Irbesartan Treatment Research Articles

Effect of Atorvastatin combined with Irbesartan in the treatment of early diabetic nephropathy.

To explore the effect of Atorvastatin combined with Irbesartan in the treatment of early diabetic nephropathy (DN). Clinical data from 153 patients with early DN, admitted to Huzhou Central Hospital from January 2020 to December 2022, was retrospectively selected. Patients were divided into two groups based on the treatment they received: patients received Irbesartan treatment alone were assigned to Irbesartan group (n=74); patients received Irbesartan combined with Atorvastatin were assigned to combined group (n=79). Levels of renal function indicators, renal fibrosis indicators, micro inflammatory status indicators, and incidence of adverse reactions were compared between the two groups before and after the treatment. After the treatment, indicators of renal function, renal fibrosis and micro-inflammation in both groups significantly decreased compared to pretreatment levels (P<0.05), and were significantly lower in the combined group compared to Irbesartan group (P<0.05). There was no significant difference in the incidence of adverse reactions between the groups (P>0.05). Compared with Irbesartan alone, Atorvastatin combined with Irbesartan is more effective in the treatment of early DN. Combined treatment regimen is able to effectively reduces the micro-inflammatory state, improve renal function and fibrosis, and is not associated with the increased risk of adverse reactions.

Effects of xenogeneic transplantation of umbilical cord-derived mesenchymal stem cells combined with irbesartan on renal podocyte damage in diabetic rats

BackgroundThe leading cause of end-stage renal disease (ESRD) is diabetic nephropathy (DN). Podocyte damage is an early event in the development of DN. Currently, there is no effective treatment strategy that can slow the progression of DN or reverse its onset. The role of mesenchymal stem cells (MSCs) transplantation in diabetes and its complications has been extensively studied, and diabetic nephropathy has been a major focus. Irbesartan exerts reno-protective effects independent of lowering blood pressure, can reduce the incidence of proteinuria in rats, and is widely used clinically. However, it remains undetermined whether the combined utilization of the angiotensin II receptor antagonist irbesartan and MSCs could enhance efficacy in addressing DN.MethodsA commonly used method for modeling type 2 diabetic nephropathy (T2DN) was established using a high-fat diet and a single low-dose injection of STZ (35 mg/kg). The animals were divided into the following 5 groups: (1) the control group (CON), (2) the diabetic nephropathy group (DN), (3) the mesenchymal stem cells treatment group (MSCs), (4) the irbesartan treatment group (Irb), and (5) the combined administration group (MSC + Irb). MSCs (2 × 106 cells/rat) were injected every 10 days through the tail vein for a total of three injections; irbesartan (30 mg/kg/d) was administered by gavage. Additionally, the safety and homing of mesenchymal stem cells were verified using positron emission tomography (PET) imaging.ResultsThe combination treatment significantly reduced the UACR, kidney index, IGPTT, HOMA-IR, BUN, serum creatine, and related inflammatory factor levels and significantly improved renal function parameters and the expression of proteins related to glomerular podocyte injury in rats. Moreover, MSCs can homing target to damaged kidneys.ConclusionsCompared to the administration of MSCs or irbesartan alone, the combination of MSCs and irbesartan exerted better protective effects on glomerular podocyte injury, providing new ideas for the clinical application of mesenchymal stem cells.

Percarbonate mediated advanced oxidation of irbesartan: A suitable alternative to chlorination?

This study aims to investigate the environmental fate of irbesartan when subjected to activated percarbonate treatment. The investigation delves into the formation of disinfection byproducts (DBPs) and evaluates their toxicity, and it seeks to draw comparisons with outcomes from treatment with sodium hypochlorite, already characterized in previous findings. The proposed treatment indicates the formation of at least 11 DBPs - eight identified for the first time - which have been isolated by various chromatographic techniques, identified by Nuclear Magnetic Resonance and Mass Spectrometry studies and for which a mechanism has been proposed to elucidate their formation. To evaluate irbesartan's biological impact during treatment with sodium percarbonate (SPC), a toxicity study of the DBPs was conducted using Daphnia magna, Aliivibrio fischeri, and Raphidocelis subcapitata, three model organisms. The ecotoxicity was evaluated using the Ecological Structure-Activity Relationships (ECOSAR) computer program and compared with experimental results. Compared to chlorination treatment, a lower mineralization percentage (−43 %) and amount of DBPs at least twice higher were observed. Toxicity assessment highlighted that DBPs formed during SPC treatment were more toxic than those from chlorination. ECOSAR predicted toxicity aligned with experimental findings. Additionally, the DBPs exhibited varying levels of toxicity, primarily attributable to the presence of aromatic and hydroxyl groups in their chemical structure, indicating that SPC treatment is not suitable for treatment of irbesartan polluted waters.

