Dose-dependent effects of prenatal exposure of pioglitazone, the PPARγ agonist, on the hippocampus development and learning and memory performance of rat offspring.

It is known that pioglitazone, defined as a PPARγ agonist, has neuron-protective properties in nervous system disorders. The aim of this study is to investigate the effects of pioglitazone administration at different doses during prenatal period on the neurons, glial cells and learning-memory levels in the hippocampus of rat offspring. Pregnant rats were divided into three groups; Low-Dose Pioglitazone (LDP), High-Dose Pioglitazone (HDP) and control (C) (n = 3). Pregnant rats in the HDP and LDP groups were given pioglitazone at 30 mg/kg and 5 mg/kg doses, respectively, by gavage once a day during their pregnancy. No procedure was applied to the rats in the control group. Morris water tank test was applied to offspring obtained from postnatal 24th to 28th day. The offspring were sacrificed on the 29th postal day and their brain tissues removed. Stereological, histopathological and immunohistochemical techniques were used to analyze brain tissues. As a result of the analysis, it was observed that there were delays in learning and memory, the number of pyramidal neurons decreased, and the density of cells stained with glial fibrillar acidic protein (GFAP) positive increased in the HDP group compared to the other groups (p < 0.05). No significant difference was found between the LDP and control groups in terms of these parameters (p > 0.05). Our results showed that pioglitazone administered in the prenatal period had an effect on the hippocampus development and learning and memory performance of rats, depending on the dose.

A histopathological and stereological study of the effects of acetylsalicylic acid on doxorubicin-induced hepatotoxicity in mice.

Doxorubicin (Dox) is an anthracycline antibiotic with antineoplastic activity. Acetylsalicylic acid (Asa) is recommended for use as a prophylactic for thromboembolism during treatment of cancers. We investigated liver toxicity due to combined use of Dox and Asa in chemotherapy regimens. We used 140 Swiss albino mice divided into four main groups: control, Dox, Asa, and Dox + Asa. Each group was subdivided into seven subgroups based on time of sacrifice, i.e., 6, 12, 24, 48 h and 7, 14, 21 days. Quantitative and histopathological changes in liver were assessed by light microscopy and stereology. The portal triad area of the Dox and Dox + Asa groups was increased significantly compared to controls at 6 h, whereas in the Asa group, the means were similar to controls. Assessment of histopathology indicated an increased time-dependent degeneration and necrosis of liver tissues in mice in the Dox and Dox + Asa groups. The protective effects of Asa were not evident in Dox + Asa group. When Dox and Asa were administered together, degenerative changes were greater than for in the group that was given Dox alone. We found that Asa and Dox combined therapy increased tissue damage.

Protective effects of curcumin and Ganoderma lucidum on hippocampal damage caused by the organophosphate insecticide chlorpyrifos in the developing rat brain: Stereological, histopathological and immunohistochemical study.

The aim of this study is to draw attention to the possible effects of chlorpyrifos exposure on the developing rat hippocampus in the prenatal period and to determine whether these effects can be reduced with various antioxidant substances. Pregnant rats were divided into 7 groups.; Chlorpyrifos (CPF), Curcumin (CUR), Ganoderma lucidum (GNL), Chlorpyrifos + Curcumin (CPF + CUR), Chlorpyrifos + Ganoderma lucidum, (CPF + GNL), SHAM and Control (C). After the experiments, brain tissues were evaluated by stereological and immunohistochemical methods. As a result of the stereological analyzes, it was determined that the number of pyramidal neurons in the hippocampus of the CPF group decreased significantly from all other groups. In contrast, the number of neurons in the CPF + CUR and CPF + GNL groups was significantly higher than the CPF group. In addition, immunohistochemical analyzes showed that the density of cells stained with glial fibrillar acidic protein (GFAP) positive in all areas in the hippocampus of the rats in the CPF group was significantly higher compared to the control group, whereas in the CPF + CUR and CPF + GNL groups were less than the CPF group. As a result, the exposure of CPF in the prenatal period caused neurotoxicity in the brain hippocampus, whereas CUR and GNL reduced this toxicity caused by CPF.

Inhibition of acrolein-induced apoptosis by the antioxidant selenium.

