One-pot synthesis and pharmacological evaluation of new quinoline/pyrimido-diazepines as pulmonary antifibrotic agents.

Pulmonary fibrosis is a life threating disease which requires an immediate treatment and due to the limited medications, this study focused on synthesizing a series of quinoline-based pyrimidodiazepines as a novel antifibrotic hit. The target compounds were synthesized via a one-pot reaction then investigated in a rat model of lung fibrosis induced by bleomycin (BLM). Results revealed significant attenuation of the tested pro-inflammatory cytokines, fibrotic genes and apoptotic markers; however, Bcl-2 was upregulated, indicating a protective effect against fibrosis.

The ameliorative effect of vinpocetine against gentamicin-induced uterine-injury in rats involves the inflammasome/caspase-1/IL-1β pathway.

Background: There is limited data regarding the hazardous effect of gentamicin (GM) on the uterus and whether or not vinpocetine (Vinpo) ameliorates it. The present study aimed to identify the possible protective effect of Vinpo in GM-induced uterine injury in rats.

Methods: Female rats were assorted in control-group, Vinpo-group, GM-group, and Vinpo plus GM group.

Molecular mechanism of empagliflozin cardioprotection in 5-fluorouracil (5-FU)-induced cardiotoxicity via modulation of SGLT2 and TNFα/TLR/NF-κB signaling pathway in rats.

Unlabelled: One of the commoly used chemotherapeutic agents is 5-Fluorouracil (5-FU). Unfortunately, the clinical administration of 5-FU is complicated with serious cardiotoxic effects and the safe use becomes an urgent task in cardio-oncology. Till now, there are no studies discussed the role of empagliflozin (EMP) against 5-FU cardiotoxicity.

Curative Effect of AD-MSCs against Cisplatin-Induced Hepatotoxicity in Rats is Potentiated by Azilsartan: Targeting Oxidative Stress, MAPK, and Apoptosis Signaling Pathways.

Despite its clinical value, cisplatin (CISP) is complicated by marked hepatotoxicity via inducing oxidative stress, inflammatory, and apoptotic pathways. This study aims to explore the protective impact of azilsartan (AZIL), an antihypertensive drug, in addition to adipose tissue-derived mesenchymal stem cells (AD-MSCs) on CISP-induced hepatotoxicity. After characterization and labeling of AD-MSCs by PKH26 dye, 54 Wistar male albino rats were randomly divided into nine groups: I (CONT), II (AZIL.

Molecular mechanisms mediate roflumilast protective effect against isoprenaline-induced myocardial injury.

Background: Myocardial necrosis is one of the most common cardiac and pathological diseases. Unfortunately, using the available medical treatment is not sufficient to rescue the myocardium. So that, we aimed in our model to study the possible cardioprotective effect of roflumilast (ROF) in an experimental model of induced myocardial injury using a toxic dose of isoprenaline (ISO) and detecting the role of vascular endothelial growth factor/endothelial nitric oxide synthase (VEGF/eNOS) and cyclic guanosine monophosphate/cyclic adenosine monophosphate/ sirtuin1 (cGMP/cAMP/SIRT1) signaling cascade.

Diacerein modulates TLR4/ NF-κB/IL-1β and TRPC1/CHOP signalling pathways in gentamicin-induced parotid toxicity in rats.

The present study aimed to identify the possible protective effect of diacerein (DIA) on gentamicin (GNT)-induced parotid toxicity in rats. DIA was administered in the presence and absence of GNT. Thirty-two Wistar adult male rats were randomly arranged into four groups: control, DIA (50 mg/kg/day), GNT (100 mg/kg) and GNT+DIA groups for 8 days.

Protective effect of eicosapentaenoic acid against estradiol valerate-induced endometrial hyperplasia via modulation of NF-κB/HIF-1α/VEGF signaling pathway in rats.

Background: Early diagnosis and treatment of endometrial hyperplasia (EH) remains mandatory for endometrial cancer (EC) prevention.

Objective: To study the possible protective effect of eicosapentaenoic acid (EPA) in EH - induced by estradiol valerate (EV) in rats.

Methods/materials: Adult female Wistar rats were given EV with or without EPA for 10 days.

In Vitro Anticancer Activity of Novel Ciprofloxacin Mannich Base in Lung Adenocarcinoma and High-Grade Serous Ovarian Cancer Cell Lines via Attenuating MAPK Signaling Pathway.

Novel drugs are desperately needed in order to combat a significant challenge due to chemo-therapeutic resistance and bad prognosis. This research aimed to assess the anticancer activity of a newly synthesized ciprofloxacin Mannich base (CMB) on ovarian cancer (OVCAR-3) and lung cancer (A-549) cell lines and to investigate probable involved molecular mechanisms. The cytotoxic and pro-apoptotic impact of CMB on both cell lines was investigated using MTT assay, Annexin V assay, and cell cycle analysis, as well as caspase-3 activation.

