Do small for gestational age fetuses have placental pathologies?

PURPOSE: Although small for gestational age (SGA) does not cause adverse perinatal outcomes, the placental pathology for fetal growth restricted (FGR) and SGA fetuses is still unknown. The aim of this study is to evaluate the differences between placentas of early onset FGR, late onset FGR, SGA, and appropriate for gestational age (AGA) pregnancies in the manner of microvasculature and expression of anti-angiogenic PEDF factor and CD68. METHODS: The study included four groups (early onset FGR, late onset FGR, SGA and AGA). Placental samples were obtained just after labor in all of the groups. Degenerative criteria were investigated with Hematoxylin-eosin staining. Immunohistochemical evaluation with H score and m RNA levels of Cluster of differentiation 68 (CD68) and pigment epithelium derived factor (PEDF) were performed for each group. RESULTS: The highest levels of degeneration were detected in the early onset FGR group. In means of degeneration SGA placentas were found to be worse than the AGA placentas. The intensity of PEDF and CD68 were significant in early FGR, the late FGR and SGA groups compared to the AGA group (p < 0.001). The mRNA level results of the PEDF and CD68 were also parallel to the immunostaining results. CONCLUSION: Although SGA fetuses are considered constitutionally small, the SGA placentas also demonstrated signs of degeneration similar to the FGR placentas. These degenerative signs were not seen among the AGA placentas.

Boric Acid Alleviates Gastric Ulcer by Regulating Oxidative Stress and Inflammation-Related Multiple Signaling Pathways.

Oxidative stress and inflammation have pivotal roles in gastric ulcer development caused by alcohol consumption. Trace element boric acid taken into the human and animal body from dietary sources displays strong antioxidant and anti-inflammatory functions. However, the mechanisms underlying these actions of boric acid remain unclear, and its effectiveness in preventing gastric lesions is unknown. Therefore, the present study was undertaken to evaluate the protective effects of boric acid in alcohol-induced gastric ulcer and elucidate its potential mechanisms. Gastric ulcer was induced by 75% oral ethanol administration in rats, and the effectiveness of prophylactic boric acid treatment at 100 mg/kg concentration was assessed by histopathological examination, ELISA assay and qRT-PCR. Gross macroscopic and histopathological evaluations revealed that boric acid alleviated gastric mucosal lesions. Boric acid decreased reactive oxygen species (ROS) and malondialdehyde (MDA) concentration and the overall oxidation state of the body while improving antioxidant status. It reduced the concentration of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). The mRNA expression of JAK2 and STAT3 was decreased while the expression of AMPK was increased with boric acid pretreatment. Moreover, Sema3A and PlexinA1 levels were elevated upon boric acid pretreatment, and homocysteine levels were reduced. Our results demonstrated that boric acid protects gastric mucosa from ethanol-induced damage by regulating oxidative and inflammatory responses. In addition, our findings suggested that the gastroprotective activity of boric acid could be attributed to its regulatory function in the IL-6/JAK2/STAT3 signaling modulated by AMPK and that Sema3A/PlxnA1 axis and homocysteine are potentially involved in this process.

Ex vivo investigation of betaine and boric acid function as preprotective agents on rat synaptosomes to be treated with Aß (1-42).

Recent evidence suggests that ferroptosis, an iron-dependent cell death process, may be involved in Alzheimer's disease (AD) pathology. The study evaluated the therapeutic potential of betaine and boric acid (BA) pretreatment administered to rats for 21 days in AD. Then, the rats were sacrificed, and morphological and biochemical analyses were performed in brain tissues. Next, an ex vivo AD model was created by applying amyloid-ß (Aß1-42) to synaptosomes isolated from the brain tissues. Synaptosomes were analyzed with micrograph images, and protein and mRNA levels of ferroptotic markers were determined. Betaine and BA pretreatments did not cause any morphological and biochemical differences in the brain tissue. However, Aß (1-42) administration in synaptosomes increased the levels of acyl-CoA synthetase long chain family member-4 (ACSL4), transferrin receptor-1 protein (TfR1), malondialdehyde (MDA), and 8-hydroxydeoxyguanosine (8-OHdG) and decreased the levels glutathione peroxidase-4 (GPx4) and glutathione (GSH). Moreover, ACSL4, GPx4, and TfR1 mRNA and protein levels were similar to the ELISA results. In contrast, betaine and BA pretreatments decreased the levels of ACSL4, TfR1, MDA, and 8-OHdG in synaptosomes incubated with Aß1-42, while promoting increased levels of GPx4 and GSH. In addition, betaine and BA pretreatments completely reversed ACSL4, GPx4, and TfR1 mRNA and protein levels. Therefore, betaine and BA pretreatments may contribute to the prevention of neurodegenerative damage by supporting antiferroptotic activities.