In this study, the effects of a potent antioxidant, selenium, on apoptosis induced by acrolein, a cytotoxic and genotoxic environmental pollutant, were investigated by immunohistochemical and electron microscopic methods. One hundred adult male Wistar albino rats were used in the study. The rats were divided into four main groups: control, acrolein, selenium, and acrolein + selenium. The animals in the experimental groups were given 1 mg/kg/day selenium and 4 mg/kg/day acrolein daily for 7 days by gavage. After drug administration, each group was divided into subgroups according to the time they were to be euthanized: 12th hour, 1st, 2nd, 3rd, and 5th day. The rats in each group at the determined time were euthanized and their livers were removed. Routine histological procedures were performed for light and electron microscopy examinations. After applying the Terminal Deoxynucleotidyl Transferase dUTP nick end labeling assay on the liver sections, apoptotic index values were calculated. Comparing the liver sections of the rats in the acrolein group and the control group, acrolein was found to cause a significant increase in the apoptotic index. The apoptotic index values of the acrolein + selenium group decreased compared to the acrolein group. In the electron microscopic examinations, apoptotic findings were observed in the liver tissues of the rats given acrolein, such as chromatin condensation in the nucleus of hepatocytes, dilatations in the perinuclear space, and cytoplasmic vacuolization. These apoptotic findings were not observed in the acrolein + selenium group after the 12th hour. These findings show that selenium may potentially be useful as a protective agent for people exposed to acrolein.

Efficacy of Extracorporeal Shockwaves Therapy on Peripheral Nerve Regeneration.

PURPOSE: This study was conducted to determine the effects of different doses and methods of extracorporeal shock wave treatment (ESWT) on the sciatic nerve regeneration of rat model using unbiased quantitative stereological techniques and to know which method and dose were effective. METHODS: Twenty-five Wistar albino rats were used in the experiment. All animals were randomly divided into 5 groups. To the first group (control, n = 5) ESWT and surgery were not applied. To 2nd group (E300*2, n = 5), twice doses of 300 impulses uESWs (unfocused) were applied. To 3rd group (E500*2, n = 5), twice doses of 500 impulses uESWs (unfocused) were applied. To 4th group (E300*2, n = 5), twice doses of 300 impulses of fESWs (focused) were applied. To 5th group (E500*2, n = 5), twice doses of 500 impulses of fESWs (focused) were applied. Rats were sacrificed and nerve samples analyzed on the 22nd day following the operation. RESULTS: There is a variable increase in the axon numbers among the shockwave treated groups in compare to the control group. The focused groups showed better improvement and the 300-focused group has shown the highest regeneration rate. CONCLUSION: The authors found that ESWT promotes nerve regeneration, increases the thickness of the myelin sheath and that the most effective result is in the 300 shock wave.

Stereological examination of curcumin's effects on hippocampal damage caused by the anti-epileptic drugs phenobarbital and valproic acid in the developing rat brain.

The anti-epileptic drugs phenobarbital and valproic acid have an extremely strong negative effect on cognitive processes such as learning and memory in the developing brain. We examined whether or not curcumin has protective effects on neuronal injury caused by these drugs in the developing rat brain. Young male Wistar rats were studied in two groups, a 7 days old and a 14 days old group (35 rats in each). Both groups were then divided into 7 sub-groups as the control, curcumin, dimethylsulfoxide, phenobarbital, valproic acid, phenobarbital + curcumin, and valproic acid + curcumin groups (n = 5 in each group). At 24 h after the intraperitoneal injection of the compounds, the rats were sacrificed, and the hippocampal tissue was subjected to stereological analysis with the optical fractionation method. Total numbers of neurons in the hippocampus of the 7 days old and 14 days old rats were calculated. It was found that treatment with phenobarbital resulted in a loss of 43% of the neurons, and valproic acid induced a loss of 57% of the neurons in the 7 days old rats. Curcumin prevented this loss significantly with only 19% in the phenobarbital group and 41% in the valproic acid group. In the 14 days old rat groups, phenobarbital was found to reduce the number of neurons by 30%, and valproic acid reduced it by 38%. Curcumin treatment limited neuronal loss to 3% in the phenobarbital + curcumin group and 10% in the valproic acid + curcumin group. These data strongly indicate that curcumin is a protective agent and prevents hippocampal neuronal damage induced by phenobarbital and valproic acid treatment.