Objective: To evaluate the effect of resveratrol against CCl4-induced nephrotoxicity. Methods: Forty-two male Wistar rats were divided into seven groups randomly. After six weeks, kidney weight, body weight, blood urea, serum creatinine, oxidative stress markers, and gene expression of renal transforming growth factor-beta1 (TGF-β1), TGF-β receptor type 1 (TGF-βR1) and Smad3 were determined. In addition, the protein level of TGF-β1 in the tissue lysate was measured. Results: Resveratrol had a protective role in renal tissue by the improvement of antioxidant balance and reduction of renal parameters such as creatinine and urea (P<0.001). In addition, the renal mRNA level of TGF-β1, TGF-βR1, Smad3, as well as the protein level of TGF-β1 were decreased in rats treated with resveratrol (P<0.001), compared to the CCl4 group. Conclusions: Overall, resveratrol shows a protective effect against nephrotoxicity in CCl4 treated rats by reducing oxidative stress status and modulating the TGF-β signaling.

Betatrophin is a newly characterized circulating hormone that is produced in tissues such as adipose tissue and liver and stimulates pancreatic beta-cell proliferation. The purpose of the current study was to examine circulating betatrophin levels in Iranian patients with type 2 diabetes mellitus (T2DM) and in normal controls. Seventy-five subjects were enrolled in this case-control study in the following two groups: T2DM patients (n=40) and a group of age-, sex-, and BMI-matched normal control subjects (n=35). Circulating betatrophin concentrations as well as the blood lipid profile, body mass index (BMI), fasting blood sugar (FBS), glycated hemoglobin (HbA1c), and insulin resistance were determined. Circulating betatrophin levels were significantly higher in patients with T2DM than in the normal subjects (4.79+/-1.53 ng/mL vs. 2.79+/-1.11 ng/mL respectively; p=0.001). Serum triacylglycerol and total cholesterol were also significantly higher in patients with T2DM than in the control group. In the patients with T2DM, serum betatrophin was positively correlated with age, FBS, TG, total cholesterol, and HbA1c. The results of this initial study in Iran have shown that circulating betatrophin levels are significantly increased in Iranian patients with T2DM compared with a control group. Additionally, it is postulated that betatrophin as a novel hormone may be involved in the generation of an atherogenic lipid profile.
Adipose Tissue ; Blood Glucose ; Body Mass Index ; Case-Control Studies ; Cholesterol ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Fasting ; Hemoglobin A, Glycosylated ; Humans ; Insulin Resistance ; Iran ; Liver ; Triglycerides

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

Contrast-induced acute kidney injury (CI-AKI) is a frequent challenge following the injection of contrast media and its subsequent oxidative stress. The aim of the present study was to evaluate the preventive effects of coenzyme Q10 (Q10), as a mitochondrial-targeted antioxidant in CI-AKI in diabetic patients, who account for a large proportion of angiographic cases. A total of 118 diabetic patients were randomly assigned to receive 120 mg of oral coenzyme Q10 (Q10 group) or placebo (Placebo group) for four days, starting 24 hours before contrast media injection. Blood urea nitrogen (BUN), serum and urinary creatinine, estimated glomerular filtration rate (eGFR), urinary malondialdehyde (UMDA), urinary total antioxidant capacity (UTAC), and urinary mitochondrial to nuclearDNA ratios (mtDNADNA ratio) were evaluated before and after the treatment period. Urine sediments were also evaluated to report the urine microscopy score (UMS).The levels of BUN, serum and urine creatinine, and UMS were similar in the Q10 and placebo groups. EGFR was lower in the Q10 group before the treatment (p=0.013) but not after. The urinary mtDNADNA ratio was 3.05±1.68 and 3.69±2.58 in placebo and Q10 groups, but UTAC was found to be lower in Q10 both before (p=0.006) and after the treatment (p＜0.001). The incidence of CI-AKI was 14.40% and the mtDNANDA ratio was similar between CI-AKI and non-CI-AKI patients. In conclusion, Q10 treatment shows no favorable effect on prevention of CI-AKI or a urinary mtDNADNA ratio among diabetic patients.

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.

Objective: To evaluate the effect of resveratrol against CCl