scholarly journals Effect of Histone Deacetylase HDAC3 on Cytokines IL-18, IL-12 and TNF-α in Patients with Intrahepatic Cholestasis of Pregnancy

2017 ◽  
Vol 42 (4) ◽  
pp. 1294-1302 ◽  
Author(s):  
Yong Shao ◽  
Jing Chen ◽  
Jiao Zheng ◽  
Cai-Ru Liu
Keyword(s):  
Protein Expression ◽  
Histone Deacetylase ◽  
Intrahepatic Cholestasis ◽  
Serum Levels ◽  
Hepatic Function ◽  
Control Group ◽  
Intrahepatic Cholestasis Of Pregnancy ◽  
Tnf Α ◽  
Significant Difference ◽  
Cholestasis Of Pregnancy

Background/aims: The pathogenesis of intrahepatic cholestasis of pregnancy (ICP) is poorly understood. Objective: This study aimed to explore the possible effect of HDAC3 (histone deacetylase) on cytokines IL-18, IL-12 and TNF-α in ICP. Methods: Serum levels of cytokines IL-18, IL-12 and TNF-α, bile acids and hepatic function parameters were measured. The expression of HDAC3 in the placenta was determined by immunohistochemistry (IHC), western blotting and RT-PCR. Results: IL-18, IL-12 and TNF-α serum levels were significantly higher in the severe ICP group than in the mild ICP group and the control group, and the difference between the mild ICP group and control group was not significant. HDAC3 protein expression was identified in the nucleus of the placental trophoblast by IHC. HDAC3 mRNA and protein expression were significantly lower in the ICP groups (mild ICP and severe ICP groups) than in the control groups, and no significant difference was found between the mild ICP and severe ICP groups. Conclusions: The low expression of HDAC3 and overexpession of inflammatory cytokines (IL-18, IL-12 and TNF-α) in ICP may be involved in liver cell apoptosis. We suspect that HDAC3 may play an important role in the pathophysiology of ICP.

l-Carnitine-induced amelioration of HFD-induced hepatic dysfunction is accompanied by a reduction in hepatic TNF-α and TGF-β1

2018 ◽  
Vol 96 (6) ◽  
pp. 713-725 ◽  
Author(s):  
Mabrouk Attia Abd Eldaim ◽  
Fatma Mohamed Ibrahim ◽  
Saher Hassan Orabi ◽  
Azza Hassan ◽  
Hesham Saad El Sabagh
Keyword(s):  
Protein Expression ◽  
High Density Lipoprotein ◽  
Body Mass ◽  
Density Lipoprotein ◽  
Basal Diet ◽  
Serum Levels ◽  
High Density ◽  
Control Group ◽  
Tnf Α ◽  
Tgf Β1

In this study, we evaluated the possible mechanisms through which l-carnitine ameliorates the adverse effects from obesity in rats, induced with a high-fat diet (HFD). For this, 56 albino Wister rats were randomly assigned to 7 groups. The control group was fed a basal diet and injected with saline. The second group was fed the basal diet and injected with l-carnitine (200 mg/kg body mass, by intraperitoneal injection; i.p.). The third group were fed the HFD. The fourth group was fed the HFD and injected with l-carnitine (200 mg/kg body mass, i.p.) for 8 weeks. The fifth group was fed the HFD for 10 weeks. The sixth group were fed the HFD for 10 weeks and were also injected with l-carnitine (200 mg/kg body mass, i.p.) during the final 2 weeks. The seventh group was fed the HFD diet for 8 weeks then the basal diet for 2 weeks. The HFD induced significantly increased levels of hyperglycemia, lipid peroxidation, pathological changes, TNF-α and TGF-β1 protein expression in hepatic tissue, food intake, body weight gain, serum levels of total and non-high-density lipoprotein cholesterol, ketone bodies, triacylglycerol, urea, creatinine, AST, and ALT. However, the HFD diet significantly decreased serum levels of high-density lipoprotein (HDL) and hepatic levels of reduced glutathione. l-Carnitine ameliorated the effects of the HFD on the above-mentioned parameters. This study indicated that l-carnitine had protective and curative effects against HFD-induced hepatosteatosis by reducing hepatic oxidative stress and protein expression of TNF-α and TGF-β1.

