Hyperthermia alters neurobehavior by affecting cell proliferation and neuronal survival in young male rats.

Maintenance of body temperature within physiological range is critical for the fetal and neonatal development. Hyperthermia is one of the most frequently encountered pediatric complaints and may cause neurological disorders due to neuronal injury. In this study, we aimed to investigate the effects of hyperthermia on behavioral alterations, neuronal survival, apoptosis, and cell proliferation in young male Sprague-Dawley rats. Twenty-one 13-day-old rats were randomly divided into three groups (n = 7 per group). Body temperature was increased to 39°C and 41°C in a hyperthermia induction chamber for 30 min, whereas the animals in control group were maintained at 36°C. Twenty-four hours after hyperthermia, animals were subjected to the open field test, elevated-O-maze test, and grip strength test to assess the locomotor activity, anxiety, and motor function. Neuronal survival, apoptosis, and cell proliferation were investigated in cortex, hippocampal dentate gyrus (DG) and CA1 regions, and corpus callosum (CC). Decreased locomotor activity and motor function and increased anxiety were observed in the hyperthermia groups, and these were more pronounced in the 41°C group. Neuronal survival was significantly decreased in DG, CA1, and CC in the hyperthermia groups (**p < 0.01). Apoptosis was significantly induced in cortex, DG, and CC of the animals exposed to heat (*p < 0.05). In addition, cell proliferation positivity decreased significantly only in DG and CC of the animals exposed to heat (*p < 0.05). Our results suggest that neurobehavioral deficits caused by hyperthermia may be due to the increased apoptosis and neuronal cell death and decreased cell proliferation in the brain of postnatal developing rats.

Polychlorinated biphenyls and organochlorine pesticides in breast milk samples and their correlation with dietary and reproductive factors in lactating mothers in Istanbul.

Persistent organic pollutants (POPs) continue to threaten the environment and human health. We have investigated levels of polychlorinated biphenyls (PCBs) and organochlorinated pesticides (OCPs) in breast milk samples. A questionnaire was also obtained from the study participants. A total of 48 healthy lactating mothers (mean age: 29.5±0.8 years) living in Istanbul volunteered to participate in this study. High-resolution analyses of several OCPs and PCB congeners were done by gas chromatography. The levels of seven major PCB congeners (28, 52, 101, 118, 138, 153, and 180) and eight OCPs (α-benzenehexachloride, ß-benzenehexachloride, δ-benzenehexachloride, hexachlorobenzene (HCB), and 2,4'-dichlorodiphenyldichloroethylene (2,4DDE), 4,4'-dichlorodiphenyldichloroethylene (4,4DDE), 2,4'-dichlorodiphenyltrichloroethane (2,4DDT), and 4,4'-dichlorodiphenyltrichloroethane (4,4DDT)) were determined. The analysis showed that the highest levels of PCBs were observed in PCB 52 (22.99±8.78 ng/g lipid), PCB 101 (12.22±7.8 ng/g lipid), PCB 28 (11.44±5.16 ng/g lipid), and PCB 153 (1.70±0.74 ng/g lipid). The highest OCPs detected were 4,4DDT (3.33±2.05 ng/g lipid) and 4,4DDE (0.86 ± 0.39 ng/g lipid), and the lowest was observed in HCB (0.016 ± 0.01 ng/g lipid). Our findings show that traces of PCBs and OCPs are still present in breast milk of lactating women living in Istanbul, and these pollutants decline in multipara women compared to primipara mothers. We also suggest that breast milk is a useful and representative biological tool for human biomonitoring of POPs.

Comparison of the Effects of Dovitinib and Bevacizumab on Reducing Neovascularization in an Experimental Rat Corneal Neovascularization Model.

PURPOSE: To compare the inhibitory effects of dovitinib and bevacizumab for treatment of corneal neovascularization (CNV). METHODS: Thirty-nine adult female Sprague Dawley rats weighing 180 to 250 g were used. CNV was induced by silver nitrate in the right eye of each rat. After the chemical burn, the animals were randomized into 5 groups. Group 1 did not receive any chemical substance. Group 2 received dimethyl sulfoxide, group 3 received bevacizumab 5 mg/mL, group 4 received dovitinib 5 mg/mL, and group 5 received bevacizumab 5 mg/mL + dovitinib 5 mg/mL topically administered twice daily for 14 days. On the 14th day, slit-lamp examination was performed, and anterior segment photographs were taken. The corneal neovascular area was measured on photographs as the percentage of the cornea's total area using computer imaging analysis. The corneal sections were stained with hematoxylin and eosin for histopathological examination. RESULTS: A statistically significant decrease in the percentage of CNV was found in all treatment groups (group 3, group 4, and group 5) compared with the control group (group 1) (P < 0.01). A statistically significant difference in the percentage of CNV was found among group 3, group 4, and group 5 (P = 0.003). The percentage of CNV in group 4 was significantly higher than that in group 3 and group 5 (P1 = 0.004; P2 = 0.006). There was no statistically significant difference in the percentage of CNV between group 3 and group 5 (P = 0.228). CONCLUSIONS: Dovitinib is a newly developed multitargeted tyrosine kinase inhibitor. Topical administration of dovitinib effectively inhibited CNV, but this effect of dovitinib was found less than topical bevacizumab.