An Investigation into the Protective Effects of Various Doses of Boric Acid on Liver, Kidney, and Brain Tissue Damage Caused by High Levels of Acute Alcohol Consumption.

Acute high-dose alcohol consumption can lead to oxidative stress, which can cause harm to organs. In this study we aim to determine whether administering boric acid (BA) can protect certain organs (liver, kidney, and brain) from the damaging effects of alcohol by reducing oxidative stress. We used 50 and 100 mg/kg of BA. Thirty-two Sprague Dawley (12-14-week-old) male rats in our study were separated into four groups (n=8); control, ethanol, ethanol+50 mg/kg BA, and ethanol+100 mg/kg BA groups. Acute ethanol was given to rats by gavage at 8 g/kg. BA doses were given by gavage 30 min before ethanol administration. Alanine transaminase (ALT) and aspartate transaminase (AST) measurements were made in blood samples. The total antioxidant status (TAS), total oxidant status (TOS), OSI (oxidative stress index) (TOS/TAS), malondialdehyde (MDA) levels and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities were measured to determine the oxidative stress induced by high-dose acute ethanol in the liver, kidney, and brain tissue, and the antioxidant effects of BA doses. According to our biochemical results, acute high-dose ethanol increases oxidative stress in liver, kidney, and brain tissues, while BA reduces the damage in tissues with its antioxidant effect. For the histopathological examinations, hematoxylin-eosin staining was performed. As a result, we found that the effect of alcohol-induced oxidative stress on liver, kidney, and brain tissues was different, and that giving boric acid reduces the increased oxidative stress in tissues due to its antioxidant effect. It was found that 100mg/kg BA administration had a higher antioxidant effect than in the 50mg/kg group.

Resveratrol downregulates ENaCs through the activation of AMPK in human colon cancer cells.

Epithelial sodium channels (ENaCs) are critically engaged in a number of hallmarks of cancer progression, including proliferation, migration, invasion and apoptosis. Thus, the inhibition of ENaCs possesses therapeutic potential in cancer. Resveratrol, a natural polyphenol with anti-carcinogenic activity, is a potent activator of 5' AMP-activated protein kinase (AMPK) which reduces the abundance of ENaCs in the cell membrane by causing the internalization of the ß subunit. However, the effect of resveratrol on ENaCs in cancer cells is unknown. Therefore, in this study, we aimed to investigate the effects of resveratrol on ENaCs in human colon cancer cells HCT116 and HT29. The influences of resveratrol either alone or together with AMPK inhibitor compound C (CC), and ENaC inhibitor amiloride on cell viability were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression levels of phospho-AMPK Thr172 and ßENaC in cells were determined by immunofluorescence staining, and the expression of apoptotic markers Caspase-3 and Caspase-9 were analyzed by qRT-PCR. Resveratrol was found to activate AMPK in a dose-dependent manner. Both AMPK activation by resveratrol and ENaC inhibition by amiloride decreased cell viability and increased apoptosis significantly. AMPK activation also reduced ßENaC expression in cells. Our results suggest that ENaC inhibition through AMPK activation might be a potential mechanism underlying the anti-cancer effects of resveratrol.

Protective effect of cerium oxide on testicular function and oxidative stress after torsion/detorsion in adult male rats.

