Corrigendum: TSG-6 Inhibits Oxidative Stress and Induces M2 Polarization of Hepatic Macrophages in Mice With Alcoholic Hepatitis via Suppression of STAT3 Activation.

[This corrects the article DOI: 10.3389/fphar.2020.00010.].

TSG-6 Inhibits Oxidative Stress and Induces M2 Polarization of Hepatic Macrophages in Mice With Alcoholic Hepatitis via Suppression of STAT3 Activation.

Tumor necrosis factor (TNF)-α-stimulated protein 6 (TSG-6) is a secreted protein with diverse tissue protective and anti-inflammatory properties. We aimed to investigate its effective in treating mice with alcoholic hepatitis (AH) and the associated mechanisms. AH was induced in 8-10 week female C57BL/6N mice by chronic-binge ethanol feeding for 10 days. Intraperitoneal (i.p.) injection of recombinant mouse TSG-6 or saline were performed in mice on day 10. Blood samples and hepatic tissues were collected on day 11. Biochemistry, liver histology, flow cytometry, and cytokine measurements were conducted. Compared to the normal control mice, the AH mice had significantly increased liver/body weight ratio, serum alanine aminotransferase (ALT) and aspartate aminotransferases (AST), hepatic total cholesterol (TC), triglyceride (TG), malondialdehyde (MDA), hepatic macrophage infiltration, serum and hepatic interleukin (IL)-6, and tumor necrosis factor (TNF)-α, which were markedly reduced by i.p. injection of rmTSG-6. Compared to the normal control mice, the hepatic glutathione (GSH), accumulation of M2 macrophages, serum, and hepatic IL-10 and TSG-6 were prominently reduced in the AH mice, which were significantly enhanced after i.p. injection of rmTSG-6. Compared to the normal control mice, hepatic activation of signal transducer and activator of transcription 3 (STAT3) was significantly induced, which was markedly suppressed by rmTSG-6 treatment. TSG-6 were effective for the treatment of AH mice, which might be associated with its ability in inhibiting hepatic oxidative stress and inducing hepatic M2 macrophages polarization via suppressing STAT3 activation.

Mesenchymal stem cells reduce alcoholic hepatitis in mice via suppression of hepatic neutrophil and macrophage infiltration, and of oxidative stress.

Mesenchymal stem cells (MSCs) are a population of pluripotent cells that have been tested for the treatment of many inflammatory diseases. It remains unclear whether MSCs were effective in treating mice with alcoholic hepatitis (AH) and its underlying mechanism. In the present study, MSCs were isolated from bone marrow of 4-6 week-old C57BL/6N male mice. AH was induced in female mice by chronic-binge ethanol feeding for 10 days. Intraperitoneal (i.p.) transplantation of MSCs or saline were performed in mice on day 10. Blood samples and hepatic tissues were harvested on day 11. Biochemical, liver histological and flow cytometric analyses were performed. Compared to the control mice, the AH mice had significantly increased liver/body weight ratio, serum alanine aminotransferase (ALT) and aspartate aminotransferases (AST), hepatic total cholesterol (TC), triglyceride (TG), malondialdehyde (MDA), hepatic neutrophil and macrophage infiltration (P<0.001), which were markedly reduced by i.p. transplantation of MSCs (P<0.01). Compared to the control mice, the hepatic glutathione (GSH) was prominently lower in the AH mice (P<0.001), which was markedly enhanced after i.p. injection of MSCs (P<0.001). MSCs were effective for the treatment of AH mice, which might be associated with their ability in inhibiting hepatic neutrophil and macrophage infiltration, and alleviating oxidative stress.

Mesenchymal stem cells alleviate liver injury induced by chronic-binge ethanol feeding in mice via release of TSG6 and suppression of STAT3 activation.