The IL-6/HO-1/STAT3 signaling pathway is implicated in the amelioration of acetaminophen-induced hepatic toxicity: A neonatal rat model.

The widespread use of acetaminophen (APAP) in children as an over-the-counter treatment can cause acute liver failure through accidental overdose or ingestion. Therefore, the current research sought to investigate the function of hemin in mitigating the acute hepatotoxic effect of APAP in rat offspring. Thirty-two rats were assigned into four groups: control, hemin, APAP, and hemin/APAP groups.

Quercetin potentiates the hepatoprotective effect of sildenafil and/or pentoxifylline against intrahepatic cholestasis: Role of Nrf2/ARE, TLR4/NF-κB, and NLRP3/IL-1β signaling pathways.

Aim: Intrahepatic cholestasis is a common pathological condition of several types of liver disorders. In this study, we aimed to investigate the regulatory effects of quercetin (QU) on selected phosphodiesterase inhibitors against alpha-naphthyl isothiocyanate (ANIT)-induced acute intrahepatic cholestasis.

Methods: Cholestasis was induced in Wistar albino rats by ANIT as a single dose (60 mg/kg; P·O.

Nephroprotective effect of AT-MSCs against cisplatin-induced EMT is improved by azilsartan via attenuating oxidative stress and TGF-β/Smad signaling.

The nephrotoxicity of cisplatin (CIS) is a significant complication that challenges its clinical applicability. The epithelial to mesenchymal transition (EMT) may be included in the pathogenesis of CIS-evoked nephrotoxicity. Therefore, the current study aimed to evaluate, for the first time, the possible protective effect of AZL and/or AT-MSCs against CIS-induced EMT in rats on molecular bases.

Phosphodiesterase inhibitor, Vinpocetine, guards against doxorubicin induced cardiotoxicity modulation of HIF/VEGF and cGMP/cAMP/SIRT signaling pathways.

Methods: 50 male Wistar albino rats were subjected to DOX toxicity via administration of single Dose (15 mg/kg) on the 4th day with or without co-administration of VIN (10, 20, 30 mg/kg/day) orally for 5 days.

Results: Our data revealed that VIN succeeded in protecting the heart against DOX induced damage as manifested by significant decrease of cardiac enzymes, hypoxia inducible factor alpha (HIF-1α), vascular endothelial growth factor-A (VEGF-A), tissue malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α) and caspase3 levels. Furthermore, VIN given group showed marked improvement of the histopathological changes of cardiac injury, total antioxidant capacity (TAC), elevation of reduced glutathione (GSH), cyclic guanosine monophosphate (cGMP), cyclic adenosine monophosphate (cAMP) and sirtuin-1 (SIRT-1).

Dapagliflozin Guards Against Cadmium-Induced Cardiotoxicity via Modulation of IL6/STAT3 and TLR2/TNFα Signaling Pathways.

Cadmium (Cd) is a common environmental pollutant that leads to severe cardiotoxic hazards. Several studies were carried out to protect the myocardium against Cd-induced cardiotoxicity. Up till now, no researches evaluated the protective effect of dapagliflozin (DAP) against Cd induced cardiotoxicity.

Idebenone regulates sirt1/Nrf2/TNF-α pathway with inhibition of oxidative stress, inflammation, and apoptosis in testicular torsion/detorsion in juvenile rats.

Testicular torsion is an emergency, mainly in newborn and adolescent males, resulting in testicular ischemia. The current study aimed to evaluate the effect of Idebenone (IDE) on testicular torsion/detorsion (T/D) in juvenile rats. Thirty-two rats were randomized into: (1) the sham group: rats received sham operations with no other interventions; (2) the IDE group: rats received idebenone (100 mg/kg, i.

Vincamine Modulates the Effect of Pantoprazole in Renal Ischemia/Reperfusion Injury by Attenuating MAPK and Apoptosis Signaling Pathways.

Pantoprazole has an antioxidant function against reactive oxygen species (ROS). Vincamine, a herbal candidate, is an indole alkaloid of clinical use against brain sclerosis. The aim of the present experiment is to evaluate, on a molecular level for the first time, the value of vincamine in addition to pantoprazole in treating experimentally induced renal ischemia/reperfusion injury (IRI).

Role of JNK, ERK, and p38 MAPK signaling pathway in protective effect of sildenafil in cyclophosphamide-induced placental injury in rats.

Aims: Chemotherapeutic agents; cyclophosphamide (CYC) is used for treatment of cancer and autoimmune diseases. Grievously, CYC is non-selective as it affects both tumor and healthy cells resulting in systemic toxicity including placenta. The present study aimed to evaluate the effect of phosphodiesterase 5 inhibitor, sildenafil (Sild) on CYC-induced placental injury in rats.