Testicular torsion (T)/detorsion (D) can cause testicular injury due to the rotation of the spermatic cord and its vessels, therefore it represents an urological emergency that is surgically treated. Oxidative damage occurs in the testis and distant organs because of the overproduction of free radicals and overexpression of proinflammatory cytokines by reperfusion after surgery. Cerium oxide (CeO2) nanoparticles, a material also known as nanoceria, have regenerative antioxidant properties on oxidative stress. The present study aimed to investigate the effects of nanoceria on testis tissues in testicular T/D in rats. A total of 24 rats were equally and randomly divided into four groups: Control, CeO2, T/D and CeO2-T/D groups. Left inguinoscrotal incision was performed in the control group. In the CeO2 group, 0.5 mg/kg CeO2 was given intraperitoneally 30 min before inguinoscrotal incision. In the T/D group, unilateral testicular T/D was performed through an inguinoscrotal incision and rotating the left testis 720˚ clockwise, which was then left ischemic for 120 min, followed by 120 min of reperfusion. In the CeO2-T/D group, 0.5 mg/kg CeO2 was given intraperitoneally 30 min before testicular T/D. At the end of the experiment, testis tissues were removed for histopathological and biochemical examinations. The samples were histologically examined, Glutathione-s transferase (GST), catalase (CAT), paraoxonase (PON) activities and malondialdehyde (MDA) levels were measured via biochemical analysis methods, while the expression levels of p53, Bax and Bcl-2 were detected using immunohistochemistry. The present results revealed statistically significant inter-group differences in PON, CAT and GST activities and MDA levels. GST, CAT and PON activities were significantly higher, whereas MDA levels in the CeO2-T/D group were significantly lower compared with those in the T/D group. The T/D group had increased Bax and decreased Bcl-2 expression levels in their seminiferous tubules compared with the control and CeO2 groups. CeO2 treatment led to downregulation of Bax and upregulation of Bcl-2. The expression of p53 was high in the T/D group compared with that in the control and CeO2 groups, and was upregulated in all germinal cells. However, compared with that in the T/D group, p53 expression was significantly decreased in the CeO2-T/D group. The testicular injury score significantly increased in the CeO2-T/D group compared with the control and CeO2 groups. Rats in the CeO2-T/D group demonstrated significantly milder tissue lesions compared with those in T/D group. The present findings indicated that nanoceria may protect testis in rats against the harmful effects of T/D. Further studies are required to evaluate how CeO2 reduces oxidative stress and cell death in testis tissue that underwent T/D-related injury.

Can Quercetin be an Option for Treatment of Spinal Cord Injury? An Experimental Study.

AIM: To determine the neuroprotective functions of quercetin and compare them with methylprednisolone in an experimental spinal cord injury model in rats. MATERIAL AND METHODS: Thirty male, Wistar rats were assigned to five experimental groups: sham (n=6), trauma (n=6), methylprednisolone (n=6), single dose quercetin (n=6), and multiple doses of quercetin (n=6). An aneurysm clip compression method was used to produce spinal cord injury at level T7-9 after performing a laminectomy. In the sham group, only a laminectomy was performed. Clip compression was performed to the spinal cord after laminectomy in the trauma group. For Group 3, a single dose of intraperitoneal (ip) methylprednisolone (30mg/kg) was administered after laminectomy and trauma. A single dose of ip quercet in (100mg/kg) was administered after laminectomy and trauma in Group 4. For Group 5, multiple doses of ip quercetin (100 mg/kg) were administered on the first, second, and third days after laminectomy and trauma. Spinal cord and serum samples were obtained to measure the levels of malondialdehyde (MDA), nitric oxide (NO), total antioxidant levels (TAL) at the 72nd hour. Neurofunctional examinations of all the rats according to Drummond and Moore criteria and inclined-plane tests to evaluate functional healing were performed. All rats were sacrificed via intracardiac blood depletion after the procedure. RESULTS: Quercetin and methylprednisolone both increased plasma and tissue levels of NO and MDA, and decreased TAL, with a statistically significant difference (p < 0.05). NO and MDA levels in plasma and tissue were significantly higher in the trauma group (Group 2) when compared to the sham group (Group 1), and TAL levels were significantly lower (p < 0.05). There was a statistically significant increase in the treatment group's inclined-plane test (p < 0.05), while there was no difference in motor examination evaluations. CONCLUSION: The results of this experimental study suggest that quercetin can be thought as an option of treatment in spinal cord injury.