Bone development in offspring of pregnant rats treated with carbamazepine: Evaluation by three different methods.

OBJECTIVE: This study was carried out to determine the effect of intrauterine carbamazepine (CBZ) exposure on fetal bone development during pregnancy. METHODS: In the study, 24 female Wistar pregnant rats were used. Rats were 20 weeks old. They had an average body weight of 150-200 g. Pregnant rats were randomly selected and divided (n = 6) into a control group, low-dose CBZ (10 mg/kg/day) group, medium-dose CBZ (25 mg/kg/day) group, and high-dose CBZ (50 mg/kg/day) group. The ossification length (mm) and ossification area (mm2 ) of the long bones of the fetuses in the experimental and control groups were calculated. The densities of alkaline phosphatase (AP) and tartrate-resistant acid phosphatase (TRAP) were analyzed. The ossification regions of the femurs of the fetuses were examined under a light microscope. Microstructural images of the femurs were evaluated with scanning electron microscope photographs. The densities of minerals involved in the ossification process were analyzed. RESULTS: According to the results of the study, all three doses of CBZ caused loss of ossification areas, and it was observed that this bone loss also increased statistically significantly depending on the dose increase (p < .05). Calcium concentration decreased in the CBZ groups. When the electron microscope images were examined, it was determined that the cartilage matrix of the CBZ groups was thinned. In the histological evaluation of the groups, narrowing of the primary bone collar and smaller bone spicules in the ossification region compared to the control group were noted due to the increase in dose in the CBZ groups. In immunohistochemical staining, it was observed that the TRAP and AP expression values of the femurs were the lowest in the CBZ groups. These decreases were also statistically significant when compared with the control group. SIGNIFICANCE: It was revealed with both microscopic and macroscopic findings that exposure to intrauterine CBZ negatively affected ossification and bone growth.

The effect of antioxidants in Ehrlich Ascites Cancer.

A fundamental goal in molecular oncology is to unravel the underlying mechanisms which cause the cell transformation. In line with this approach, genome-wide functional screening approaches have revealed exciting insights into heterogeneous nature of cancer. Rapidly expanding horizons of research have unraveled myriad of pathways which play instrumental role in carcinogenesis and metastasis. Oxidative stress has also been reported to be significantly involved in cancer onset and progression. In line with this approach, oxidative stress modulating chemicals have always been sharply divided into antioxidants and oxidative stress-inducing agents. Conceptual and experimental advancements have enabled us to critically analyze full potential of these two different groups of chemicals in cancer chemoprevention. Different antioxidants are currently being analyzed in different phases of clinical trials. Although it has been reported in the literature that antioxidant supplements reduce tumor cells in some tumors or cause volume reduction in solid tumor sizes, there is no definite consensus. Therefore, an antioxidant supplement guideline based on more detailed clinical research and as a result of these is needed to achieve the best care for cancer patients and to avoid risky treatments for cancer patients.

The protective role of melatonin against the effects of different doses of caffeine on the fetus.

Skeletal system and some organs development changes in rat fetuses with 30 and 60 mg/kg caffeine and melatonin's (10 mg/kg) protective role against rat fetuses were investigated. Groups (n = 4) were formed as Control, LDC, HDC, LDC+melatonin, HDC+melatonin and melatonin. Fetuses were taken by cesarean section and stained using dual skeletal staining method and FESEM. TRAP and AP immune-reactivity concentrations were calculated.  Oxidative stress and inflammatory markers were also measured by liver, bone and placenta samples.  TNF-α, IL-1ß, IL-6, VEGF-A, SOST and Fetuin-A levels were measured in tissue by using ELISA. TBARS, SOD, GSH, GSSG, TOS, TAS, measured by spectrophotometric assay method.  The mRNA levels of Agtr2 gene expressed in placental tissues of control rats and in placental tissues of rats exposed to HDC, LDC, MEL, HDC+MEL, LDC+MEL were analyzed by Real-time PCR. The gene expressions of Agtr2 were significantly upregulated in the placentas exposed to HDC, MEL, HDC+MEL and LDC+MEL (P<0,001). No significant difference in samples of the LDC group (P>0,05). According to these data, caffeine used during pregnancy delayed ossification; melatonin, a powerful antioxidant, was found to eliminate this effect. Besides, changes in angiotensin receptor expression observed in response to a caffeine and melatonin exposure result from high dose and join effect.

Antioxidant role of melatonin against nicotine's teratogenic effects on embryonic bone development.

OBJECTIVES: This study investigated the possible effects of low (3 mg/kg) and high (6 mg/kg) doses of nicotine on the skeletal development of rat fetuses by the double staining method and the protective role of melatonin (10 mg/kg) against these effects. MATERIALS AND METHODS: Eighteen adult female Wistar-Albino rats were divided into six groups (n=3, each) as control, low-dose nicotine, high-dose nicotine, low-dose nicotine+melatonin, high-dose nicotine + melatonin and melatonin. While nicotine was given to the experimental groups on gestation days 1-20, nicotine and melatonin were administered together to the treatment groups. The fetuses were delivered by cesarean section on the 20th day of pregnancy. The skeletal systems of the fetuses were stained using the double staining method. The forelimbs and hindlimbs of the fetuses were firstly investigated under a stereomicroscope, and then their photos were taken. The total bone length, the length of the ossified part and the ossification rate were calculated using the ImageJ program. RESULTS: The degree of ossification in the bones of the feet and the hands was determined. When the total bone length and the length of the ossified part were evaluated, they were significantly decreased in the nicotine groups (P<0.05), but were close to each other in the treatment and the control groups (P<0.05). CONCLUSION: It has been found that the use of nicotine during pregnancy delays skeletal ossification and that melatonin, a powerful antioxidant, eliminates the teratogenic effects of nicotine.

The effects of gilaburu (Viburnum opulus) juice on experimentally induced Ehrlich ascites tumor in mice.

OBJECTIVE: The aim of study was to investigate anticancer effect of Viburnum opulus (VO) on Ehrlich ascites carcinoma (EAC) bearing mice that treated with different concentrations of VO. MATERIALS AND METHODS: For tumor transplantation; mice were inoculated with 1 × 106 EAC cells intraperitoneally and than divided into five groups (n = 9). Two hours after inoculation; experimental groups were treated daily with VO extract at doses of 1000 mg/kg, 2000 mg/kg, 4000 mg/kg. RESULTS: Extracts obtained from gilaburu juice can have hinder effect on tumor cell growth. CONCLUSION: As far as we known, this is the first study about in vivo antitumoral activity of VOon Ehrlich ascites tumor model, and consequently VO extract exhibited anticancer activity against EAC-bearing mice.