Irbesartan ameliorates diabetic kidney injury in db/db mice by restoring circadian rhythm and cell cycle.

Irbesartan has been widely used in the clinical treatment of diabetic kidney disease (DKD). However, the molecular mechanism of its delay of DKD disease progression has not been fully elucidated. The aim of the present study was to investigate the mechanism of irbesartan in the treatment of DKD. C57BL/KsJ db/db mice were randomly divided into the model group and irbesartan-treated group. After treatment with irbesartan for 12 weeks, the effects on blood glucose, body weight, 24-h urinary albumin, and renal injuries were evaluated. Microarray was used to determine the differentially expressed genes (DEGs) in the renal cortex of mice. |Log FC| <0.5 and false discovery rate (FDR) <0.25 were set as the screening criteria. Kyoto Encyclopedia of Genes and Genomes (KEGG), gene ontology (GO), protein-protein interaction (PPI) network and modules, and microRNA (miRNA)-DEGs network analysis were applied to analyze the DEGs. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the results of microarray. The present study demonstrated irbesartan could significantly improve the renal function in db/db mice through decreasing 24-h urinary albumin and alleviating the pathological injury of kidney. Irbesartan may affect the expression of numerous kidney genes involved in circadian rhythm, cell cycle, micoRNAs in cancer, and PI3K-AKT signaling pathway. In the miRNA-DEGs network, miR-1970, miR-703, miR-466f, miR-5135, and miR-132-3p were the potential targets for irbesartan treatment. The validation test confirmed that key genes regulating circadian rhythm (Arntl, Per3, and Dbp) and cell cycle (Prc1, Ccna2, and Ccnb2) were restored in db/db mice on treatment with Irbesartan. Generally, irbesartan can effectively treat DKD by regulating the circadian rhythm and cell cycle. The DEGs and pathways identified in the study will provide new insights into the potential mechanisms of irbesartan in the treatment of DKD.

Irbesartan ameliorates diabetic kidney injury in db/db mice by restoring circadian rhythm and cell cycle.

Irbesartan has been widely used in the clinical treatment of diabetic kidney disease (DKD). However, the molecular mechanism of its delay of DKD disease progression has not been fully elucidated. The aim of the present study was to investigate the mechanism of irbesartan in the treatment of DKD. C57BL/KsJ db/db mice were randomly divided into the model group and irbesartan-treated group. After treatment with irbesartan for 12 weeks, the effects on blood glucose, body weight, 24-h urinary albumin, and renal injuries were evaluated. Microarray was used to determine the differentially expressed genes (DEGs) in the renal cortex of mice. |Log FC| <0.5 and false discovery rate (FDR) <0.25 were set as the screening criteria. Kyoto Encyclopedia of Genes and Genomes (KEGG), gene ontology (GO), protein-protein interaction (PPI) network and modules, and microRNA (miRNA)-DEGs network analysis were applied to analyze the DEGs. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the results of microarray. The present study demonstrated irbesartan could significantly improve the renal function in db/db mice through decreasing 24-h urinary albumin and alleviating the pathological injury of kidney. Irbesartan may affect the expression of numerous kidney genes involved in circadian rhythm, cell cycle, micoRNAs in cancer, and PI3K-AKT signaling pathway. In the miRNA-DEGs network, miR-1970, miR-703, miR-466f, miR-5135, and miR-132-3p were the potential targets for irbesartan treatment. The validation test confirmed that key genes regulating circadian rhythm (Arntl, Per3, and Dbp) and cell cycle (Prc1, Ccna2, and Ccnb2) were restored in db/db mice on treatment with Irbesartan. Generally, irbesartan can effectively treat DKD by regulating the circadian rhythm and cell cycle. The DEGs and pathways identified in the study will provide new insights into the potential mechanisms of irbesartan in the treatment of DKD.

