Prenatal immobility stress: Relationship with oxidative stress, inflammation, apoptosis, and intrauterine growth restriction in rats.

BACKGROUND: Prenatal stress is a significant risk factor affecting pregnant women and fetal health. In the present study, we aimed to investigate the effect of immobility stress at different periods of pregnancy on oxidative stress, inflammation, placental apoptosis and intrauterine growth retardation in rats. METHODS: Fifty adult virgin female Wistar albino rats were used. Pregnant rats were exposed to 6 h/day immobilization stress in a wire cage at different stages of pregnancy. Groups I and II (Day 1-10 stress group) were sacrificed on the 10th day of pregnancy, and Group III, Group IV (10-19th-day stress group), and Group V (1-19th-day stress group) were sacrificed on the 19th day of pregnancy. Inflammatory cytokines, including interleukin-6 (IL-6) and interleukin-10 (IL-10), serum corticotropin-releasing hormone (CRH), and corticosterone levels were measured by enzyme-linked immunosorbent assay. Malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) levels in the placenta were spectrophotometrically measured. Histopathological analyses of the placenta were evaluated by hematoxylin and eosin staining. Tumor necrosis factor-alpha (TNF-α) and caspase-3 immunoreactivity in placenta tissues were determined by the indirect immunohistochemical method. Placental apoptosis was determined by the TUNEL staining method. RESULTS: We found that the immobility stress during pregnancy significantly increased serum corticosterone levels. Our results showed that the immobility stress diminished the number and weight of fetuses in rats compared to the non-stress group. The immobility stress caused significant histopathological changes in the connection zone and labyrinth zone and increased placental TNF-α and caspase-3 immunoreactivity and placental apoptosis. In addition, immobility stress significantly increased the levels of pro-inflammatory IL-6 and MDA and caused a significant decrease in the levels of antioxidant enzymes such as SOD, CAT, and anti-inflammatory IL-10. CONCLUSIONS: Our data suggest that immobility stress causes intrauterine growth retardation by activating the hypothalamic-pituitary-adrenal axis and deteriorating placental histomorphology and deregulating inflammatory and oxidative processes.

Toxicological assessment of low-dose bisphenol A, lead and endosulfan combination: chronic toxicity study in male rats.

In the present study, toxic effects, both alone and combined, of bisphenol A (BPA), lead (Pb) and endosulfan (ES) in the low doses were investigated in rat liver and kidney functions. In the study, bisphenol A (BPA), lead (Pb) and endosulfan (ES) were chosen because although they are the chemicals people are most frequently exposed to, no combined toxic effect studies were conducted with these chemicals. Sixty-four male Wistar albino rats were used in the study, and they were randomly divided into eight groups (n = 8 per group); control, BPA (5 mg/kg), Pb (100 ppm), ES (0.61 mg/kg), BPA+Pb, BPA+ES, Pb+ES and BPA+P+ES. The rats were sacrificed after 65 days of treatment. Severe histopathological changes in the liver and kidney tissues were observed in the rats exposed to BPA+Pb+ES combination. Elevated malondialdehyde (MDA) in the liver and decreased superoxide dismutase activity (SOD) in the kidney tissue were detected in the BPA+Pb+ES group compared to those of the control group. It was found that serum alanine aminotransferase (ALT) and blood urea nitrogen (BUN) and creatinine (CREA) levels were higher in the BPA+Pb+ES combination group than the control group. Also, combined exposure of BPA, Pb and ES caused apoptotic cell numbers and inducible nitric oxide (iNOS) to increase in the liver and kidney tissues. The results of the present study suggested that the BPA, Pb and ES caused more dramatic changes to both histological architecture and cell apoptosis in the liver and kidney tissues when there was a combined exposure.

Royal jelly attenuates gastric mucosal injury in a rat ethanol-induced gastric injury model.