BACKGROUND: Mesenchymal stem cells (MSCs) are a population of pluripotent cells that might be used for treatment of liver disease. However, the efficacy of MSCs for mice with alcoholic hepatitis (AH) and its underlying mechanism remains unclear. METHODS: MSCs were isolated from the bone marrow (BM) of 4-6-week-old male C57BL/6 N mice. AH was induced in female mice by chronic-binge ethanol feeding for 10 days. The mice were given intraperitoneal injections of MSCs with or without transfection or AG490, recombinant mouse tumor necrosis factor (TNF)-α-stimulated gene/protein 6 (rmTSG-6), or saline at day 10. Blood samples and hepatic tissues were collected at day 11. Various assays such as biochemistry, histology, and flow cytometry were performed. RESULTS: MSCs reduced AH in mice, decreasing liver/body weight ratio, liver injury, blood and hepatic lipids, malondialdehyde, interleukin (IL)-6, and TNF-ɑ, but increasing glutathione, IL-10, and TSG-6, compared to control mice. Few MSCs engrafted into the inflamed liver. Knockdown of TSG-6 in MSCs significantly attenuated their effects, and injection of rmTSG-6 achieved similar effects to MSCs. The signal transducer and activator of transcription 3 (STAT3) was activated in mice with AH, and MSCs and rmTSG-6 inhibited the STAT3 activation. Injection of MSCs plus AG490 obtained more alleviation of liver injury than MSCs alone. CONCLUSIONS: BM-MSCs injected into mice with AH do not engraft the liver, but they secrete TSG-6 to reduce liver injury and to inhibit STAT3 activation.

Testing of behavioral and cognitive development in rats after prenatal exposure to 1800 and 2400 MHz radiofrequency fields.

The objective of the study was to explore the effects of behavioral and cognitive development in rats after prenatal exposure to 1800 and 2400 MHz radiofrequency fields. Pregnant female rats were exposed to radiofrequency fields beginning on the 21st day of pregnancy. The indicators of physiological and behavioral development were observed and measured in the offspring rats: Y maze measured at 3-weeks postnatal, open field at 7-weeks postnatal, and the expression of N-methyl-D-aspartate receptors (NMDARs) measured by reverse transcription-PCR in the hippocampus at 9-weeks postnatal. The body weight of the 1800 MHz group and the 1800 MHz + WiFi group showed a downward trend. The eye opening time of newborn rats was much earlier in the WiFi group than in the control group. Compared to the control group, the overall path length of the 1800 MHz + WiFi group was shortened and the stationary time was delayed. The path length of the WiFi group was shortened and the average velocity was increased in the error arm. The 1800 MHz + WiFi group displayed an increased trend in path length, duration, entry times and stationary time in the central area. In both the 1800 MHz + WiFi and WiFi groups, NR2A and NR2B expression was down-regulated, while NR2D, NR3A and NR3B were up-regulated. Moreover, NR1 and NR2C in the WiFi group were also up-regulated. Prenatal exposure to 1800 MHz and WiFi radiofrequency may affect the behavioral and cognitive development of offspring rats, which may be associated with altered mRNA expression of NMDARs in the hippocampus.

The Effect of Transjugular Intrahepatic Portosystemic Shunt Plus Partial Splenic Embolization for the Treatment of Patients with Recurrent Variceal Bleeding.

RATIONALE AND OBJECTIVES: Transjugular intrahepatic portosystemic shunt (TIPS) and partial splenic embolization (PSE) were two interventional therapies effective for the management of variceal bleeding with cirrhosis. This study aimed to investigate the effect of TIPS plus PSE for the treatment of patients with cirrhosis and recurrent variceal bleeding. MATERIAL AND METHODS: This is a single-center, nonrandomized and retrospective study that included 32 patients undergoing TIPS alone (the TIPS group) and 16 patients undergoing TIPS plus PSE (the TIPS+PSE group). RESULTS: The 5-year cumulative rates of variceal rebleeding (20.0% vs. 37.9%, p = 0.027) and shunt stenosis (35.1% vs. 55.9%, p = 0.036) in the TIPS+PSE group were significantly lower than in the TIPS group, whereas the 5-year cumulative rates of shunt blockage (12.5% vs. 25.8%, p = 0.388), and all-cause mortality (37.5% vs. 69.3%, p = 0.414) were not statistically different between the two groups. The 2-year cumulative rate of remaining free of hepatic encephalopathy was also similar between the two groups (75.0% vs. 81.3%, p = 0.704). Cox-regression analyses showed that group and reduction of portal venous pressure before and after TIPS creation were associated with both variceal rebleeding and shunt stenosis, whereas only reduction of portal venous pressure (hazard ratio 0.648, 95% confidence interval: 0.444-0.946, p = 0.025) was associated with shunt blockage. No severe adverse event was observed in the two groups. CONCLUSION: TIPS+PSE is superior to TIPS alone in control of variceal rebleeding and shunt stenosis. Further prospective studies are warranted to confirm our findings.

