Hepatic angiotensin

BACKGROUND: Methotrexate (MTX) is a folic acid antagonist, commonly administered for the treatment of a variety of cancers. However, methotrexate toxicity including bone marrow suppression and hepatic and renal toxicity limits its use. Angiotensin AT1 receptor blockers including Valsartan (Val) possess the ability to ameliorate MTX-induced toxicity through various mechanisms. In this study, we explored the potential reno-protective effects of Val against MTX-induced acute kidney injury in rats...

This review navigates the intricate relationship between gender, hormonal influences, and the progression of autosomal dominant polycystic kidney disease (ADPKD), highlighting the limited literature on this crucial topic. The study explores the impact of female sex hormones on liver and renal manifestations, uncovering gender-specific differences in disease progression. Actually, hormonal therapy in women with ADPKD remains a challenging issue and is a source of concern regarding its potential impact on disease outcomes, particularly at the hepatic level...

AGT (angiotensinogen) is the unique precursor for the generation of all the peptides of the renin-angiotensin system, but it has received relatively scant attention compared to many other renin-angiotensin system components. Focus on AGT has increased recently, particularly with the evolution of drugs to target the synthesis of the protein. AGT is a noninhibitory serpin that has several conserved domains in addition to the angiotensin II sequences at the N terminus. Increased study is needed on the structure-function relationship to resolve many unknowns regarding AGT metabolism...

BACKGROUND: Cardiovascular diseases (CVDs) continue to exert a substantial global influence in specific areas due to population growth, aging, microbiota, and genetic/environmental factors. Drinking water has a strong impact on the health of an individual. Further, emerging evidence has highlighted the therapeutic potential and benefits of Zamzam water (Zam). OBJECTIVE: We investigated the influence of Zam on doxorubicin-induced cardiac toxicity, elucidating its consequential effects on GUT microbiota dysbiosis and hepatic and renal functions...

BACKGROUND: SLCO1B1 plays an important role in mediating hepatic clearance of many different drugs including statins, angiotensin-converting enzyme inhibitors, chemotherapeutic agents and antibiotics. Several variants in SLCO1B1 have been shown to have a clinically significant impact, in relation to efficacy of these medications. This study provides a comprehensive overview of SLCO1B1 variation in Saudi individuals, one of the largest Arab populations in the Middle East. METHODS: The dataset of 11,889 (9,961 exomes and 1,928 pharmacogenetic gene panel) Saudi nationals, was used to determine the presence and frequencies of SLCO1B1 variants, as described by the Clinical Pharmacogenetic Implementation Consortium (CPIC)...

OBJECTIVE: Sepsis-associated liver injury is responsible for the high morbidity and mortality rates seen with septic shock. Activation of the renin-angiotensin-aldosterone system (RAAS) is an essential counteractive mechanism during the hypotensive phase of sepsis; however, excessive activation is associated with exaggerated pro-oxidant and inflammatory response, which aggravates organ damage. This study aimed to evaluate the effect of RAAS inhibition on sepsis-induced liver damage. MATERIALS AND METHODS: The cecal ligation and puncture (CLP) model was employed as a model of sepsis...

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The present letter to the editor is related to the study titled ' Angiotensin-converting enzyme 2 improves liver fibrosis in mice by regulating autophagy of hepatic stellate cells'. Angiotensin-converting enzyme 2 can alleviate liver fibrosis by regulating autophagy of hepatic stellate cells and affecting the renin-angiotensin system.

BACKGROUND AND AIMS: Obesity increases the risk for abdominal aortic aneurysms (AAA) in humans and enhances angiotensin II (AngII)-induced AAA formation in C57BL/6 mice. We reported that deficiency of Serum Amyloid A (SAA) significantly reduces AngII-induced inflammation and AAA in both hyperlipidemic apoE-deficient and obese C57BL/6 mice. The aim of this study is to investigate whether SAA plays a role in the progression of early AAA in obese C57BL/6 mice. METHODS: Male C57BL/6J mice were fed a high-fat diet (60% kcal as fat) throughout the study...

To control hypertension, long-term continuous antihypertensive therapeutics are required and five classes of antihypertensive drugs are frequently involved, including diuretics, β-blockers, calcium channel blockers, angiotensin II receptor blockers, and angiotensin-converting enzyme inhibitors. Although with demonstrated clinical utility, there is still room for the improvement of many antihypertensive drugs in oral tablet or capsule dosage form, in terms of reducing systemic side effects and first-pass hepatic drug uptake...

The lipid-based drug delivery system (LBDDS) is a well-established technique that is anticipated to bring about comprehensive transformations in the pharmaceutical field, impacting the management and administration of drugs, as well as treatment and diagnosis. Various LBDDSs verified to be an efficacious mechanism for monitoring hypertension systems are SEDDS (self-nano emulsifying drug delivery), nanoemulsion, microemulsions, vesicular systems (transferosomes and liposomes), and solid lipid nanoparticles. LBDDSs overcome the shortcomings that are associated with antihypertensive agents because around fifty percent of the antihypertensive agents experience a few drawbacks including short half-life because of hepatic first-pass metabolism, poor aqueous solubility, low permeation rate, and undesirable side effects...

