Ameliorating effects of adropin on letrozole-induced polycystic ovary syndrome via regulating steroidogenesis and the microbiota inflammatory axis in rats.

Growing evidence supports the role of gut microbiota in chronic inflammation, insulin resistance (IR) and sex hormone production in polycystic ovary syndrome (PCOS). Adropin plays a pivotal role in the regulation of glucose and lipid metabolism and is negatively correlated with IR, which affects intestinal microbiota and sex hormones. However, the effect of adropin administration in PCOS has yet to be investigated. The present study aimed to assess the effects of adropin on letrozole (LTZ)-induced PCOS in rats and the potential underlying mechanisms. The experimental groups were normal, adropin, letrozole and LTZ + adropin. At the end of the experiment, adropin significantly ameliorated PCOS, as evidenced by restoring the normal ovarian structure, decreasing the theca cell thickness in antral follicles, as well as serum testosterone and luteinizing hormone levels and luteinizing hormone/follicle-stimulating hormone ratios, at the same time as increasing granulosa cell thickness in antral follicles, oestradiol and follicle-stimulating hormone levels. The ameliorating effect could be attributed to its effect on sex hormone-binding globulin, key steroidogenic genes STAR and CYP11A1, IR, lipid profile, gut microbiota metabolites-brain-ovary axis components (short chain fatty acids, free fatty acid receptor 3 and peptide YY), intestinal permeability marker (zonulin and tight junction protein claudin-1), lipopolysaccharides/Toll-like receptor 4/nuclear factor kappa B inflammatory pathway and oxidative stress makers (malondialdehyde and total antioxidant capacity). In conclusion, adropin has a promising therapeutic effect on PCOS by regulating steroidogenesis, IR, lipid profile, the gut microbiota inflammatory axis and redox homeostasis. KEY POINTS: Adropin treatment reversed endocrine and ovarian morphology disorders in polycystic ovary syndrome (PCOS). Adropin regulated the ovarian steroidogenesis and sex hormone-binding globulin in PCOS. Adropin improved lipid profile and decreased insulin resistance in PCOS. Adropin modulated the components of the gut-brain-ovary axis (short chain fatty acids, free fatty acid receptor 3 and peptide YY) in PCOS. Adropin improved intestinal barrier integrity, suppressed of lipopolysaccharides/Toll-like receptor 4/nuclear factor kappa B signalling pathway and oxidative stress in PCOS.

Exercise Training and Spexin Ameliorate Thyroid Changes in Obese Type 2-Diabetic Rats: The Possible Interlaying Mechanisms.

Thyroid dysfunction and diabetes mellitus are prevalent endocrine disorders that often coexist and influence each other. The role of spexin (SPX) in diabetes and obesity is well-documented, but its connection to thyroid function is less understood. This study investigates the influence of exercise (EX) and SPX on thyroid hypofunction in obese type 2 diabetic rats. Rats were divided into normal control, obese diabetic sedentary, obese diabetic EX, and obese diabetic SPX groups, with subdivisions for M871, and HT-2157 treatment in the later 2 groups. High-fat diet together with streptozotocin injection induced obesity and diabetes. The EX-group underwent swimming, while the SPX-group received SPX injections for eight weeks. Results showed significant improvements in thyroid function, metabolic, oxidative, and inflammatory states with EX and SPX-treatment. The study also explored the involvement of galanin receptor isoforms (GALR) 2/3 in SPX effects on thyroid function. Blocking GALR2/3 receptors partially attenuated the beneficial effects, indicating their interaction. These findings underscore the importance of EX and SPX in modulating thyroid function in obesity and diabetes. Comprehending this interplay could enable the development of new treatment approaches for thyroid disorders associated with obese type 2 diabetes. Additional research is necessary to clarify the exact mechanisms connecting SPX, EX activity, and thyroid function.

The potential neuroprotective effects of Spirulina platensis in a valproic acid-induced experimental model of autism in the siblings of albino rats: targeting PIk3/AKT/mTOR signalling pathway.