Potential Hepatoprotective Effects of Irbesartan, an Accessible Angiotensin II Receptor Blocker, Against Cisplatin-Induced Liver Injury in a Rat Model.

Drug-induced liver injury is a common adverse reaction that frequently occurs with chemotherapeutic agents, such as cisplatin (CIS). This study seeks to enhance our understanding of drug actions and their associated adverse effects by examining the toxicity of CIS on rat liver tissue. We aimed to investigate the potential hepatoprotective effects of irbesartan (IRB), an easily accessible angiotensin II receptor blocker, in mitigating CIS-induced hepatotoxicity. Wistar albino rats were divided into four groups. These groups included a control group [saline, per oral (p.o.)] for seven days, and 1 mL saline intraperitoneal [(i.p.) on the fourth day]; a CIS group (1 mL saline for seven days and 7.5 mg/kg CIS i.p. on the fourth day); a CIS + IRB group (IRB: 50 mg/kg p.o. for seven days and 7.5 mg/kg CIS i.p. on the fourth day), and an IRB group (50 mg/kg IRB p.o. for seven days). The effect of IRB on interleukin-1 beta (IL-1β) and caspase 3 levels was evaluated by immunohistochemical analysis, and its effects on mRNA expression levels of CCAAT/enhancer-binding protein homologous protein (CHOP) and immunoglobulin-heavy-chain-binding protein (BiP) were tested by quantitative real-time polymerase chain reaction. IRB administration mitigated CIS-induced liver toxicity by inhibiting endoplasmic reticulum (ER) stress. Specifically, this drug reduced the mRNA expression of ER stress markers, including CHOP and BiP. In addition, IRB treatment decreased oxidative stress, inflammatory responses, and apoptotic markers. These findings suggest that IRB is a promising therapeutic option for preventing CIS-induced liver injury, potentially by modulating ER stress-related pathways.

Irbesartan restored aquaporin-1 levels via inhibition of NF-kB expression in acute kidney injury model

IntroductionAcute kidney injury (AKI) is a serious pathology that progress with dysfunction of regulating blood pressure and fluid balance, concentrating urine due to decrement of aquaporin-1 (AQP) levels during the inflammation process. Irbesartan (IRN), angiotensin receptor blocker, is widely used in the treatment of hypertension, which also has anti-inflammatory, antioxidant and anti-apoptotic properties. The aim of this study is to investigate the protective effects of IRN in lipopolysaccharide (LPS)-induced kidney injury. Material and methodsTwenty-four rats divided into three groups as control, LPS and LPS+IRN group. After 6h of LPS administration, rats were sacrificed. Blood samples and half of the kidney tissues were collected for biochemical analysis and remaining tissues were taken for histopathological and immunohistochemical analysis. ResultsIn the LPS group, glomerular congestion and shrinkage, degeneration of distal tubules, mononuclear cell infiltration, cellular debris and intense proteinous accumulation in the tubules, increased expressions of Cas-3, nuclear factor kappa beta-p65 (NF-kB p65), levels of creatinin, TOS, OSI and decreased levels of TAS, AQP-1 were found significantly. IRN treatment reversed all these parameters. IRN's restorated AQP-1 levels by its anti-inflammatory, antioxidant and anti-apoptotic effects due to inhibiting NF-kB expression. ConclusionThis study suggests that IRN can be used in conditions affecting the kidneys such as AKI. Further studies needed for detailed molecular investigation of IRN at different doses and durations.

Irbesartan restored aquaporin-1 levels via inhibition of NF-kB expression in acute kidney injury model