The emergence and mutation of pathogenic viruses have been occurring at an unprecedented rate in recent decades. The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed into a global public health crisis due to extensive viral transmission. In situ RNA mapping has revealed angiotensin-converting enzyme 2 (ACE2) expression to be highest in the nose and lower in the lung, pointing to nasal susceptibility as a predominant route for infection and the cause of subsequent pulmonary effects...

OBJECTIVES: Midodrine, an oral α-1-adrenergic receptor agonist, counters arterial hypovolemia and reduces complications in adult patients with cirrhosis. This randomized controlled trial (RCT) aimed to assess the efficacy and safety of midodrine in preventing complications and improving survival in children with cirrhosis and ascites who are awaiting liver transplantation (LT). METHODS: This open-label RCT conducted from January 2022 to May 2023 included children under 18 years with cirrhosis and ascites...

IMPORTANCE: Angiotensinogen is the most upstream precursor of the renin-angiotensin-aldosterone system, a key pathway in blood pressure (BP) regulation. Zilebesiran, an investigational RNA interference therapeutic, targets hepatic angiotensinogen synthesis. OBJECTIVE: To evaluate antihypertensive efficacy and safety of different zilebesiran dosing regimens. DESIGN, SETTING, AND PARTICIPANTS: This phase 2, randomized, double-blind, dose-ranging study of zilebesiran vs placebo was performed at 78 sites across 4 countries...

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes multi-organ damage, which includes hepatic dysfunction, as observed in over 50% of COVID-19 patients. Angiotensin I converting enzyme (peptidyl-dipeptidase A) 2 (ACE2) is the primary receptor for SARS-CoV-2 entry into host cells, and studies have shown the presence of intracellular virus particles in human hepatocytes that express ACE2, but at extremely low levels. Consequently, we asked if hepatocytes might express receptors other than ACE2 capable of promoting the entry of SARS-CoV-2 into cells...

Glycyrrhizic acid (GA), one of the major active components derived from licorice root, exerts liver-protecting activity. Its molecular mechanisms of action, however, remain not completely understood. The angiotensin (Ang) converting enzyme (ACE) 2/Ang-(1-7)/Mas axis, regulated by ACE2 through converting Ang II into Ang-(1-7) to activate Mas receptor, counteracts the pro-inflammatory and pro-steatotic effects of the ACE/Ang II/Ang II receptor type 1 (AT1) axis. Here, it was found that pretreatment with GA suppressed LPS/D-galactosamine-induced serum hyperactivities of alanine aminotransferase and aspartate aminotransferase, hepatomegaly, pathological changes, and over-accumulation of triglycerides and fatty droplets in the liver of mice...

In coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) primarily targets the respiratory system, but evidence suggests extrapulmonary organ involvement, notably in the liver. Viral RNA has been detected in hepatic tissues, and in situ hybridization revealed virions in blood vessels and endothelial cells. Electron microscopy confirmed viral particles in hepatocytes, emphasizing the need for understanding hepatotropism and direct cytopathic effects in COVID-19-related liver injury...

The effects of coronavirus disease 2019 (COVID-19) primarily concern the respiratory tract and lungs; however, studies have shown that all organs are susceptible to infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 may involve multiorgan damage from direct viral invasion through angiotensin-converting enzyme 2 (ACE2), through inflammatory cytokine storms, or through other secondary pathways. This study involved the analysis of publicly accessible transcriptome data from the Gene Expression Omnibus (GEO) database for identifying significant differentially expressed genes related to COVID-19 and an investigation relating to the pathways associated with mitochondrial, cardiac, hepatic, and renal toxicity in COVID-19...

OBJECTIVE: Metformin (MET) is a drug used in the treatment of type 2 diabetes due to its insulin receptor sensitizing properties and anti-hepatic gluconeogenesis effect. One of the comorbidities in diabetes is the depression. This review aimed at summarizing the results of the available MET, depression and diabetes studies to clarify the possible role of MET in the depression during diabetes. METHODS: A bibliographic search on PubMed, Embase, PsycINFO, Web of Science, Cochrane Central for studies referring to MET, depression and diabetes...

AIM: Hepatic fibrosis, a progressive scarring of liver tissue, is commonly caused by non-alcoholic fatty liver disease (NAFLD), which increases the risk of cardiovascular disease. The Fibrosis-4 (FIB-4) index is a non-invasive tool used to assess liver fibrosis in patients with NAFLD. Aortic valve sclerosis (AVS), a degenerative disorder characterized by thickening and calcification of valve leaflets, is prevalent in the elderly and associated with increased cardiovascular morbidity and mortality...