxidase ; HMGB1 Protein ; Humans ; Immunoassay ; Iran ; Liver Cirrhosis ; Liver ; Male ; Methods ; Nitric Oxide ; Oxidative Stress ; Protein-Tyrosine Kinases ; Rage ; Rats ; RNA, Messenger

Regulation of the peroxisome proliferator-activated receptor-γ (PPAR-γ) gene plays an important role in controlling the metabolism of lipids and inflammatory processes. Therefore, it can be associated with the pathogenesis of metabolic syndrome (MetS). The purpose of this study was to determine the expression of this gene in peripheral blood mononuclear cells (PBMC) in patients with metabolic syndrome. Using real-time polymerase chain reaction (PCR), mRNA expression of PPAR-γ was found in PBMC from 37 subjects with MetS and 30 healthy controls. Serum levels of glucose and lipid profiles were measured. The total antioxidant capacity (TAC) was measured using the ferric reducing ability of plasma (FRAP) test. Malondialdehyde (MDA) was determined using a fluorimetric method. Total oxidant status (TOS) in serum was assayed according to oxidation of ferric to ferrous in the presence of methyl orange. Super oxide dismutase (SOD) activity was measured using a Randox kit. Expression of PPAR-γ gene was significantly increased in patients with MetS compared to the control subjects (p=0.002). There was no difference in serum levels of TAC, MDA and SOD between the two study groups, but a significant difference was observed in the TOS (p=0.03). Serum levels of triglycerides and glucose were significantly higher in subjects with MetS. According to the results of our study, an increase in the expression of PPAR-γ in subjects with MetS indicated a possible role of PPAR-γ in the pathogenesis of this disease.
Citrus sinensis ; Gene Expression ; Glucose ; Humans ; Malondialdehyde ; Metabolism ; Methods ; Oxidative Stress ; Peroxisomes ; Plasma ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; Triglycerides

Objective: To evaluate the antiglycation and antioxidant properties of the dill tablet, an herbal product used in Iran as a hypolipidemic medicine. Methods: In this descriptive study, the antioxidant and antiradical properties of dill tablet at different concentration (0.032, 0.065, 0.125, 0.25, 0.5 and 1 mg/mL) were measured. The total phenolic, flavonols and flavonoid, alkaloids, anthocyanin, tannin and saponin contents in dill tablet were determined. Furthermore, antiglycation properties of dill tablet were assayed. In the in vivo experiments, male rats were randomly divided into three groups (n = 6): Group 1: normal rats; Group 2: diabetic rats; Group 3: diabetic rats + 300 mg/kg dill tablet, and Group 4: diabetic rats + 100 mg/kg dill tablet. After 2 months, the blood glucose was measured enzymatically and advanced glycation end-products (AGEs) formation was determined using a fluorometric method. Results: Our results illustrated that different concentrations of dill tablet had significant antioxidant activity. Dill tablet markedly declined AGEs formation and fructosamine levels (P < 0.001) compared with glycated sample. Oxidation of protein carbonyl and thiol group was significantly reduced by dill tablet in a dose dependent manner (P < 0.001). Formation of amyloid cross-β and fragmentation were markedly inhibited by dill tablet (P < 0.001) compared with glycated sample. After 2 months, fasting blood glucose levels (P < 0.001) and AGEs formation (P < 0.05) were significantly reduced by dill tablet in diabetic animals. Conclusions: Dill tablet exhibited significant antiglycation and antioxidant activities. This study provides a scientific basis for using dill in treatment of diabetic patients.

OBJECTIVES: Assessment of dental pain severity is very challenging in dentistry. Previous studies have suggested that elevated salivary alpha amylase may contribute to increased physical stresses. There is a close association between salivary alpha amylase and plasma norepinephrine under stressful physical conditions. The aim of this study was to evaluate the relationship between pain severity and salivary alpha amylase levels in patients with symptomatic irreversible pulpitis. MATERIALS AND METHODS: Thirty-six patients (20 females and 16 males) with severe tooth pain due to symptomatic irreversible pulpitis were selected. The visual analogue scale (VAS) score was used to assess the pain severity in each patient. Unstimulated whole saliva was collected, and the level of alpha amylase activity was assessed by the spectrophotometric method. Statistical analysis was performed using SPSS 13. RESULTS: The level of alpha amylase was significantly increased in the saliva in association with pain severity assessed by VAS. The salivary alpha amylase was also elevated with increased age and in males. CONCLUSIONS: There was a significant correlation between the VAS pain scale and salivary alpha amylase level, which indicates this biomarker may be a good index for the objective assessment of pain intensity.
alpha-Amylases ; Dentistry ; Female ; Humans ; Norepinephrine ; Plasma ; Pulpitis ; Saliva ; Tooth

Oral lichen planus (OLP) is a chronic inflammatory mucosal disease of unknown etiology. Many studies have implicated the protective role of antioxidants in such diseases. The aim of this study was to compare salivary total antioxidant capacity (TAC and malondialdehyde (MDA) and antioxidant vitamin (vitamin s A, C and E) levels in patients with erosive OLP and healthy individuals. Thirty six patients with OLP (14 males, 22 females) and 36 control subjects (15 males, 21 females), matched for age and sex were enrolled in this case control study. The salivary levels of MDA, TAC, and antioxidant vitamin levels were measured in both case and control groups. The salivary level of MDA was significantly higher (p<0.001) in patients than in controls. In patients with OLP, the TAC of saliva was significantly lower than that in healthy subjects (p<0.001). Compared with controls, the levels of salivary antioxidant vitamins were significantly decreased in patients with OLP (p<0.001). In addition, a positive correlation was found between the decrease in the salivary amount of vitamin C and that in vitamin E in patients and controls. In addition to the lower salivary levels of antioxidant vitamins and the lower TAC, the higher level of MDA in patients with OLP suggests that free radicals and the resulting oxidative damage may be important in the pathogenesis of OLP lesions.
Antioxidants ; Ascorbic Acid ; Case-Control Studies ; Free Radicals ; Humans ; Lichen Planus, Oral ; Lipid Peroxidation ; Male ; Malondialdehyde ; Oxidative Stress ; Saliva ; Vitamin E ; Vitamins