Prednisone is not beneficial for the treatment of severe drug-induced liver injury: An observational study (STROBE compliant).

There is limited information about the effects of corticosteroids on severe drug-induced liver injury (DILI). This study aimed to investigate the efficacy and safety of prednisone in severe DILI.Ninety patients with severe DILI were enrolled and studied retrospectively. They were divided into prednisone (n = 66) and control groups (n = 24), undergoing the same treatment regimen except that patients in the prednisone group received a median daily dose of 40 mg prednisone. The primary endpoint was severity reduction (serum total bilirubin [TBIL] <86 µmol/L).During the study, the cumulative rates of severity reduction at 4-, 8-, and 12 days were comparable between the 2 groups (prednisone versus control: 7.6%, 33.3%, and 60.6% versus 12.5%, 37.5%, and 66.7%, P = .331), and were markedly lower in the high-dose group than in the low-dose group (0%, 28.6%, and 35.7% versus 9.6%, 34.6%, and 67.3%, P = .012) or in the control group (0%, 28.6%, and 35.7% versus 12.5%, 37.5%, and 66.7%, P = .023). The 30-day overall survival rate in the prednisone group was significantly higher than in the control group (100% versus 91.7%, P = .018). Serum bilirubin and transaminase values gradually decreased in both groups, which were not significantly different mostly. Cox-regression models revealed that baseline TBIL (hazard ratio: 0.235; 95% confidence interval: 0.084-0.665; P = .006) was the only predictor for severity reduction. No severe adverse event was noted in both groups.Prednisone therapy is safe but not beneficial, and even detrimental at a daily dose > 40 mg for the treatment of severe DILI.

Comparison of TIPS alone and combined with partial splenic embolization (PSE) for the management of variceal bleeding.

OBJECTIVES: Transjugular intrahepatic portosystemic shunt (TIPS) and partial splenic embolization (PSE) were two interventional radiological treatments for the complications of cirrhosis. This study aimed to investigate the effects of concomitant PSE on the long-term shunt patency and overall survival of TIPS-treated patients. METHODS: Forty-eight patients with TIPS insertion were enrolled and studied retrospectively. They were divided into TIPS+PSE (n = 16) and TIPS groups (n = 32), undergoing combined therapy using TIPS and PSE, and monotherapy using TIPS alone, respectively. RESULTS: The 5-year cumulative primary patency rate in the TIPS+PSE group was markedly higher than in the TIPS group (56.8% vs. 32.8%, p = 0.028), whereas the 5-year cumulative secondary patency rate (93.8% vs. 87.7%, p = 0.749) and overall survival rate (62.5% vs. 30.7%, p = 0.414) were not significantly different between the two groups. Cox-regression models revealed that group (hazard ratio [HR], 0.235; 95% CI, 0.084-0.665; p = 0.006), portal venous pressure decline (HR, 0.687; 95% CI, 0.563-0.838; p = 0.000), and baseline portal vein thrombosis (HR, 3.955; 95% CI, 1.634-9.573; p = 0.002) were significant predictors for shunt dysfunction, while only ascites (HR, 2.941; 95% CI, 1.250-6.920; p = 0.013) was a significant predictor for mortality. No severe adverse event was noted in the two groups except for the potential risk of splenic abscess development in the TIPS+PSE group. CONCLUSIONS: Concomitant PSE may help increase the long-term primary shunt patency rate, but not the overall survival of TIPS-treated patients. Further prospective studies are needed to validate these retrospective findings and to investigate the potential mechanisms. KEY POINTS: • Combined therapy using TIPS and PSE is associated with higher primary patency rates than TIPS alone. • Combined therapy using TIPS and PSE is associated with similar rates of secondary patency and overall survival of patients than TIPS alone. • Group (TIPS alone or TIPS+PSE), PVD, and baseline PVT are three independent predictors for shunt dysfunction, while ascites is the only independent predictor for mortality.

