0000000000077364
AUTHOR
J Esplugues
Differential Effects of Biologics on Psoriasis-Related Vascular Inflammation and Risk of Thrombosis
Programa Estatal de I+D+i Orientada a los Retos de la Sociedad from Ministerio de Ciencia, Innovación y Universidades and European Regional Development Fund (Spain) [RTI2018-094436-B-I00]; Ministerio de Sanidad y Consumo CIBERehd (Spain) [CB06/04/0071]; Generalitat Valenciana (Spain) [PROMETEO/2018/141]; Proyectos Grupos Emergentes [GV/2019/043]; and Universidad Europea (Spain) (2018/UEM32 and 2019/UEM29]. 8.551 JCR (2020) Q1, 4/69 Dermatology 1.951 SJR (2020) Q1, 54/438 Biochemistry No data IDR 2020 UEV
Differential Effects of Verapamil on Various Gastric Lesions in Rats
Verapamil (3, 10, 20 mg/kg-1) increases the necrotizing effects of oral 25% NaCl or 100% ethanol. Damage by 0.6 N HCl was not equally affected since 1 mg/kg-1 of verapamil decreased the ulcer index whereas the higher doses augmented it. Pharmacologically induced gastric lesions were also differently affected by verapamil, ulcers produced by histamine being greatly enhanced and those of reserpine inhibited. Neither indomethacin nor compound 48/80 ulcers were modified. These results suggest that verapamil modifies the susceptibility of the gastric mucosa to damage.
Rilpivirine attenuates liver fibrosis through selective STAT1-mediated apoptosis in hepatic stellate cells
ObjectiveLiver fibrosis constitutes a major health problem worldwide due to its rapidly increasing prevalence and the lack of specific and effective treatments. Growing evidence suggests that signalling through cytokine-activated Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathways regulates liver fibrosis and regeneration. Rilpivirine (RPV) is a widely used anti-HIV drug not reported to produce hepatotoxicity. We aimed to describe the potential hepatoprotective effects of RPV in different models of chronic liver injury, focusing on JAK-STAT signalling regulation.DesignThe effects of RPV on hepatic steatosis, inflammation and fibrogenesis were studied in a nut…
Apoptosis of Hepatocytes: Relevance for HIV-Infected Patients under Treatment.
Due to medical advances over the past few decades, human immunodeficiency virus (HIV) infection, once a devastatingly mortal pandemic, has become a manageable chronic condition. However, available antiretroviral treatments (cART) cannot fully restore immune health and, consequently, a number of inflammation-associated and/or immunodeficiency complications have manifested themselves in treated HIV-infected patients. Among these chronic, non-AIDS (acquired immune deficiency syndrome)-related conditions, liver disease is one of the deadliest, proving to be fatal for 15–17% of these individuals. Aside from the presence of liver-related comorbidities, including metabolic disturbances and co-infe…
Effects of calcium channel blockers on gastric emptying and acid secretion of the rat in vivo.
Abstract Experiments were designed to evaluate the effects of three calcium channel blockers (verapamil, diltiazem and cinnarizine) on gastric emptying and secretion in the rat. Pretreatment with the calcium blockers delayed gastric emptying of phenol red in a dose-dependent manner. Verapamil was the most effective of the agents tested. Verapamil and diltiazem inhibited gastric acid secretion in the pylorus-ligated rat without affecting pepsin output. Cinnarizine was ineffective in this model. When the perfused lumen of the anaesthetized rat was used, verapamil was found to inhibit responses to carbachol or histamine more than those to pentagastrin. Further, we found a greater sensitivity t…
Protection by Almagate of Ethanol-induced Gastric Mucosal Damage in Rats
Abstract The study was designed to analyse the protective effects of almagate on a model of gastric injury, ethanol-induced mucosal damage, in which acid plays little, if any, role. Pretreatment with almagate dose-dependently reduced the level of gastric damage induced by oral administration of 1mL 100% ethanol. Administration of 12 μmol kg−1 almagate 30 min before ethanol significantly reduced the area of mucosal damage by 65 ± 10%, and the maximum level of inhibition (74 ± 11%) was obtained with 150 μmol kg−1 almagate. Administration of higher doses of almagate (200–250 μmol kg−1) did not result in any further increase in the level of protection against ethanol-induced gastric damage. Adm…
Effects of zinc acexamate on blood flow and prostanoid levels in the gastric mucosa of the rat
The effects of the new antiulcer compound zinc acexamate on blood flow and prostanoid levels in the gastric mucosa have been studied. Zinc acexamate (30 and 300 mg/kg) dose-dependently prevents the reduction induced by the perfusion of noradrenaline (3.5 micrograms/kg.min, 30 min) in gastric mucosal blood flow, as measured by 3H-aniline clearance. Zinc acexamate pretreatment also increases the levels of prostaglandin E2 in the gastric mucosa of the rat, both under control conditions and after infusion with noradrenaline. The levels of thromboxane A2 and prostacyclin were not modified by zinc acexamate. These results confirm the importance of microcirculation in pathogenesis and the idea tha…
Role of p62/SQSTM1 beyond autophagy: a lesson learned from drug-induced toxicity in vitro
Background and Purpose SQSTM1/p62 is a multifunctional, stress-induced, scaffold protein involved in multiple cellular processes including autophagic clearance, regulation of inflammatory responses and redox homeostasis. Its altered function has been associated with different human pathologies, such as neurodegenerative, metabolic and bone diseases (down-regulation), and cancerogenesis (up-regulation). However, its role in the off-target effects of clinically used drugs is still not understood. Experimental Approach We evaluated the expression of p62 in cultured Hep3B cells and their derived ρ° cells (lacking mitochondria), along with markers of autophagy and mitochondrial dysfunction. The …
Influence of capsaicin-sensitive afferent neurones on the acid secretory responses of the rat stomach in vivo.