Association of ABCB4 and ABCB11 nucleotide variants with intrahepatic cholestasis of pregnancy

2019 ◽  
Vol 88 (4) ◽  
pp. 209-217
Author(s):  
Milena Gruszczyńska-Losy ◽  
Adrianna Mostowska ◽  
Łukasz Adamczak ◽  
Paweł Jagodziński ◽  
Ewa Wender-Ożegowska ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Intrahepatic Cholestasis ◽  
Clinical Symptoms ◽  
Melting Curve ◽  
Liver Disorder ◽  
Melting Curve Analysis ◽  
Control Group ◽  
Intrahepatic Cholestasis Of Pregnancy ◽  
Increased Risk ◽  
Cholestasis Of Pregnancy

Background: Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disorder during gestation. The exact pathogenesis of ICP is multifactorial and still unclear. Therefore, our study aimed to check whether the selected ABCB4and ABCB11nucleotide variants are associated with an increased risk of ICP. Methods:ICP was diagnosed based on clinical symptoms characteristic of this disease and confirmed by increase in serum bile acids and transaminases, spontaneous resolution of clinical symptoms and normalization of laboratory tests after delivery. The total of 86 pregnant women meeting the criteria were included into the study. Healthy pregnant women with uncomplicated pregnancy served as control group (n=310). Sixcommon nucleotide variants in theABCB11and ABCB4genes were genotypedwith the use of high-resolution melting curve analysis. Conclusion:Our study did not show any significant association of analysed ABCB4and ABCB11nucleotide variants with the increased risk of intrahepatic cholestasis of pregnancy.

scholarly journals A Randomized Control Trial Study to Determine the Effect of Melatonin on Serum Levels of IL-1β and TNF-α in Patients with Multiple Sclerosis

2020 ◽  
Author(s):  
Masoomeh Yosefifard ◽  
Gholamhassan Vaezi ◽  
Ali Akbar Malekirad ◽  
Fardin Faraji ◽  
Vida Hojati
Keyword(s):  
Multiple Sclerosis ◽  
Interleukin 1 ◽  
Serum Levels ◽  
Inflammatory Factors ◽  
Control Group ◽  
Necrosis Factor Alpha ◽  
Treatment Groups ◽  
Tnf Α ◽  
Significant Difference ◽  
The Central Nervous System

Multiple sclerosis (MS) is the most common neurological disease that happens at a young age. MS is an inflammatory disease; associated with the demyelination of the central nervous system. Therefore, some inflammatory factors are effective in the mechanism and progression of the disease. Melatonin, as a multi-effect substance including anti-inflammatory effects, can reduce symptoms of MS in patients with a change in their inflammatory factors level. In this study, 50 MS patients who were referred to the MS Society of Markazi Province were randomly selected. All patients were treated with routine MS treatment (interferon) and were divided into control (25 placebo recipients) and treatment (25 recipients of 3 mg melatonin per day for 24 weeks) groups. Anthropometric data of patients including height, weight, and age were determined. Blood samples were collected after fasting in order to determine serum levels of interleukin 1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α). Then, samples were immediately centrifuged for serum separation and sera were transferred to a freezer at -80°C and serum levels of these factors were determined; using ELISA kit. The results of this study showed that there was no significant difference between the control and treatment groups in terms of serum levels of TNF-α. However, the level of IL-1β was significantly reduced in the treatment group compared to the control group, indicating that melatonin decreases this inflammatory substance. Our findings suggest a valuable strategy in the treatment of patients who suffer from MS

The Role of Melatonin, IL-8 and IL-10 in Intrahepatic Cholestasis of Pregnancy

2020 ◽  
Author(s):  
Samettin Çelik ◽  
Huri Guve ◽  
Canan Çalışkan ◽  
Sebahattin Çelik
Keyword(s):  
Intrahepatic Cholestasis ◽  
Inflammatory Cytokine ◽  
Elevated Serum ◽  
Interleukin 10 ◽  
Interleukin 8 ◽  
Controlled Study ◽  
Control Group ◽  
Intrahepatic Cholestasis Of Pregnancy ◽  
Cholestasis Of Pregnancy

