Serum and Tissue HIF-2 Alpha Expression in CIN, N-Acetyl Cysteine, and Sildenafil-Treated Rat Models: An Experimental Study.

Background and Objectives: Contrast-induced nephropathy (CIN), is acute renal damage due to contrast agents. This study is conducted to evaluate serum and renal heterodimeric nuclear transcription factor (HIF)-2 alpha levels and its tissue expression in contrast-induced nephropathy, and in N-acetyl cysteine (NAC)-and Sildenafil-treated rat models. Materials/Methods: This randomized, controlled, interventional animal study was conducted on Wistar rats. Rats (n = 36) were randomly assigned to four groups: control (n = 9), CIN group (n = 9), CIN + NAC group (n = 9), and sildenafil (n = 9). The rat model was used to form iohexol-originated CIN. During the modeling, prophylactic treatment was performed at the 24th and 48th h. After 48 h of modeling, blood, urine, and tissue samples were obtained for biochemical analyses. HIF-2-α levels were measured in renal tissue, serum, and urine samples. Renal sections were also performed for histopathologic and immunohistochemical evaluations of renal injury and HIF-2-α expression. Results: In the CIN model, HIF-2α levels and other biochemical parameters were significantly increased (p < 0.01). Both sildenafil and NAC efficiently decreased renal damage due to contrast agents, as shown in histopathologic examinations (p < 0.05). Similarly, after treatment with sildenafil and NAC, HIF-2α levels were significantly decreased (p < 0.05). Conclusions: The current study shows that serum and tissue HIF-2α levels decrease in CIN. Besides, the levels and tissue expression of HIF-2α decrease with both NAC and sildenafil treatments. With further studies, HIF-2α can be investigated as a biomarker of CIN and can be used in the follow-up of patients with CIN.

Lycopene Ameliorates Experimental Colitis in Rats via Reducing Apoptosis and Oxidative Stress.

Inflammatory bowel disease (IBD) is an inflammatory disorder involving colitis. Lycopene is a naturally occurring carotenoid that has attracted considerable attention as a potential chemopreventive agent. The impact of lycopene on colitis is currently unknown. The aim of this study was to investigate the protective effects of lycopene in a rat model of colitis induced by acetic acid. The animals were randomly divided into the following five groups: the control group, colitis group, colitis + sulfasalazine group as a positive control group, colitis + lycopene and lycopene groups. Colonic mucosal injury was assessed by biochemical and histopathological examinations. Malondialdehyde (MDA), superoxide dismutase (SOD) activity, total antioxidant status (TAS), ceruloplasmin (CPN), total sialic acid and iron (Fe) levels were evaluated in blood samples. MDA, SOD, TAS and DNA fragmentation levels were also measured in colon tissues. MDA (p < 0.05), total sialic acid (p < 0.05) and DNA fragmentation levels (p < 0.01) were significantly higher, and the activity of the antioxidant enzyme were lower in the colitis group than in the control group. Treatments with lycopene in the colitis decreased MDA, total sialic acid and DNA fragmentation levels, while SOD activity (p < 0.05), TAS (in colon p < 0.05; in serum p < 0.01), CPN (p < 0.05) and Fe levels (p < 0.05) were significantly increased. The histopathological evaluation also confirmed the foregoing findings. Treatment with lycopene ameliorated the biochemical and pathological alterations caused by colitis. The results obtained in this study indicate that lycopene may exert protective effects in experimental colitis and might, therefore, be useful for treatment of IBD.

Investigating the anti-tumoral effect of yarrow (Achillea milllefolium) on the mice in which ehrlich solid tumor is created.

In this study, BALB/c mice with Ehrlich solid tumors were used to examine the effect of Achillea millefolium L. (AM) extract on the Ehrlich ascites tumor (EAT) model, which is one of the experimental cancer models. Also known as yarrow and plant, AM has antioxidant, anti-inflammatory, antibacterial and antitumor properties. In our study, 57 male BALB/c type mice, 8-10 weeks old, weighing 25-30 g, were used. Mice were divided into two groups. Ehrlich Solid Tumor group: Negative Control Group (ENC), Positive Control Group (EPC), and Treatment Group (TG) (TNCAM-200 mg/kg, TPCAM-400 mg/kg). EPC and TG were given to EAT cells. Each EAT contained 1 × 106 (will be 6 out of 10: so:000000) EAT cells, 0.1 ml of phosphate-buffered saline (PBS) was administered subcutaneously (s.c.) to the nape of mice. Then It was awaited for solid tumor formation. AM extract was administered intraperitoneally (i.p.) to TG for 17 days to mice. AM extract was found to have a curative effect on areas of inflammation, bleeding, and necrosis in treatment groups treated with AM extract alone. The treatment groups showed nearly normal histological results compared to the positive control group. According to the results, the TPCAM-400 mg/kg group had a more significant histological impact than the TNCAM-200 mg/kg group. In terms of tumor growth, tumor length, tumor volume, and tumor weight, AM extract did not show significant effects. However, in the light of histological findings, promising results of AM were observed in mice in which Ehrlich Solid Tumor was formed.

Effect of kirenol on the interaction between the WNT/ß-Catenin and RUNX2/TCF/LEF1 pathways in fracture healing in vivo.

OBJECTIVE: This study aimed to determine the effects of a natural diterpenoid, kirenol, on fracture healing in vivo in an experimental rat model of femur fracture and investigate its potential mechanism of action via the Wnt/ß-catenin pathway. METHODS: In this study, 64 male Wistar albino rats aged 5-7 weeks and weighing 261-348 g were randomly divided into 8 groups from A to L, with eight rats in each group. Standardized fractures were created in the right femurs of the rats and then fixed with an intramedullary Kirschner wire. Four experimental groups were administered 2 mg/kg/day kirenol (Groups C and G) and 4 mg/kg/day (Groups D and H) kirenol by oral gavage.Thereafter, the animals were sacrificed at two time points as follows: on the 10th day (Groups B, C and D) and on the 21st day (Groups F, G and H) after the surgery; fracture healing in each group was assessed radiologically and histopathologically. The Radiographic Union scale of tibia fracture scoring system was used in the radiological examination; callus volume and density were measured using computed tomography. In the histopathologic examination, the scoring system described by Huo et al. was used. Additionally, the mechanism of action was evaluated based on the analyses of protein expression of Wnt3a, LRP5, TCF-LEF1, ß-catenin, and Runx-2 proteins using western blot analysis. RESULTS: Among the animals sacrificed on the 10th day after the surgery, the highest histopathological and radiological scores were observed in Group D (p<0.05). Furthermore, the callus density (p<0.05) was highest in Group D. Among the animals sacrificed on the 21st day, the highest histopathological and radiological scores were found in Group H, although the differences among the groups were not significant (p>0.05). The callus volume and density were the highest in Groups G and H, respectively, although the differences among groups were not significant. CONCLUSION: Kirenol may improve fracture healing in a dose-dependent manner with the early activation of the Wnt/ß-catenin pathway and the activation of the Runx-2 pathway.