Introduction: Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders with poor social interaction, communication issues, aberrant motor movements, and limited repetitive interests and behaviour. Spirulina platensis (SP) contains several multi-nutrients and has a wide range of neuroprotective properties.Aim: The target of the current experiment is to detect the protective effects of S. platensis on valproic-induced autism in adult female albino rats' siblings for the first time.Materials and Methods: Twelve Pregnant rats were separated into four main groups; Group I (control); Group II (S. platensis); Group III (autistic group); and Group IV (autistic SP-treated group). Fifteen offspring pups from each group were sacrificed, brain was divided for biochemical analysis as superoxide dismutase and malondialdehyde were evaluated spectrophotometrically while interleukin-6, interleukin-12, Bcl-2-associated X protein, B-cell lymphoma-2, Beclin-1, brain-derived neurotrophic factor were assessed by ELISA, other division of brain were used for gene expression of PI3k, Akt and mTOR pathway, last division of brain were stained using (H&E) and Giemsa stains. Tumour necrosis factor alpha (TNF-α) and Synaptophysin (SYN) markers were used for immunohistochemical staining.Results: Autistic Group (III) showed an increment in levels of MDA, IL-6, IL12 and BAX while showing a decrement in SOD, Bcl-2 and Beclin-1 as well as increased PI3k, Akt and mTOR gene expression. Autistic Group (III) also exhibited hypocellularity and disorganization of hippocampal and prefrontal cortex cells. The autistic SP-treated group (IV) showed improvement in these biochemical markers and pathological changes. Our findings suggest that Spirulina platensis will be significant in managing autism.

Ulinastatin ameliorated streptozotocin-induced diabetic nephropathy: Potential effects via modulating the components of gut-kidney axis and restoring mitochondrial homeostasis.

Growing evidence supports the role of the gut-kidney axis and persistent mitochondrial dysfunction in the pathogenesis of diabetic nephropathy (DN). Ulinastatin (UTI) has a potent anti-inflammatory effect, protecting the kidney and the gut barrier in sepsis, but its effect on DN has yet to be investigated. This study aimed to assess the potential mitigating effect of UTI on DN and investigate the possible involvement of gut-kidney axis and mitochondrial homeostasis in this effect. Forty male Wistar rats were divided equally into four groups: normal; UTI-treated control; untreated DN; and UTI-treated DN. At the end of the experiment, UTI ameliorated DN by modulating the gut-kidney axis as it improved serum and urinary creatinine, urine volume, creatinine clearance, blood urea nitrogen, urinary albumin, intestinal morphology including villus height, crypt depth, and number of goblet cells, with upregulating the expression of intestinal tight-junction protein claudin-1, and counteracting kidney changes as indicated by significantly decreasing glomerular tuft area and periglomerular and peritubular collagen deposition. In addition, it significantly reduced intestinal and renal nuclear factor kappa B (NF-κB), serum Complement 5a (C5a), renal monocyte chemoattractant protein-1 (MCP-1), renal intercellular adhesion molecule 1 (ICAM1), and renal signal transducer and activator of transcription 3 (STAT3), mitochondrial dynamin related protein 1 (Drp1), mitochondrial fission 1 protein (FIS1), mitochondrial reactive oxygen species (ROS), renal hydrogen peroxide (H2O2), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. Furthermore, it significantly increased serum short chain fatty acids (SCFAs), and mitochondrial ATP levels and mitochondrial transmembrane potential. Moreover, there were significant correlations between measured markers of gut components of the gut-kidney axis and renal function tests in UTI-treated DN group. In conclusion, UTI has a promising therapeutic effect on DN by modulating the gut-kidney axis and improving renal mitochondrial dynamics and redox equilibrium.

The role of miR-433-3p in vascular calcification in type 2 diabetic patients: targeting WNT/ß-Catenin and RANKL/RANK/OPG signaling pathways.