Abstract Introduction Intrahepatic cholestasis of pregnancy is a pregnancy-specific liver disease that usually emerges during the third trimester of pregnancy. It is characterized by itching and elevated serum total bile acid levels, and it may lead to severe fetal complications. This study aimed to investigate the role of interleukin-8, a pro-inflammatory cytokine; interleukin-10, an anti-inflammatory cytokine; and melatonin in intrahepatic cholestasis of pregnancy. Materials and Methods This prospective, case-controlled study was conducted with 51 women with intrahepatic cholestasis of pregnancy (40 mild and 11 severe cases) and 43 healthy pregnant women. Serum interleukin-8, interleukin-10, and melatonin levels were evaluated. Results Melatonin and interleukin -10 were significantly lower in subjects with intrahepatic cholestasis of pregnancy (p=0.001; p=0.001, respectively p<0.05). Interleukin-8 levels were found to be significantly higher in the cholestasis group than control group (p=0.001, p<0.05). Conclusions Because interleukin-8, interleukin-10, and melatonin were found to be significantly correlated with intrahepatic cholestasis of pregnancy, we believe this finding could shed light on the etiology of the disease.

scholarly journals Intrahepatic Cholestasis in Pregnancy: Review of the Literature

2020 ◽  
Vol 9 (5) ◽  
pp. 1361
Author(s):  
Joanna Piechota ◽  
Wojciech Jelski
Keyword(s):  
Intrahepatic Cholestasis ◽  
Clinical Symptoms ◽  
Clinical Signs ◽  
Serum Levels ◽  
Premature Delivery ◽  
Intrahepatic Cholestasis Of Pregnancy ◽  
Perinatal Complications ◽  
Hepatic Disorder ◽  
Increased Risk ◽  
Cholestasis Of Pregnancy

Intrahepatic cholestasis of pregnancy (ICP) is the most common hepatic disorder related to pregnancy in women. It usually develops within the third trimester of pregnancy and presents with pruritus as well as elevated levels of bile acid and/or alanine aminotransferase. Clinical signs quickly resolve after delivery; however, there is a high risk of the disorder recurring in subsequent pregnancies. ICP is associated with an increased risk of perinatal complications (premature birth, respiratory disorders, even stillbirth). Elevated levels of gestational hormones and genetic predispositions are important factors for the development of ICP; among the latter, mutations in hepatobiliary transport proteins (multidrug resistance protein 3-MDR3, bile salt export pump- BSEP) play a major role. Clinical and biochemical symptoms of ICP include pruritus and increased levels of total bile acids (TBA). Serum levels of TBA should be monitored in ICP patients throughout the pregnancy as concentrations above 40 μmol/L, which define that severe ICP isassociated with an increased risk of fetal complications. Therapeutic management is aimed at reducing the clinical symptoms, normalizing maternal biochemistry and preventing complications to the fetus. Pharmacological treatment of intrahepatic cholestasis of pregnancy consists of the administration of ursodeoxycholic acid to lower the levels of TBA and possibly reduce pruritus. If the treatment fails, premature delivery should be considered.

scholarly journals Protection of Ang1-7 througth MKK/P38MAPKs inflammatory signal pathway on TNF-α stimulated mouse HL-1 cells

2021 ◽  
Author(s):  
Xuewen Wang ◽  
Yuan Cao ◽  
Pradeep depark ◽  
Deepark Sharma ◽  
Guangping Li ◽  
...  
Keyword(s):  
Protein Expression ◽  
Signal Pathway ◽  
Inflammatory Factors ◽  
Control Group ◽  
Inflammatory Factor ◽  
Tnf Α ◽  
Significant Difference ◽  
Atrial Myocyte ◽  
Group B ◽  
Group Control Group