Comparison of the neuroprotective effects of brimonidine tartrate and melatonin on retinal ganglion cells.

PURPOSE: We aimed to compare the neuroprotective effects of brimonidine tartrate (BRT) and melatonin (MEL) on retinal ganglion cells (RGCs) in a rat glaucoma model. METHODS: Thirty-six adult Wistar albino rats were allocated into six groups: control (C), glaucoma (G), BRT, MEL, G + BRT and G + MEL. After establishing the glaucoma model, intraocular pressure (IOP) of all animals measured at day 4 and day 30 was compared statistically with day 0 and day 4, respectively. Prior to sacrification at day 30 for histological evaluation and TUNEL analysis, retrograde labeling of non-apoptotic RGCs with 3% Fluorogold was performed and RGCs were evaluated under fluorescein microscope. RESULTS: IOP measurements at day 4 were significantly higher than basal measurements in all glaucoma groups. BRT alone induced a time-dependent decrease in IOP (p < 0.05), while MEL alone failed to reduce IOP. However, both BRT and MEL reduced IOP in the presence of glaucoma at day 30 (p < 0.05). BRT treatment significantly reversed the reduced non-apoptotic RGC counts (p < 0.01) and increased TUNEL-positive RGCs (p < 0.001) to control group levels in the presence of glaucoma. However, no statistical significance was found between groups G and G + MEL considering 3% Fluorogold-labeled cell counts and apoptotic index values. CONCLUSION: Our study revealed that systemic administration of BRT also has an IOP reducing effect. MEL has no neuroprotective effect on RGCs; on the other hand, BRT acts as a neuroprotective agent against glaucomatous injury, when applied systemically.

Investigation of the effects of kisspeptin-10 in methionine-induced lipid peroxidation in testicle tissue of young rats.

Disruption of the balance oxidants, antioxidants cause various pathophysiological conditions such as lipid peroxidation, protein degradation, or DNA damage. We have examined possible effects of kisspeptin-10 on the structural damage produced by methionine-induced lipid peroxidation in testicle tissue of young rats. Kisspeptin-10 did not significantly affect spermatogenic cells in seminiferous tubules. Testosterone levels decreased in the methionine group as compared with the control group but without statistical significance. Luteinizing hormone levels decreased in the methionine group as compared with the control group (P < 0.001). Catalase enzyme activity increased in the kisspeptin-10 group (P < 0.01) as compared with the other groups. Catalase mRNA expression was decreased in the methionine group as compared with the kisspeptin group (P < 0.001). Total superoxide dismutase enzyme activity and superoxide dismutase mRNA expression were increased in the kisspeptin group as compared with the methionine group (P < 0.05). In conclusion, kisspeptin treatment may protect the structure of spermatogenic cells against methionine-induced damage.

Effects of the gonadotropin-releasing hormone antagonist cetrorelix in the early postimplantation period on rat pregnancy.

OBJECTIVE: The effect of cetrorelix given in the early implantation period on rat pregnancy was investigated. STUDY DESIGN: Forty-nine virgin Sprague-Dawley rats were randomized into six groups. At the 4th or 8th days of sperm plug, groups received 15, 75, 150 µg/kg cetrorelix or saline. Three subjects were randomly selected from each group and sacrificed at 11th gestational day for histomorphometric analysis. The remaining subjects were allowed to complete their pregnancy period. Volumes of total conceptus, labyrinth zone, transitional zone, giant cell zone, and exocoelomic cavity were calculated according to Cavalieri's principle. RESULTS: Subjects receiving cetrorelix at 15 or 150 µg doses at the 4th day (D4) and those receiving cetrorelix at 150 µg dose at the 8th day (D8) of pregnancy delivered later than the controls. On necropsy examination at the 11th day, mean embryo weights of the cetrorelix 15 D4, 150 D4, 15 D8 and 75 D8 groups were found to be significantly lower than that of the controls (p<0.05). On histomorphometric evaluation, volumes of the fetuses and the amniotic sacs were decreased by cetrorelix at all doses studied dose dependently. Gross congenital anomalies were observed in the pups of three rats of the cetrorelix 150 D4 and D8 groups. CONCLUSION: The results of this study suggest that cetrorelix in the early post-implantation period may lead to serious side effects in the rat.