BACKGROUND: Vascular calcification (VC) is a major predictor of cardiovascular diseases that represent the principal cause of mortality among type-2 diabetic patients. Accumulating data suggest the vital role of some microRNAs on vascular calcification as an epigenetic regulator. Thus, we assessed herein, the role of serum miR-433-3p in vascular calcification in type-2 diabetic patients. METHODS: Twenty healthy subjects (control group) and forty diabetic patients (20 without VC and 20 with VC) were involved in the study. miR-433-3p gene expression was measured. Runx2, Dickkopf-1 (DKK1), ß-catenin, Receptor activator of nuclear factor kappa-B ligand (RANKL), and osteoprotegerin (OPG) levels in serum were assessed by ELISA technique. RESULTS: Diabetes patients had significantly lower levels of miR-433-3p expression in comparison to the control group, with the lowest levels being found in diabetic patients with VC. Furthermore, Runx2, ß-catenin, and RANKL levels were significantly increased with concomitant lower DKK1 and OPG levels detected in the two diabetic groups especially those with VC. CONCLUSION: Collectively, the study documented that down-regulation of miR-433-3p may contribute to the development of VC through activating WNT/ß-Catenin and RANKL/RANK/OPG signaling pathways.

The potential protective effect of liraglutide on valproic acid induced liver injury in rats: Targeting HMGB1/RAGE axis and RIPK3/MLKL mediated necroptosis.

Valproic acid (VPA) is a commonly used drug for management of epilepsy. Prolonged VPA administration increases the risk of hepatotoxicity. Liraglutide is a glucagon-like peptide 1 receptor (GLP-1R) agonist that act as a novel antidiabetic drug with broad-spectrum anti-inflammatory and antioxidant effects. This study tested the protective effect of liraglutide against VPA-induced hepatotoxicity elucidating the possible underlying molecular mechanisms. Forty adult male rats were allocated in to four equally sized groups; Group I (control group) received oral distilled water and subcutaneous normal saline for 2 weeks followed by subcutaneous normal saline only for 2 weeks. Group II (liraglutide group) received subcutaneous liraglutide dissolved in normal saline daily for 4 weeks. Group III (valproic acid-treated group) received sodium valproate dissolved in distilled water for 2 weeks. Group IV (Combined valproic acid & liraglutide treated group) received valproic acid plus liraglutide daily for 2 weeks which was continued for additional 2 weeks after valproic acid administration. The hepatic index was calculated. Serum AST, ALT, GGT, and ALP activities were estimated. Hepatic tissue homogenate MDA, GSH, SOD, HMGB1, MAPK, RIPK1, and RIPK3 levels were evaluated using ELISA. However, hepatic RAGE and MLKL messenger RNA expression levels using the QRT-PCR technique. Hepatic NF-κB and TNF-α were detected immunohistochemically. Results proved that liraglutide coadministration significantly decreased liver enzymes, MDA, HMGB1, MAPK, RIPK1 RIPK3, RAGE, and MLKL with concomitant increased GSH and SOD in comparison to the correspondent values in VPA-hepatotoxicity group. Conclusions: Liraglutide's protective effects against VPA-induced hepatotoxicity are triggered by ameliorating oxidative stress, inflammation, and necroptosis.

Moderating Gut Microbiome/Mitochondrial Axis in Oxazolone Induced Ulcerative Colitis: The Evolving Role of ß-Glucan and/or, Aldose Reductase Inhibitor, Fidarestat.

A mechanistic understanding of the dynamic interactions between the mitochondria and the gut microbiome is thought to offer innovative explanations for many diseases and thus provide innovative management approaches, especially in GIT-related autoimmune diseases, such as ulcerative colitis (UC). ß-Glucans, important components of many nutritious diets, including oats and mushrooms, have been shown to exhibit a variety of biological anti-inflammatory and immune-modulating actions. Our research study sought to provide insight into the function of ß-glucan and/or fidarestat in modifying the microbiome/mitochondrial gut axis in the treatment of UC. A total of 50 Wistar albino male rats were grouped into five groups: control, UC, ß-Glucan, Fidarestat, and combined treatment groups. All the groups were tested for the presence of free fatty acid receptors 2 and 3 (FFAR-2 and -3) and mitochondrial transcription factor A (TFAM) mRNA gene expressions. The reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and ATP content were found. The trimethylamine N-oxide (TMAO) and short-chain fatty acid (SCFA) levels were also examined. Nuclear factor kappa ß (NF-kß), nuclear factor (erythroid-2)-related factor 2 (Nrf2) DNA binding activity, and peroxisome proliferator-activated receptor gamma co-activator-1 (PGC-1) were identified using the ELISA method. We observed a substantial increase FFAR-2, -3, and TFAM mRNA expression after the therapy. Similar increases were seen in the ATP levels, MMP, SCFA, PGC-1, and Nrf2 DNA binding activity. The levels of ROS, TMAO, and NF-kß, on the other hand, significantly decreased. Using ß-glucan and fidarestat together had unique therapeutic benefits in treating UC by focusing on the microbiota/mitochondrial axis, opening up a new avenue for a potential treatment for such a complex, multidimensional illness.