Tenofovir Versus Entecavir for the Treatment of Acute-on-Chronic Liver Failure due to Reactivation of Chronic Hepatitis B With Genotypes B and C.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) can be triggered by reactivation of chronic hepatitis B (CHB). Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are now the most potent antiviral agents for CHB. This study aimed to compare the short-term safety and efficacy of TDF with ETV in the treatment of ACLF due to reactivation of CHB [hepatitis B virus (HBV)-ACLF]. PATIENTS AND METHODS: In total, 67 consecutive patients with HBV-ACLF were divided into TDF group (n=32) receiving daily TDF (300 mg/d) and ETV group (n=35) receiving daily ETV (0.5 mg/d). They were prospectively followed-up and the primary endpoint was overall survival at 3 months. RESULTS: At 2 weeks, the TDF group had significantly higher HBV-DNA reduction (P=0.003), lower HBV-DNA level (P=0.001), higher rate of HBV-DNA undetectbility (P=0.007), lower Child-Turcotte-Pugh (CTP; P=0.003), and model for end-stage liver disease (P=0.002) scores than the ETV group. At 3 months, HBV-DNA was undetectable in all survived patients; CTP (P=0.970) and model for end-stage liver disease (P=0.192) scores were comparable between the 2 groups, but markedly lower than at baseline (P<0.01); the TDF group had significantly higher cumulative survival rate than the ETV group (P=0.025). The white blood cell count (hazard ratio, 2.726; 95% confidence interval, 2.691-7.897; P=0.000), and HBV-DNA reduction (hazard ratio, 0.266; 95% confidence interval, 0.033-0.629; P=0.013) at 2 weeks were independent predictors for mortality. Both drugs were well tolerated. CONCLUSIONS: The short-term efficacy of TDF was superior to ETV for the treatment of HBV-ACLF. The white blood cell count and HBV-DNA reduction at 2 weeks were independent predictors for mortality at 3 months.

Transjugular Intrahepatic Portosystemic Shunt:The Impact of Portal Venous Pressure Declines on Shunt Patency and Clinical Efficacy.

RATIONALE AND OBJECTIVES: Transjugular intrahepatic portosystemic shunt (TIPS) placement using the same-diameter covered stents can lead to differed declines of portal venous pressure declines (PVDs). This study aimed to compare the long-term shunt patency and clinical efficacy of TIPS placement that caused low PVDs (≤9 mmHg) and high PVDs (>9 mmHg). MATERIALS AND METHODS: A total of 129 patients treated by TIPS placement with 8 mm-diameter polytetrafluoroethylene covered stents were included and analyzed retrospectively. They were stratified into group A with low PVDs (n = 69) and group B with high PVDs (n = 60). RESULTS: The 6-year actuarial probabilities of remaining free of shunt dysfunction (47.2% vs 64.6%; p = 0.007) and variceal rebleeding (48.3% vs 63.9%; p = 0.038) were significantly lower in group A than in group B. The 6-year actuarial probability of remaining free of hepatic encephalopathy was significantly higher in group A than in group B (44.5% vs 32.5%; p = 0.010), though the 6-year cumulative survival rate was similar in both groups (A vs B: 65.5% vs 56.0%; p = 0.240). The baseline portal vein thrombosis (hazard ratio [HR]: 6.045, 95% confidence interval [CI]: 2.762-13.233; p = 0.000) and stent type (HR: 4.447, 95%CI: 1.711-11.559, p = 0.002) were associated with shunt dysfunction, whereas only ascites was associated with mortality (HR: 1.373, 95%CI: 1.114-3.215; p = 0.024). CONCLUSION: High PVDs (>9 mmHg) were associated with higher shunt patency, lower incidence of variceal rebleeding, but higher frequency of hepatic encephalopathy and similar survival rate than low PVDs (≤9 mmHg) after TIPS placement.