Abstract Background to explore the effect of Ang1-7 througth MKK/P38MAPKs inflammatory signaling pathway on TNF-α-stimulated mouse HL-1 cells. Methods Using TNF-α (100 µg/ml) to establish an inflammatory atrial fibrillation model in HL-1 cell, which derived from mouse atrial myocyte. treated HL-1 cells with different concentrations of Ang 1-7 (0.1, 1 and 10 mmol/L) and divided into 5 groups, namely A group(control group), B group(TNF ), C group(TNF + Ang 1-7 0.1 mmol/L), D group(TNF + Ang 1-7 1 mmol/L ) and E group(TNF + Ang 1-7 10 mmol/L ). Firstly, different concentrations of Ang 1-7 (0.1 mmol/L, 1 mmol/L and 10 mmol/L) were used to stimulate for half an hour, and then TNF-α (100 µg/ml) was added to stimulate for four hours. Both the cells and supernatant were collected. Cells were collected for Western Blotting to detect the protein expression of MKK3, MKK4, MKK6, PMMK4 and PP38. The supernatant was subjected to flow cytometry for detecting multi-inflammatory factors. Results Compared with the A group, the protein expression of MKK3, MKK4, MKK6, PMMK4 and PP38 was statistically significant increased after stimulation with inflammatory factors (TNF-α) (P < 0.05). After intervention with Ang 1-7, the protein expression of MKK3, MKK4, MKK6, PMMK4 and PP38 was statistically significant lower than that of B group (P < 0.05). There is no significant difference of the protein expression of P38 after stimulation with inflammatory factor (TNF-α). Compared with the A group, there was no significant difference in the protein expression of MAS after the stimulation of inflammatory factor (TNF-α). After the intervention of Ang 1-7, the protein expression of MAS was higher than that of the A group and B group, but there was no significant difference (P > 0.05). The expression of MAS protein had an increasing trend, but there was no significant difference (P > 0.05). TGF-β, TNF-α was significantly increased after stimulating factor (TNF-α) was given, but was decreased after the intervention of Ang 1-7, both there were statistically significant (P < 0.05). IL-6 also had the same trend, but there was no significant difference. Conclusion Ang1-7 througth MKK/P38MAPKs inflammatory signal pathway protected on TNF-α stimulated mouse HL-1 cells

scholarly journals Ursodeoxycholic acid to reduce adverse perinatal outcomes for intrahepatic cholestasis of pregnancy: the PITCHES RCT

2020 ◽  
Vol 7 (9) ◽  
pp. 1-42
Author(s):  
Lucy C Chappell ◽  
Jennifer L Bell ◽  
Anne Smith ◽  
Catherine Rounding ◽  
Ursula Bowler ◽  
...  
Keyword(s):  
Placebo Group ◽  
Ursodeoxycholic Acid ◽  
Intrahepatic Cholestasis ◽  
Primary Outcome ◽  
Perinatal Outcomes ◽  
Acid Group ◽  
Intrahepatic Cholestasis Of Pregnancy ◽  
Significant Difference ◽  
Adverse Perinatal Outcomes ◽  
Cholestasis Of Pregnancy

Background Intrahepatic cholestasis of pregnancy, characterised by maternal pruritus and raised serum bile acid concentrations, is associated with increased rates of stillbirth, preterm birth and neonatal unit admission. Ursodeoxycholic acid is widely used as a treatment, but without an adequate evidence base. Objective We aimed to evaluate whether or not ursodeoxycholic acid reduces adverse perinatal outcomes in affected women. Design Multicentre, masked, randomised, placebo-controlled, two-arm, parallel-group trial. Setting Thirty-three UK maternity units. Participants Women with intrahepatic cholestasis of pregnancy aged ≥ 18 years, between 20+0 and 40+6 weeks’ gestation with a singleton or twin pregnancy and no known lethal fetal anomaly. Interventions Women were randomly assigned (1 : 1 allocation ratio) to take ursodeoxycholic acid tablets or matched placebo tablets, at an equivalent dose of 1000 mg daily, titrated as needed. Main outcome measures The primary outcome was a composite of perinatal death (in utero fetal death after randomisation or known neonatal death up to 7 days) or preterm delivery (< 37 weeks’ gestation) or neonatal unit admission for at least 4 hours (from birth until hospital discharge). Each infant was counted once within this composite. Analyses were by intention to treat. Results Between 23 December 2015 and 7 August 2018, 605 women were randomised, with 305 women allocated to the ursodeoxycholic acid arm and 300 women to the placebo arm. There was no evidence of a significant difference in the incidence of the primary outcome between the groups: 23.0% (74 out of 322 infants) in the ursodeoxycholic acid group compared with 26.7% (85 out of 318 infants) in the placebo group; adjusted risk ratio 0.85 (95% confidence interval 0.62 to 1.15). There was no evidence of a significant difference in total costs (maternal, infant and the cost of ursodeoxycholic acid) between the two trial groups. There were two serious adverse events in the ursodeoxycholic acid group and six in the placebo group. Limitations Limitations include a primary outcome event rate in the control group that was lower than that estimated for the sample size calculation, but the lack of evidence of effect in all analyses suggests that it is unlikely that the trial had insufficient power. Conclusions In this clinical trial of ursodeoxycholic acid in women with intrahepatic cholestasis of pregnancy, there is no evidence that it is effective in reducing a composite of adverse perinatal outcomes. Future work Future research should aim to elucidate the aetiology and pathophysiology of adverse perinatal outcomes, particularly stillbirth, in women with intrahepatic cholestasis of pregnancy to assist the development of an effective preventative treatment. Further exploratory analyses may identify groups of women who might respond to ursodeoxycholic acid treatment. Trial registration Current Controlled Trials ISRCTN91918806. Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) Programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 7, No. 9. See the NIHR Journals Library website for further project information.