Heat shock protein 47 as indispensible participant in liver fibrosis: Possible protective effect of lactoferrin.

Lactoferrin (LF) was previously suggested to have a protective effect against liver fibrosis by preventing hepatic stellate cells (HSCs) activation. The effect of LF on heat shock protein 47 (HSP47) has not yet been studied so this study was designed to investigate LF effect on HSP47 as a potential target for management of liver fibrosis and comparing it with silymarin (SM) in a thioacetamide (TAA)-induced liver fibrosis model. Rats were divided into four groups; normal control, TAA (TAA-treated), LF (LF + TAA-treated), and SM (SM + TAA-treated). After 6 weeks, both LF and SM improved the grade of cirrhosis, reduced collagen fibers deposition, inactivated HSCs, significantly decreased elevated liver enzymes, HSP47, hydroxyproline content, transforming growth factor-beta 1, matrix metalloproteinase-2, 8-hydroxydeoxyguanosine, malondialdehyde, nitric oxide levels and the percentage of alpha smooth muscle actin positive HSCs compared with TAA group. Moreover, LF significantly increased the total antioxidant capacity compared with TAA group. It could be concluded that LF is a promising antifibrotic drug and could be considered as one of the HSP47 inhibitors but SM is still more potent. © 2018 IUBMB Life, 70(8):795-805, 2018.

Vildagliptin Recruits Regulatory T Cells in Patients Undergoing Primary Percutaneous Coronary Intervention.

Regulatory T cells (Treg) has been documented to be protective against myocardial ischemia-reperfusion injury (MIRI). The administration of drugs which recruit Treg cells may participate in the cardioprotection of MIRI. The purpose of the present study was to investigate whether the add-on vildagliptin (vild) to standard treatment of MIRI prior to reperfusion could increase Treg recruitment, anti-inflammatory, and antioxidant effects of the standard treatment or not. Sixty diabetic patients with ST-segment elevation myocardial infarction were randomly divided into two equal groups: control group was given the standard medical treatment and vild group was given the standard medical treatment plus vild. There were no statistical differences between the mean of percentage of changes in nitric oxide, ischemia modified albumin, highly sensitive C reactive protein, and interferon-gamma levels in the studied groups. While, the percentages of changes of myeloperoxidase level, CD4+CD25+ Treg cells count, and transforming growth factor-beta1 level were significantly higher in vild group compared with control group. We concluded that addition of vild to standard medical treatment of MIRI could increase its effectiveness through recruitment of CD4+CD25+ Treg cells.

Gastroprotective effects of montelukast and Nigella sativa oil against corticosteroid-induced gastric damage: they are much more than antiasthmatic drugs.

Corticosteroids are used to treat a variety of diseases like bronchial asthma. However, long-term corticosteroids have a gastric ulcerogenic potential. Montelukast (MTK) and Nigella sativa oil (NSO) are used in treatment of bronchial asthma. Previous studies showed that MTK and NSO had gastroprotective effects in other models of gastric ulcer. The present study assesses synergistic gastroprotective effects of both drugs in dexamethasone (DXM)-induced gastric damage. Fifty male rats were divided into 5 groups: normal control (I), DXM group (II), MTK + DXM group (III), NSO + DXM group (IV), MTK + NSO + DXM group (V). After 7 days, stomachs were removed for biochemical analysis and histological examinations. Significant increases in malondialdehyde (MDA) level, superoxide dismutase (SOD) activity, myeloperoxidase (MPO) activity, and proliferating cell nuclear antigen (PCNA) positive cells, with significant decreases in mucus secretion were detected in DXM-treated group compared with group I. Meanwhile, significant decreases of MDA level, MPO activity, and PCNA positive cells and significant increases in mucus secretion were detected in treated groups compared with group II. SOD activity significantly decreased in group V compared with group II. We could conclude that administration of either MTK or NSO or both with DXM counteracts DXM-induced gastric lesions.