Pantoprazole Attenuates MAPK (ERK1/2, JNK, p38)-NF-κB and Apoptosis Signaling Pathways after Renal Ischemia/Reperfusion Injury in Rats.

Ischemia/reperfusion injury (IRI) in the kidney is the most common cause of acute renal dysfunction through different cell damage mechanisms. This study aimed to investigate, on molecular basics for the first time, the effect of pantoprazole on renal IRI in rats. Different biochemical parameters and oxidative stress markers were assessed.

A Role in the Genetic Predisposition to NAFLD-HCC?

Obesity and non-alcoholic fatty liver disease (NAFLD) are contributing to the global rise in deaths from hepatocellular carcinoma (HCC). The pathogenesis of NAFLD-HCC is not well understood. The severity of hepatic steatosis, steatohepatitis and fibrosis are key pathogenic mechanisms, but animal studies suggest altered immune responses are also involved.

LC-MS-based identification of bioactive compounds and hepatoprotective and nephroprotective activities of leaves against carbon tetrachloride-induced injury in rats.

The chemical profiling of the main phytoconstituents of total ethanolic extract (TEE) and its different fractions of leaves was dereplicated using liquid chromatography-high resolution-electrospray ionisation-mass spectrometry (LC-HR-ESI-MS), revealed the presence of various classes of secondary metabolites; eight phenylethanoids, two flavonoidal glycosides and two iridoids. Moreover, the hepatoprotective and nephroprotective activities of the TEE and its different fractions were investigated in carbon tetrachloride (CCl)-intoxicated rats and were compared with those of silymarin-treated group, revealing the highest potency of the EtOAc group, followed by the aqueous one in improving the CCl-induced alterations in several biochemical parameters. Besides, EtOAc and aqueous fractions exhibited the most inhibition of CCl-induced inflammatory mediators and improving the changes in the histopathological structures of the liver and kidney.

Impact of interleukin IL-6 rs-1474347 and IL-10 rs-1800896 genetic polymorphisms on the susceptibility of HCV-infected Egyptian patients to hepatocellular carcinoma.

Hepatitis C virus (HCV) is considered leading cause of cirrhosis and hepatocellular carcinoma (HCC). We aimed to examine the association of IL-6 and IL-10 single-nucleotide polymorphisms with the progression of chronic HCV (CHC) infection to cirrhosis and HCC. For comparative purposes, four groups were enrolled; chronic HCV group (CHC, n = 22), HCV-related liver cirrhosis group (HCV-LC, n = 22), HCV-related HCC group (HCV-HCC, n = 54), and an apparently healthy control group (controls, n = 48).

Antioxidant, anti-inflammatory and anti-fibrotic effects of gum resin in CCl-induced hepatotoxicity.

The present study aims to investigate the potential antioxidant, anti-inflammatory and anti-fibrotic effects of Boswellia serrate (BS) gum resin against carbon tetrachloride (CCl)-induced liver damage. Four groups consisting of eight rats each were designated: Group I, normal healthy control; group II, CCl-induced liver fibrosis; group III, CCl-induced liver fibrosis followed by BS treatment daily for two weeks; and group IV, CCl-induced liver fibrosis followed by silymarin treatment daily for two weeks. Expression of tumor necrosis factor-α (TNF-α) and nuclear factor κB (NF-κB), interleukin-6 (IL-6), transforming growth factor-β (TGF-β) and cyclooxygenase-2 (COX-2) were assessed, in addition to histopathological and fibrotic changes in liver tissues isolated from the rats.

Metabolomic profiling and biological investigation of (Silva Manso) leaves, family Bignoniaceae.

Both ethyl acetate and aqueous fractions of leaves exhibited noteworthy antioxidant and nephroprotective activities against carbon tetrachloride (CCl)-induced nephrotoxicity in rats, as evidenced by the remarkable improvements of renal serum biomarkers and histopathological features. Additionally, the ethyl acetate fraction displayed a prominent antitrypanosomal activity against ; consequently, the leaves were subjected to LC-HR-ESI-MS metabolomic profiling to discover the constituents that possibly underlie their bioactivities. Therefore, ten metabolites were characterized, mostly dominated by flavonoids.

Eugenol Exerts Apoptotic Effect and Modulates the Sensitivity of HeLa Cells to Cisplatin and Radiation.

Eugenol is a phytochemical present in different plant products, e.g., clove oil.

Modulation of inducible nitric oxide synthase pathway by eugenol and telmisartan in carbon tetrachloride-induced liver injury in rats.

Aims: Inducible nitric oxide synthase (iNOS) pathway has been in the limelight since its discovery as a key mediator in the process of liver fibrogenesis. Therefore, the objective of the current study was to elucidate the in vivo molecular mechanism underlying the hepatic preventive relevance of eugenol (EUG) and telmisartan (TEL) through iNOS pathway modulation against carbon tetrachloride (CCl4)-induced hepatic injury.

Methods: Sixty healthy male albino rats were used in this study.