Genotype Matters in Patients with Acute-on-chronic Liver Failure Due to Reactivation of Chronic Hepatitis B.

BACKGROUND: Acute-on-chronic liver failure (ACLF) can be caused by reactivation of chronic hepatitis B virus (HBV) infection (HBV-ACLF). It's unclear whether HBV genotypes affect the clinical and therapeutical outcomes of patients with HBV-ACLF. This study was to investigate the short-term antiviral response and overall survival in HBV-ACLF patients treated by tenofovir or entecavir. METHODS: Seventy-three consecutive patients with HBV-ACLF were stratified into genotype B group (n = 33) and C group (n = 40). They were prospectively followed-up. RESULTS: At 2 weeks, the genotype B group had significantly lower HBV-DNA load (P = 0.005), greater HBV-DNA decline (P = 0.026), higher proportion of patients with HBV-DNA < 500 IU/ml (P = 0.007), improved Child-Turcotte-Pugh (CTP; P = 0.032) and model for end-stage liver disease (MELD; P = 0.039) scores compared to the genotype C group. At three months, survivors in both groups had undetectable HBV-DNA loads, comparable CTP (P = 0.850) and MELD (P = 0.861) scores; the genotype C group had markedly lower overall survival rate than the B group (P = 0.013). The genotype (hazard ratio [HR]: 2.138; 95% confidence interval [CI]: 1.034-4.143; P = 0.041), MELD score (HR:1.664, 95%CI: 1.077-2.571; P = 0.022) and HBV-DNA decline (HR: 0.225, 95% CI: 0.067-0.758; P = 0.016) at 2 weeks were significantly associated with mortality at 3 months. No severe adverse event was noted. CONCLUSIONS: Genotype B was associated with better short-term antiviral response and clinical outcome compared to genotype C in patients with HBV-ACLF.

Predictors of Shunt Dysfunction and Overall Survival in Patients with Variceal Bleeding Treated with Transjugular Portosystemic Shunt Creation Using the Fluency Stent Graft.

RATIONALE AND OBJECTIVES: Transjugular intrahepatic portosystemic shunt (TIPS) is an established method for portal hypertension. This study was to investigate the long-term safety, technical success, and patency of TIPS, and to determine the risk factors and clinical impacts of shunt dysfunction. MATERIALS AND METHODS: A total of 154 consecutive patients undergoing embolotherapy of gastric coronary vein and/or short gastric vein and TIPS creation were prospectively studied. Follow-up data included technical success, patency and revision of TIPS, and overall survival of patients. RESULTS: During the study, the primary and secondary technical success rates were 98.7% and 100%, respectively. Sixty-three patients developed shunt dysfunction, 30 with shunt stenosis and 33 with shunt occlusion. The cumulative 60-month primary, primary assisted, and secondary patency rates were 19.6%, 43.0%, and 93.4%, respectively. The cumulative 60-month overall survival rates were similar between the TIPS dysfunction group and the TIPS non-dysfunction group (68.6% vs. 58.6%, P = .096). Baseline portal vein thrombosis (P < .001), use of bare stents (P = .018), and portal pressure gradient (PPG) (P = .020) were independent predictors for shunt dysfunction, hepatocellular carcinoma (P < .001), and ascites (P = .003) for overall survival. The accuracy of PPG for shunt dysfunction was statistically significant (P < .001), and a cutoff value of 8.5 had 77.8% sensitivity and 64.8% specificity. CONCLUSIONS: The long-term safety, technical success, and patency of TIPS were good; baseline portal vein thrombosis, use of bare stents, and PPG were significantly associated with shunt dysfunction; shunt dysfunction has little impact on patients' long-term survival because of high secondary patency rates.