Irisin levels in relation to metabolic and liver functions in Egyptian patients with metabolic syndrome.

Irisin is a new myokine that is suspected to influence metabolic syndrome (MetS). However, there is a great controversy with respect to its level in cases of MetS and its correlation with different metabolic parameters. The present study assesses irisin levels in MetS patients and studies its relationship to metabolic and liver functions to evaluate the possible role of the liver in regulation of this level. Sixty subjects were included in this experiment, who were divided into 3 groups: group I (normal control), group II (MetS patients with normal liver enzymes), and group III (MetS with elevated liver enzymes and fatty liver disease). Serum irisin levels showed significant increases in groups II and III compared with group I, and significant increases in group III compared with group II. Also, irisin levels were positively correlated with body mass index, serum triglycerides, homeostatic model assessment of insulin resistance index (HOMA-IR), and liver enzymes. We concluded that serum irisin levels increased in patients with MetS, especially those with elevated liver enzymes, and had a positive correlation with parameters of lipid metabolism and glucose homeostasis with the possibility of hepatic clearance to irisin.

Lipoxin A4 attenuated dexamethasone-induced muscle atrophy via activation of PGC-1α/Nrf2/TFAM pathway.

Prolonged dexamethasone (DEX) administration causes skeletal muscle atrophy through induction of both oxidative stress and mitochondrial dysfunction. Lipoxin A4 (LXA4) is a recognized antioxidant but its effect against DEX-induced muscle atrophy has not been studied yet. This study aimed to assess the potential ameliorating effect of LXA4 on DEX-induced muscle atrophy and investigate the possible involvement of the mitochondrial dynamics pathway and the redox state in this effect. Forty male rats were divided into four groups; normal control, LXA4-treated, DEX-treated, and LXA4 plus DEX-treated. At the end of the experiment, LXA4 counteracted the effect of DEX on different parameters including muscle weight, muscle strength, serum creatine kinase activity, malondialdehyde and protein carbonyl contents, Na/K-ATPase and citrate synthase activities, mitochondrial transmembrane potential, mitochondrial transcription factor (TFAM), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and nuclear factor erythroid 2-related factor 2 (Nrf2). These findings signify the promising therapeutic effect of LXA4 against DEX-induced skeletal muscle atrophy and indicate the possible involvement of LXA4-induced mitochondrial activation in addition to its well-known antioxidant effects.

Possible mitigating effect of adropin on lung injury in diabetic rats: Targeting the role of Rho A/Rho-associated kinase pathway.

This study evaluated possible mitigating effect of adropin on lung injury in diabetic rats, targeting role of Rho A/Rho-associated kinase pathway. Rats were allocated into four groups: control, adropin, diabetic, and diabetic+adropin groups. At the termination of the experiment, serum fasting glucose, insulin and adropin levels and insulin resistance were calculated. Wet/dry ratio, histopathological, immunohistochemical analyses, and relative real time gene expression of lung tissue was determined. Interleukin-6, tumor necrosis factor alpha, malondialdehyde, 8-Oxo-2'-deoxyguanosine, reduced glutathione, superoxide dismutase, Bcl-2, BAX, myeloperoxidase, intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and transforming growth factor-ß were determined in lung tissue. Adropin treatment in diabetic rats notably attenuated hyperglycemia and insulin resistance. Also, it mitigated diabetic lung injury via suppressing effect on Rho A/ROCK pathway, apoptosis, inflammatory reactions, oxidative stress, and fibrosis of lung tissue. Adropin can be considered as a promising therapeutic agent for treating diabetic lung injury.