The aim of the study was to investigate traditionally used Royal Jelly (RJ) for treating an ethanol-induced gastric ulcer model in rats. A total of 32 Wistar albino male rats were divided into 4 groups of 8: group I = Control, group II = Ethanol, group III = RJ + Ethanol, and group IV = Lansoprazole + Ethanol. In groups II, III, and IV, animals were administered 1 ml of absolute ethanol orally after a 24-h fast to induce ulcer formation. The histopathological changes in the gastric mucosa were determined using hematoxylin-eosin (H&E) staining. Immunohistochemically, inducible nitric oxide (iNOS) and nuclear factor kappa beta (Nf-κß) markings were evaluated in gastric tissue. Cell death in the gastric mucosa was determined by the TUNEL method. Oxidative status markers, superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), and myeloperoxidase (MPO) levels were determined spectrophotometrically. Expression of the interleukin - 1 beta (IL-1ß) and tumor necrosis factor-α (TNF-α) genes in gastric tissues was determined by real-time PCR; and TNF-α, IL-10, and IL-1ß levels were determined. RJ was found to inhibit iNOS and Nf-κß activity in the gastric mucosa and prevent epithelial cell apoptosis. In particular, pro-inflammatory cytokines TNF-α and IL-1ß levels were significantly decreased in the RJ + Ethanol group compared to the Ethanol group. In addition, a decrease in the MPO level indicated that RJ prevented tissue damage, especially by preventing inflammatory cell infiltration. The study demonstrated a possible gastroprotective effect of RJ in a rat ethanol-induced gastric ulcer model.

Protective Effect of Nigella Sativa on Renal Reperfusion Injury in Rat.

INTRODUCTION: This study was designed to investigate the effect of Nigella sativa (NS), in reperfusion-induced renal injury in rats. MATERIALS AND METHODS: A total of 24 male Sprague-Dawley rats were divided into 3 groups of controls and rats that underwent ischemia-reperfusion with and without pretreatment with NS. A rat model of renal reperfusion injury was induced by 45-minute occlusion of the bilateral renal pedicles and 24-hour reperfusion. In the NS group, a single dose NS (400 mg/kg orally) was administered by gastric gavage. RESULTS: Renal reperfusion caused severe histopathological injury such as tubular damage, atrophy dilatation, loss of brush border, and hydropic epithelial cell degenerations. Treatment with NS significantly attenuated the severity of reperfusion injury and significantly lowered tubulointerstitial damage score as compared with the reperfusion group. When kidney sections were stained with anti-proliferating-cell nuclear antigen antibody, nuclear factor kappaB p65 antibody, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, there was a clear increase in the number of positive cells in the reperfusion group in the renal cortical tissues. However, there was a significant reduction in the number of stain-positive cells in kidney tissue from the NS group. Treatment of renal reperfusion injury with NS decreased the elevated tissue malondialdehyde levels and increased the reduced activities of the enzymatic antioxidants glutathione peroxidase and catalase. CONCLUSIONS: Pretreatment with NS has a protective effect against renal damage induced by renal reperfusion. This protective effect is possibly due to its ability to inhibit reperfusion-induced renal damage, apoptosis, and cell proliferation.

Quercetin ameliorates methotrexate-induced renal damage, apoptosis and oxidative stress in rats.

BACKGROUND: In the present study, the protective and therapeutic effects of quercetin (QE) on renal injury induced by methotrexate (MTX) have been examined. MATERIALS AND METHODS: A total of 24 male rats were divided into the following three groups: control group, MTX group, and MTX + QE group. Rats in MTX group received 20 mg/kg of single dose of MTX, while those in MTX + QE group received 20 mg/kg of single dose MTX, in addition to 15 mg/kg of QE administered 30 min prior to MTX and in the following 5-day period as a single daily dose. At the end of the experimental period, renal tissues were removed for histopathological and biochemical assessments. RESULTS: Light microscopic examination showed a disruption of the renal structure in rats in MTX group in the form of tubular degeneration and dilation, with shedding of the tubular epithelial cells into the lumen. QE treatment was associated with less marked degenerative changes, with a similar histological appearance to that of controls. Furthermore, QE treatment resulted in decreased the number of apoptotic cells. Biochemical assessments showed significantly higher malondialdehyde (MDA) levels in MTX group as compared to control and MTX + QE groups. superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) levels showed a significant decrease in MTX group as compared to controls. However, QE significantly suppressed MDA level, compensated deficits in the anti-oxidant defenses [reduced SOD, GSH-Px, and CAT levels] in kidney tissue resulted from MTX administration. CONCLUSIONS: In conclusion, renal toxic effects of MTX may be alleviated by QE.