The Effect of Transarterial Chemoembolization in Combination With Kang'ai Injection on Patients With Intermediate Stage Hepatocellular Carcinoma: A Prospective Study.

BACKGROUND: The outcome of patients with intermediate stage hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE) remains poor. Search for a more effective therapy is still necessary. OBJECTIVE: This study aimed to investigate the effect of combining TACE with Kang'ai (KA) injection for treating patients with intermediate stage HCC. METHODS: A total of 89 patients with intermediate stage HCC were enrolled and divided into TACE +KA group (n = 48) receiving repeated TACE plus KA injection, and TACE group (n = 41) receiving repeated TACE alone. All patients were prospectively studied. Primary endpoints were overall survival (OS) and time to radiologic progression (TTP). RESULTS: The TACE + KA group had significantly longer median OS (27.0 vs 21.0 months, P = .038) and TTP (12.0 vs 10.0 months, P = .028) than TACE group. The 1-, 2-, and 3-year OS rates in the TACE + KA group were markedly higher than in TACE group (88.5%, 58.8%, and 20.8% vs 81.3%, 44.9%, and 6.7%, respectively, P = .038), while the 1- and 2-year TTP rates in the TACE + KA group were significantly lower than in TACE group (49.3% and 86.9% vs 75.3% and 100%, P = .028). TACE + KA group displayed significantly lower incidences of intrahepatic and extrahepatic metastases, as well as postembolization syndrome than TACE group ( P < .05). Multivariate analyses revealed group ( P = .023), maximum tumor size ( P = .019), and tumor number ( P = .034) as significant predictors for OS, and group ( P = .046), maximum tumor size ( P = .002) and α-fetoprotein level ( P = .020) as significant predictors for TTP. Both TACE and KA injection were well tolerated. CONCLUSION: TACE plus KA injection is more effective than TACE alone for treating patients with intermediate stage HCC in this nonrandomized study. Further research is warranted.

Portal vein thrombosis before and after transjugular intrahepatic portosystemic shunt placement: An observational study (STROBE compliant).

Portal vein thrombosis (PVT) is common in patients with cirrhosis undergoing transjugular intrahepatic portosystemic shunt (TIPS). This study had 3-fold aims: to assess risk factors for PVT; to determine the efficacy of anticoagulant therapy; to investigate the impact of PVT on clinical outcomes in TIPS-treated cirrhosis.Between June 2012 and February 2016, 126 TIPS-treated patients with cirrhosis were enrolled and studied prospectively. Enrolled patients were screened for PVT before TIPS and at 3, 6, 12, and 24 months post-TIPS. All patients received warfarin (1.5-3.0 mg/day) or aspirin (100 mg/day) or clopidogrel (75 mg/day) post-TIPS. Results of patients with and without PVT (baseline and de novo) were compared.White blood cell (WBC) counts (odds ratio (OR): 0.430, 95% confidence interval (CI): 0.251-0.739, P = .002) and Child-Turcotte-Pugh (CTP) score (OR: 2.377, 95% CI: 1.045-5.409, P = .039) were significant baseline predictors for PVT in TIPS-treated patients with cirrhosis. Warfarin resulted in markedly greater rates of complete recanalization than aspirin or clopidogrel (P < .05) in patients with PVT. Patients with PVT had markedly higher 2-year cumulative rates of variceal rebleeding, shunt dysfunction, hepatic encephalopathy, and hepatocellular carcinoma, and prominently lower overall survival than those without PVT (P < .05).In TIPS-treated patients with cirrhosis, lower WBC count and higher CTP score were independent baseline predictors for PVT; patients with PVT had worse clinical outcomes than those without; warfarin may be more effective in recanalizing PVT than aspirin or clopidogrel.