Fenofibrate Improves Cognitive Impairment Induced by High-Fat High-Fructose Diet: A Possible Role of Irisin and Heat Shock Proteins.

A high-fat, high-fructose diet (HFFD) impairs cognitive functions and increases susceptibility to neurodegenerative disorders. Irisin and heat shock protein 70 (HSP70) are well known for their role in neuroprotection. The possible neuroprotective effects of fenofibrate on HFFD-induced cognitive dysfunction and the involvement of irisin and HSP70 in these effects were investigated in this study. Rats were divided into normal control, HFFD, dimethylsulfoxide+HFFD, and fenofibrate+HFFD groups. At the end of the experiment, fenofibrate treatment restored hippocampus histological characteristics to almost normal and improved HFFD-induced cognitive deficit. It reduced body weight gain and had hypolipidemic effects by significantly lowering total cholesterol, triglycerides, and low-density lipoprotein cholesterol levels while increasing high-density lipoprotein cholesterol levels. It has antioxidant and anti-inflammatory effects as it significantly reduced the hippocampal malondialdehyde, interleukin-6, and tumor necrosis factor-alpha levels, while significantly increasing the reduced glutathione level. It prevented HFFD-induced hypoxia by significantly lowering hippocampal vascular endothelial growth factor and hypoxia-inducible factor-1 alpha levels. It significantly activated the hippocampal peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α)/irisin/brain-derived neurotrophic factor pathway. It significantly increased hippocampal HSP70 while decreasing the HSP90 levels. It enhanced synaptic plasticity by significantly upregulating the hippocampal relative GluR1 gene expression. Furthermore, hippocampal irisin levels in the HFFD group were found to be positively correlated with cognitive function, hippocampal HSP70, and relative GluR1 gene expression levels, while negatively correlated with hippocampal HSP90 and HIF1α levels. Therefore, fenofibrate may be used as a potential medication to treat HFFD-induced neurodegenerative disorders.

Fisetin ameliorates oxidative glutamate testicular toxicity in rats via central and peripheral mechanisms involving SIRT1 activation.

OBJECTIVES: This study aimed to evaluate the potential mitigating effect of fisetin on monosodium glutamate (MSG)-induced testicular toxicity and investigate the possible involvement of silent mating type information regulation 2 homolog 1 (SIRT1) in this effect. METHODS: Forty male rats were divided into normal control, fisetin-treated, MSG-treated, and fisetin + MSG-treated groups. Testosterone, GnRH, FSH, and LH were measured in plasma, as well as SIRT1 and phosphorylated AMP-activated protein kinase (pAMPK) levels in testicular tissues using ELISA. Hydrogen peroxide (H2O2), nitric oxide (NO), and reduced glutathione (GSH) were measured colorimetrically, while Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) expression was relatively quantified using RT-PCR in testicular tissues. RESULTS: After 30 days, fisetin could ameliorate MSG-induced testicular toxicity by acting centrally on the hypothalamic-pituitary-gonadal axis, increasing plasma levels of GnRH, FSH, LH, and testosterone. Peripheral actions of fisetin on the testis were indicated as it increased testicular SIRT1 and pAMPK. Furthermore, it antagonized glutamate-induced oxidative stress by significantly lowering H2O2, NO, and relative NOX4 expression while significantly increasing reduced GSH levels. It also improved the architecture of the seminiferous tubules, reduced sperm abnormality, and increased sperm count. DISCUSSION: Fisetin ameliorates MSG-induced testicular toxicity via central and peripheral mechanisms making it a promising therapeutic target for male infertility.

Metformin ameliorated methotrexate-induced hepatorenal toxicity in rats in addition to its antitumor activity: two birds with one stone.