IntroductionAcute kidney injury (AKI) is a serious pathology that progress with dysfunction of regulating blood pressure and fluid balance, concentrating urine due to decrement of aquaporin-1 (AQP) levels during the inflammation process. Irbesartan (IRN), angiotensin receptor blocker, is widely used in the treatment of hypertension, which also has anti-inflammatory, antioxidant and anti-apoptotic properties. The aim of this study is to investigate the protective effects of IRN in lipopolysaccharide (LPS)-induced kidney injury. Material and methodsTwenty-four rats divided into three groups as control, LPS and LPS+IRN group. After 6h of LPS administration, rats were sacrificed. Blood samples and half of the kidney tissues were collected for biochemical analysis and remaining tissues were taken for histopathological and immunohistochemical analysis. ResultsIn the LPS group, glomerular congestion and shrinkage, degeneration of distal tubules, mononuclear cell infiltration, cellular debris and intense proteinous accumulation in the tubules, increased expressions of Cas-3, nuclear factor kappa beta-p65 (NF-kB p65), levels of creatinin, TOS, OSI and decreased levels of TAS, AQP-1 were found significantly. IRN treatment reversed all these parameters. IRN's restorated AQP-1 levels by its anti-inflammatory, antioxidant and anti-apoptotic effects due to inhibiting NF-kB expression. ConclusionThis study suggests that IRN can be used in conditions affecting the kidneys such as AKI. Further studies needed for detailed molecular investigation of IRN at different doses and durations.

Lactobacillus induced by irbesartan on spontaneously hypertensive rat contribute to its antihypertensive effect.

Hypertension is linked to gut dysbiosis. Here, the impact of the angiotensin receptor antagonist irbesartan on the gut microbiota of spontaneously hypertensive rats (SHR) were investigated. In addition, we assessed their contribution to its antihypertensive effect. Eight-week-old Wistar-Kyoto (WKY) rats and SHR were administered irbesartan for 8 weeks. Fecal microbiota transplantation (FMT) was performed from SHR treated with irbesartan or untreated SHR to recipient untreated SHR. The preventive effect of Lactobacillus on hypertension in SHR was evaluated. Blood pressure (BP) was calculated using a tail-sleeve sphygmomanometer. To better assess the composition of the gut microbiota, the V3-V4 region of the 16S rRNA gene was amplified while short-chain fatty acids (SCFAs) in feces were tested by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). Irbesartan restored gut dysbiosis, increased the abundance of Lactobacillus , and improved anti-inflammatory ability, antioxidative ability, intestinal integrity, and intestinal inflammation in SHR. The microbiota in SHR-treated irbesartan could reduce BP and improve antioxidative ability and gut integrity in SHR. Lactobacillus johnsonii ( L. johnsonii ) and Lactobacillus reuteri ( L. reuteri ) reduced BP, restored gut dysbiosis and improved anti-inflammatory ability, antioxidative ability, intestinal integrity in SHR. Most notably, irbesartan, L. johnsonii , and L. reuteri can significantly increase SCFA content in SHR feces. The current study demonstrated that irbesartan treatment ameliorated gut dysbiosis in SHR. Irbesartan induced alterations in gut microbiota, with increased prevalence of Lactobacillus .

IRBESARTAN REDUCES LIVER DAMAGE INDUCED BY LIPOPOLYSACCHARIDE VIA INHIBITION OF TOTAL OXIDANT STATUS, INTERLEUKIN-1B AND CASPASE-3 LEVELS

Objective&#x0D; In septic conditions, hyperinflammatory response&#x0D; and hepatotoxicity are caused by oxidative stress,&#x0D; inflammation, and apoptosis. Irbesartan (IB), an&#x0D; adrenergic receptor blocker, has anti-inflammatory and&#x0D; antioxidant properties. This study aimed to investigate&#x0D; the protective effect of IB on lipopolysaccharide (LPS)-&#x0D; induced acute hepatotoxicity.&#x0D; Material and Method&#x0D; A total of eight rats were used in three groups; a control&#x0D; group; LPS group [5 mg/kg, intraperitoneally (IP)];&#x0D; and LPS + IB group [5 mg/kg LPS (IP) + 50 mg/kg IB&#x0D; (orally)]. After sacrification, tissues from the liver and&#x0D; blood were obtained for immunohistochemical and&#x0D; biochemical evaluations, such as interleukin-1 beta&#x0D; (IL-1β), caspase-3 (Cas-3) alanine aminotransferase&#x0D; (ALT), aspartate aminotransferase (AST), oxidative&#x0D; stress index (OSI), total oxidant status (TOS), and&#x0D; total antioxidant status (TAS).&#x0D; Results&#x0D; Compared with the control group, increased AST&#x0D; and ALT levels in the blood, biochemically increased&#x0D; TOS and OSI and decreased TAS levels in the&#x0D; tissue, immunohistochemically increased IL-1β, Cas-&#x0D; 3, detected. Also, in liver tissue, histopathologically&#x0D; hyperemia, hemorrhage, vacuolization, and&#x0D; significant neutrophilia infiltration were found in the&#x0D; LPS group. IB administration significantly reversed&#x0D; all these parameters. TAS levels were increased&#x0D; by IB administration, whereas TOS and OSI levels&#x0D; were decreased (p = 0.001). IB also decreased&#x0D; AST and ALT values (p = 0.001). In the IB group,&#x0D; Cas-3 and IL-1β levels were significantly decreased&#x0D; by IB administration (p = 0.001). In addition, the&#x0D; IB ameliorated histopathological findings showed&#x0D; enhanced hyperaemia, haemorrhages, vacuolisation&#x0D; and significant neutrophilic leukocyte infiltration&#x0D; (p = 0.001). IB treatment attenuated LPS-induced&#x0D; hepatotoxicity by its antioxidant, anti-inflammatory and&#x0D; antiapoptotic properties.&#x0D; Conclusion&#x0D; Attenuating liver injury and restoring liver function lowers&#x0D; morbidity and mortality rates in patients with sepsis.&#x0D; IB protects liver tissue from hepatotoxicity caused by&#x0D; LPS thanks to its antioxidant, anti-inflammatory, and&#x0D; anti-apoptotic properties. Further investigation of the&#x0D; liver’s role in sepsis may lead to the development of&#x0D; new therapeutic targets and strategies. IB may be&#x0D; an alternative therapeutic agent for the prevention of&#x0D; acute hepatotoxicity during sepsis.