1. The influence of capsaicin-sensitive afferent neurones in modulating acid-secretory responses has been investigated in the continuously perfused stomach of the anaesthetized rat. 2. Ablation of primary afferent neurones, after systemic neonatal pretreatment with high doses of capsaicin, did not modify acid responses to direct stimuli of the oxyntic cell with histamine (5 mg kg-1), pentagastrin (20 micrograms kg-1) or carbachol (4 micrograms kg-1). 3. Acid responses to hypoglycaemia induced by insulin (0.3 iu kg-1) were not influenced by systemic capsaicin pretreatment or by acute coeliac ganglionectomy. Vagotomy abolished this secretory response. 4. The increase in acid output induced by…
Modulation by peripheral opioids of basal and distension-stimulated gastric acid secretion in the rat.
1. The influence of opioids in modulating gastric acid secretory responses has been investigated in the continuously perfused stomach of the anaesthetized rat. 2. Intravenous administration of morphine (0.75-3 mg kg-1) or the peripherally acting enkephalin analogue, BW443C (0.75-3 mg kg-1), substantially augmented acid secretion in basal conditions. These effects were significantly inhibited by the opioid antagonists naloxone (1 mg kg-1) and the peripherally acting N-methylnalorphine (2 mg kg-1). When administered alone, neither opioid antagonist influenced basal acid output. 3. Acid secretory responses to different levels of gastric distension (5-20 cmH2O) were significantly and dose-depen…
Lon protease: a novel mitochondrial matrix protein in the interconnection between drug-induced mitochondrial dysfunction and endoplasmic reticulum stress
Background and Purpose Mitochondria-associated membranes (MAMs) are specific endoplasmic reticulum (ER) domains that enable it to interact directly with mitochondria and mediate metabolic flow and Ca2+ transfer. A growing list of proteins have been identified as MAMs components, but how they are recruited and function during complex cell stress situations is still not understood, while the participation of mitochondrial matrix proteins is largely unrecognized. Experimental Approach This work compares mitochondrial/ER contact during combined ER stress/mitochondrial dysfunction using a model of human hepatoma cells (Hep3B cell line) treated for 24 h with classic pharmacological inducers of ER…
Effect of verapamil and diltiazem on isolated gastro-oesophageal sphincter of the rat
Abstract The effect of verapamil and diltiazem on the contraction induced by agonists on the rat lower oesophageal sphincter in-vitro has been studied. Both calcium entry blockers inhibited the contractile response to acetylcholine, carbachol and KCl. The potency of the inhibitory action was diltiazem > verapamil. The results give substance to the use of calcium entry blockers in the treatment of oesophageal spasm.
Zinc acexamate inhibits gastric acid and pepsinogen secretion in the rat.
Abstract Pretreatment with zinc acexamate (25–100 mg kg−1 i.p.) inhibited acid and pepsinogen secretion in the pylorus-ligated rat. Zinc acexamate (5–50 mg kg−1 p.o.) also inhibited the increases in acid secretion induced by carbachol (10 μg kg−1) and 2-deoxy-D-glucose (200 mg kg−1) in the perfused stomach of the anaesthetized rat. A delayed antisecretory effect was observed with this drug on histamine induced responses. High concentrations of zinc acexamate (10−5-10−2 M) did not modify the in-vitro activity of pepsin. Administration of zinc acexamate resulted in an increase in the presence of pepsinogen at the mucosal level. A morphological examination of the gastric mucosa confirmed an ac…