Methotrexate (MTX) is a drug used in treatment of various malignancies. Unfortunately, it leads to life-threatening complications including hepatorenal toxicity. Previous studies revealed the protective effects of metformin (MET) on hepatorenal toxicity in other models in addition to its anticancer effects. The current study investigates the effect of MET on MTX-induced hepatorenal toxicity and the possible mechanisms involved in this toxicity which can be overwhelmed by MET. Thirty male rats were divided into 3 groups: normal control, MTX treated and MET/MTX treated. After 7 days, MTX induced hepatorenal toxicity as proved by histological examinations and biochemical analysis of liver and kidney functions. Also, it led to significant increase in hepatic and renal malondialdehyde levels, significant decrease in hepatic and renal total antioxidant capacity levels and Na+/K+-ATPase activities and significant up regulation of mRNA expressions of nuclear factor kappa-light-chain-enhancer of activated B cells, cyclooxygenase-2 and caspase 3 compared with the control group. While, MET could significantly reduce hepatorenal toxicity and counteract the effects of MTX on all measured parameters. In conclusion, MET can be an effective adjuvant to MTX chemotherapy that could ameliorate its hepatorenal toxicity through antioxidant, anti-inflammatory and anti-apoptotic mechanisms.

Efficacy and safety of sofosbuvir-ledipasvir for treatment of a cohort of Egyptian patients with chronic hepatitis C genotype 4 infection.

BACKGROUND AND AIMS: Treatment of hepatitis C virus (HCV) infection has significantly changed during the last few years. The combination of ledipasvir and sofosbuvir has been shown to treat high proportions of patients with HCV genotype 1 with remarkable tolerability. The aim of the work was to assess the efficacy and safety of sofosbuvir plus ledipasvir in treating treatment-naïve Egyptian patients with genotype 4 HCV infection. PATIENTS AND METHODS: In this open-label randomized study, 200 treatment-naive patients who were HCV antibody positive and HCV RNA positive by polymerase chain reaction, aged >18 years, were enrolled. The patients were classified into two groups: group I included 100 patients who received single therapy with sofosbuvir plus ledipasvir for 12 weeks and group II included 100 patients who received sofosbuvir plus oral weight-based ribavirin for 24 weeks. The primary end point was a sustained virological response at 12 weeks (SVR12) after the end of treatment, determined by quantitative polymerase chain reaction for HCV RNA. RESULTS: Group I patients showed statistically significant (p<0.05) higher SVR12 compared with group II patients (99% vs. 80%). There was no statistical difference (p>0.05%) between the studied groups regarding the frequencies of the side effects (26% vs. 29%). The most common adverse effects were headache, fatigue, myalgia, and cough. CONCLUSION: Sofosbuvir and ledipasvir treatment for 12 weeks was well tolerated by patients with HCV genotype 4 and resulted in 99% SVR for all patients who received 12 weeks of the study drugs. ClinicalTrials.gov Identifier: NCT02992457.

Randomized Controlled Study Comparing Use of Propofol Plus Fentanyl versus Midazolam Plus Fentanyl as Sedation in Diagnostic Endoscopy in Patients with Advanced Liver Disease.

OBJECTIVES: We aimed to investigate the safety and efficacy of propofol plus fentanyl versus midazolam plus fentanyl as sedative for patients with advanced liver disease presented for gastrointestinal endoscopy. METHODS: A total of 100 patients with liver cirrhosis referred for upper endoscopy were enrolled and divided equally in two groups, midazolam plus fentanyl group and propofol plus fentanyl group. All patients were subjected to history taking, estimation of level of sedation, endoscopist rating, and hemodynamic parameters including oxygen saturation, heart rate, mean arterial pressure, incidence of side effect as (bradycardia, hypotension, hypoxia, nausea and vomiting, cough, shivering, or diplopia), time needed for complete recovery, and time needed for discharge. RESULTS: There was no statistical significant difference between the studied groups regarding age, sex, weight, Child-Pugh classification score, type and duration of endoscopic intervention, time needed for complete recovery, or time needed for discharge. Complication rates were similar in both groups except for mean arterial blood pressure which was significantly lower in group of patients receiving propofol and fentanyl (P = 0.001). CONCLUSION: The use of either propofol or midazolam in combination to fentanyl is effective in sedation of patients with advanced liver diseases presented for upper GIT endoscope. The trial is registered with ClinicalTrials.gov Identifier: NCT03063866.