DNA-dependent protein kinase catalytic subunit (DNA-PKcs) drives angiotensin II-induced vascular remodeling through regulating mitochondrial fragmentation

BackgroundDNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a novel instigator for mitochondrial dysfunction, and plays an important role in the pathogenesis of cardiovascular diseases. However, the role and mechanism of DNA-PKcs in angiotensin II (Ang II)-induced vascular remodeling remains obscure. MethodsRat aortic smooth muscle cells (SMC) and VSMC-specific DNA-PKcs knockout (DNA-PKcsΔVSMC) mice were employed to examine the role of DNA-PKcs in vascular remodeling and the underlying mechanisms. Blood pressure of mice was monitored using the tail-cuff and telemetry methods. The role of DNA-PKcs in vascular function was evaluated using vascular relaxation assessment. ResultsIn the tunica media of remodeled mouse thoracic aortas, and renal arteries from hypertensive patients, elevated DNA-PKcs expression was observed along with its cytoplasmic translocation from nucleus, suggesting a role for DNA-PKcs in vascular remodeling. We then infused wild-type (DNA-PKcsfl/fl) and DNA-PKcsΔVSMC mice with Ang II for 14 days to establish vascular remodeling, and demonstrated that DNA-PKcsΔVSMC mice displayed attenuated vascular remodeling through inhibition of dedifferentiation of VSMCs. Moreover, deletion of DNA-PKcs in VSMCs alleviated Ang II-induced vasodilation dysfunction and hypertension. Mechanistic investigations denoted that Ang II-evoked rises in cytoplasmic DNA-PKcs interacted with dynamin-related protein 1 (Drp1) at its TQ motif to phosphorylate Drp1S616, subsequently promoting mitochondrial fragmentation and dysfunction, as well as reactive oxygen species (ROS) production. Treatment of irbesartan, an Ang II type 1 receptor (AT1R) blocker, downregulated DNA-PKcs expression in VSMCs and aortic tissues following Ang II administration. ConclusionOur data revealed that cytoplasmic DNA-PKcs in VSMCs accelerated Ang II-induced vascular remodeling by interacting with Drp1 at its TQ motif and phosphorylating Drp1S616 to provoke mitochondrial fragmentation. Maneuvers targeting DNA-PKcs might be a valuable therapeutic option for the treatment of vascular remodeling and hypertension.

