Effects of prenatal PPAR-γ agonist rosiglitazone exposure on rat hippocampus development in a time-dependent manner: A stereological and histopathological study.

Rosiglitazone is in the thiazolidinedione class of drugs used in the treatment of type 2 diabetes mellitus. It works as an insulin sensitizer by binding to the peroxisome proliferator-activated receptor gamma. We investigated the effects of prenatally administered rosiglitazone on pyramidal cell numbers and morphologies in the hippocampus at postnatal period using histochemical and stereological techniques, congenital morphological properties and the number of offspring in rats. Eighteen female rats were grouped into control (C), low-dose rosiglitazone (LDR) and high-dose rosiglitazone (HDR). LDR pregnant rats received 2 mg/kg/day of rosiglitazone via oral gavage during the first 16 days of the pregnancy. HDR rats received 5 mg/kg/day. The infants were grouped into newborn (NB), 4 week (4 W) and 12 week (12 W). A side from histopathologic and congenital assessments, stereological analyses were performed using the optical fractionator method. Congenital anomaly was not detected in any of the rosiglitazone treatment groups, and their number of offspring was similar to that of the C group. Stereological counts revealed a significant reduction in the number of hippocampal pyramidal cells in the C and LDR groups but not in the HDR group until birth to 12th week. When NB groups were compared, the number of pyramidal cells in the HDRNB group was less than those in the LDRNB and CNB groups. HDR affected apoptosis or the proliferation and maturation of progenitor cells to the pyramidal neuron during neurodevelopment in the hippocampus, whereas LDR did not adversely affect neuronal development and did not cause congenital anomalies.

The value of Nigella sativa in the treatment of experimentally induced rhinosinusitis.

The aim of this study was to investigate the effect of Nigella sativa and cephalexin in the therapy of experimental bacterial rhinosinusitis. Bacterial rhinosinusitis was induced with Staphylococcus aureus. Rabbits were divided into five groups; control (n = 6), N. sativa 50 mg/ kg/d (n = 6), N. sativa 100 mg/kg/d (n = 6), N. sativa 200 mg/kg/d (n = 6), and cephalexin 20 mg/kg/d (n = 6) groups. N. sativa was given orally for 7 days. The same volume of normal saline (0.9% NaCl) was given as a vehicle to the control group for the same period. After treatment period, sinus mucosa samples were evaluated using stereological and histopathological methods. Half of the maxillary sinus mucosa samples were frozen at -800C for further analysis of NO levels. Pathology revealed a severe acute inflammatory process in rabbits treated with saline. Only mild inflammation was determined in cephalexin group, N. sativa 100 mg/kg/d and N. sativa 200 mg/kg/d groups. The level of NO increased in the saline group was significantly reduced in all treatment groups. N. sativa may prevent histopathological changes of rhinosinusitis via decreased NO levels in a dose dependent manner and can be used in the treatment of rhinosinusitis diseases.

Blockade of endothelin receptors with bosentan limits ischaemia/reperfusion-induced injury in rat ovaries.

OBJECTIVE: To investigate the role of endothelin receptors in ovarian ischaemia/reperfusion (I/R) injury in rats using the endothelin receptor antagonist bosentan. STUDY DESIGN: Group 1: sham operation; Group 2: sham operation and bosentan 60 mg/kg; Group 3: bilateral ovarian ischaemia; Group 4: 3-h period of ischaemia followed by 3h of reperfusion; Groups 5 and 6: bosentan 30 and 60 mg/kg, respectively, with bilateral ovarian ischaemia applied 30 min later; the bilateral ovaries were removed after 3h of ischaemia; Groups 7 and 8: 3h of bilateral ovarian ischaemia was applied, with bosentan 30 and 60 mg/kg, respectively, administered 2.5h after the induction of ischaemia; following the 3-h period of ischaemia, 3h of reperfusion was applied, after which the ovaries were removed. RESULTS: Ischaemia and I/R decreased superoxide dismutase (SOD) activity and the level of glutathione (GSH) in ovarian tissue, but increased the level of malondialdehyde (MDA) significantly compared with the sham operation group. Bosentan 30 and 60 mg/kg before ischaemia and I/R decreased the MDA level and increased SOD activity and the GSH level in the experimental groups. The serum levels of the inflammatory cytokines interleukin (IL)-1ß, IL-6 and tumour necrosis factor-α were also measured in the I/R injury model in rat ovaries. The levels of these cytokines were significantly higher in the ischaemia and I/R groups compared with the sham operation and sham operation plus bosentan groups. The histopathological findings also demonstrated the protective role of bosentan against I/R-induced injury in rat ovaries. CONCLUSION: Administration of bosentan protects the ovaries against oxidative damage and I/R-induced injury.

Effects of diabetes and ovariectomy on rat hippocampus (a biochemical and stereological study).

Oxidative stress is one of the main reasons of both menopause and diabetes. So, it plays crucial role in the pathogeneses of that condition and disease. Therefore, the objective of the present study was to investigate the effects of menopause and diabetes upon the hippocampus using a rat model. Adult female Sprague Dawley rats (n = 24) were allocated randomly as follows; control (C group) ovariectomized (O group), diabetic (D group) and ovariectomy plus diabetic groups (DO group) (n = 6; in each group), respectively. For evaluating the results, tissue biochemistry and stereological analysis were made. Biochemistry results (lipid peroxidase (LPO); catalase (CAT); superoxide dismutase (SOD); total glutatyon (GSH); and myeloperoxidase (MPO) values) in Group C-DO were determined as 12.27, 21.88, 23.08 and 29.90 nmol/gr tissue; 59.3, 70.06, 69.7 and 78.1 mmol/min/mg tissue; 174.2, 156.4, 159.7 and 154.6 mmol/min/mg tissue; 3.63, 3.61, 4.21 and 3.97 nmol/mg tissue; and 5.05, 5.68, 5.58 and 6.19 µmol/min/mg tissue, respectively. Moreover, both menopause and diabetes led to change of lipid profiles. There were significant differences between the control and other groups (Group C and D-DO) (p < 0.01) and among experimental groups (p < 0.01) in terms of neuron number. When the volumes of the hippocampus were compared, there were no significant differences between the all groups (P > 0.05). At this point, we suggested that diabetes could aggravate deleterious effects of ovariectomy.