[Studies on DNA damage of the neuron cell in rat offspring induced by cypermerthrin and methylparathrion during embryo exposure].

OBJECTIVE: To explore DNA damage of rat's brain prenatal exposure to mixed pesticides of cypermerthrin and methylparathrion. METHODS: 48 pregnant Wistar rats were divided into 4 groups. During the 1st to 15th day of gestation, all rats were force fed with mixed pesticides of cypermerthrin plug methylparathrion. The dosage of the two pesticides were (0, 1/300, 1/95 and 1/30) LD50, respectively. The brains of 24 embryos at the gestation day 16th (6 each group) and 24 rat offspring (6 each group) at the 30-day-old after birth were taken out respectively, and the single cell gel electrophoresis (SCGE or comet assay) was utilized to access DNA damage. RESULTS: At the exposure does of 1/95LD50 and 1/30LD50, the mixed pesticides could induce the neuron cell DNA strain rupture of the neuron cell of embryos remarkably (P < 0.05), while the high dose could induce the DNA damage in brain of 30-day-old rats (P < 0.05). The DNA damage in brain neurons of rat offspring was more severe with increased doses of mixed pesticides (correlation analysis: DNA damage at embryos, r = 0.836, P = 0.000). Especially at dose of 1/95 LD50, 1/30 LD50, the DNA damage in brain of the 30-day-old rats was more severe than the embryo rats (F = 15.81, P < 0.0001). CONCLUSION: Prenatally exposed to mixed pesticides of cypermerthrin plus methyl parathion could cause neuron cell DNA damage. At the lower level, DNA damage of the neuron of rat offspring could be repaired, but the repair was difficult at the higher level.

[Effects of NMDA receptor expression in rat's hippocampus after exposure to 1800 MHz radiofrequency field].

OBJECTIVE: To identify the effects of NMDA receptor subunits NR2A and NR2B expression in rat's hippocampus after exposure to 1800 MHz radiofrequency radiation. METHODS: Four-week old female Wistar rats were randomly divided into four groups, with 12 animals for each. The subjects in two experimental groups had been continuously exposed to 1800 MHz microwave radiation (CW) with respective power density of 0.5 mW/cm(2) and 1.0 mW/cm(2) 12 hours each day for 21 days. Meanwhile, sham-controls were carried out. The brain tissue sections were performed by immunohistochemistry to demonstrate both expressions of NR2A, NR2B immune-activity in the hippocampal CA1, CA3 and DG by using computer-assisted image analysis system. RESULTS: In NR2A: the expression of 0.5 mW/cm(2) power density group was significantly lower than 0 mW/cm(2) power density group in CA3 [(8.5 +/- 1.5) vs (11.1 +/- 1.8), P < 0.01] and had not been significantly changed in CA1 and DG. The expression of 1.0 mW/cm(2) power density group was significantly lower than 0 mW/cm(2) power density group in CA1 and CA3 [(7.9 +/- 1.6) vs (9.7 +/- 1.5); (8.4 +/- 1.7) vs (11.1 +/- 1.8), respective P < 0.05, P < 0.01] and had not been significantly changed in DG. In NR2B: the expression of 0.5 mW/cm(2) power density group was significantly lower than 0 mW/cm(2) power density group in CA1 and CA3 [(16.4 +/- 1.0) vs (17.8 +/- 1.6); (9.6 +/- 1.9) vs (11.2 +/- 2.1), respective P < 0.05]. The expression of 1.0 mW/cm(2) power density group was significantly lower than 0 mW/cm(2) power density group in CA1, CA3 and DG [(13.1 +/- 2.4) vs (17.8 +/- 1.6); (9.3 +/- 1.4) vs (11.2 +/- 2.1); (7.3 +/- 0.1) vs (8.5 +/- 1.0), respective P < 0.01, P < 0.05, P < 0.05]. CONCLUSION: There were findings of the effects on NMDA receptor subunits in different hippocampus sections after exposure to 1800 MHz radiofrequency radiation.