scholarly journals Maternal and fetal outcome in intrahepatic cholestasis of pregnancy at tertiary care institute of North India

2021 ◽  
Vol 0 ◽  
pp. 1-5
Author(s):  
Sunita Arora ◽  
Anju Huria ◽  
Poonam Goel ◽  
Jasbinder Kaur ◽  
Sunita Dubey
Keyword(s):  
Bile Acids ◽  
Intrahepatic Cholestasis ◽  
Liver Enzymes ◽  
Tertiary Care ◽  
Population History ◽  
Whole Body ◽  
Control Group ◽  
Intrahepatic Cholestasis Of Pregnancy ◽  
Initial Visit ◽  
Cholestasis Of Pregnancy

Objectives: Intrahepatic cholestasis of pregnancy (IHCP) is the most common reversible form of hepatic disease in pregnancy. The risk of sudden intrauterine infant death is major threat as none of the fetal monitoring proved effective for its prevention. This study was conducted to know the prevalence of IHCP along with fetal and maternal outcome in North Indian population. Material and Methods: This case–control study was conducted over a period of 6 months. One hundred pregnant patients were recruited in each group. Patients with IHCP were included in case group whereas apparently healthy pregnant women with singleton pregnancy were included in control group. Bile acids were done only once at the time of initial visit whereas liver enzymes were done at initial visit and subsequently weekly for total 3 times. All cases of IHCP were started on ursodeoxycholic acid (UDCA) with a dose of 10–15 mg/kg/day throughout pregnancy and three doses of 10 mg Vitamin K by intramuscular route were also given. Fetal and maternal outcomes were compared between both the groups. Total numbers of deliveries in that time period were also noted to find out the prevalence of disease. The tests of two or more proportions were done using Fisher’s exact test and Chi-square test. P < 0.05 was considered statistically significant. Results: The prevalence of IHCP was 4.08% in our population, however, women from urban area had higher incidence of cholestasis than rural population. History of recurrent disease was found in 30% of women. Out of 100, 96% presented with itching and only 57–58% had raised liver enzymes levels. In 89% of patients (89/100), bile acids levels were >14 μmol/l. During follow-up, SGOT and SGPT levels were significantly improved over 2-week interval while on treatment with UDCA; however, levels were still on higher side. There was no correlation found between cholestasis of pregnancy with preterm labor and meconium-stained liquor in the present study. Comparable results were found in terms of respiratory distress syndrome and NICU admission, whereas significant high incidence of neonatal jaundice found in the control group. Conclusion: Itching over whole body was the predominant presenting complaints of cholestasis of pregnancy. Diagnosis should be supported by bile acids in women with normal liver enzymes to decrease the cost of investigations. Early termination of pregnancy between 36 and 37 weeks can be considered in women with bile acids >40 μmol/L and in non-compliant patients on UDCA treatment.

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