Lupenone improves type 2 diabetic nephropathy by regulating NF-κB pathway-mediated inflammation and TGF-β1/Smad/CTGF-associated fibrosis

BackgroundType 2 diabetic nephropathy is a common diabetic complication and the main cause of death in patients with diabetes. Research has aimed to find an ideal drug with minimal side effects for treating this disease. Banana peel has been shown to be anti-diabetic, with lupenone isolated from banana peel exhibiting antidiabetic and anti-inflammatory activities; However, the effects of lupenone on type 2 diabetic nephropathy are largely unknown. PurposeThis study aimed to investigate the ameliorative effect of lupenone on type 2 diabetic nephropathy, and its mechanism from both anti-inflammatory and anti-fibrotic perspectives. MethodsSpontaneous type 2 diabetic nephropathy db/db mouse models were given three levels of lupenone (24 or 12 or 6 mg/kg/d) via intragastric administration for six weeks, and irbesartan treatment was used for the positive control group. We explored the effects and mechanism of lupenone action using enzyme-linked immunosorbent assay, automatic biochemical analyzer, hematoxylin-eosin and Masson staining, real time-PCR, and western blotting. Concurrently, a high-sugar and high-fat diet combined with a low-dose streptozotocin-induced type 2 diabetic nephropathy rat model was used for confirmatory research. ResultsLupenone administration maintained the fasting blood glucose; reduced glycosylated hemoglobin, insulin, and 24 h proteinuria levels; and markedly regulated changes in biochemical indicators associated with kidney injury in serum and urine (including 24 h proteinuria, micro-albumin, N-acetyl-β-d-glucosaminidase, α1-micro-globulin, creatinine, urea nitrogen, uric acid, total protein, and albumin) of type 2 diabetic nephropathy mice and rats. Hematoxylin-eosin and Masson staining as well as molecular biology tests revealed that inflammation and fibrosis are the two key processes affected by lupenone treatment. Lupenone protected type 2 diabetic nephropathy kidneys by regulating the NF-κB-mediated inflammatory response and TGF-β1/Smad/CTGF pathway-associated fibrosis. ConclusionLupenone has potential as an innovative drug for preventing and treating diabetic nephropathy. Additionally, it has great value for the utilization of banana peel resources.

Immune Activation following Irbesartan Treatment in a Colorectal Cancer Patient: A Case Study

Colorectal cancers are one of the most prevalent tumour types worldwide and, despite the emergence of targeted and biologic therapies, have among the highest mortality rates. The Personalized OncoGenomics (POG) program at BC Cancer performs whole genome and transcriptome analysis (WGTA) to identify specific alterations in an individual's cancer that may be most effectively targeted. Informed using WGTA, a patient with advanced mismatch repair-deficient colorectal cancer was treated with the antihypertensive drug irbesartan and experienced a profound and durable response. We describe the subsequent relapse of this patient and potential mechanisms of response using WGTA and multiplex immunohistochemistry (m-IHC) profiling of biopsies before and after treatment from the same metastatic site of the L3 spine. We did not observe marked differences in the genomic landscape before and after treatment. Analyses revealed an increase in immune signalling and infiltrating immune cells, particularly CD8+ T cells, in the relapsed tumour. These results indicate that the observed anti-tumour response to irbesartan may have been due to an activated immune response. Determining whether there may be other cancer contexts in which irbesartan may be similarly valuable will require additional studies.

Irbesartan eases lipopolysaccharide-induced lung injury In Vitro and In Vivo.

Acute lung injury (ALI) is classified as a devastating pulmonary disorder contributing to significant incidence and fatality rate. Irbesartan (IRB) is an angiotensin II receptor blocker that has been proposed to protect against oleic acid-induced ALI. To this end, the current study is concentrated on ascertaining the role of IRB in ALI and figuring out the probable action mechanism. First, cell counting kit-8 (CCK-8) appraised the viability of human pulmonary microvascular endothelial cells (HPMVECs) exposed to ascending concentrations of IRB. HPMVEC injury model and a mouse model of ALI induced by lipopolysaccharide (LPS) were pretreated by IRB. In vitro, cell viability was estimated by CCK-8 assay, and lactate dehydrogenase (LDH) release was tested by LDH assay kit. Enzyme-linked immunosorbent assay (ELISA) and Western blotting estimated the expression levels of inflammatory factors. Fluorescein isothiocyanate-dextran was used to assess HPMVEC permeability. Western blotting examined the expression of adherent and tight junction proteins. In vivo, hematoxylin and eosin staining evaluated lung tissue damage and lung wet/dry (W/D) weight was measured. ELISA analyzed the levels of inflammatory factors in the serum and bronchoalveolar lavage fluid (BALF), and Western blotting examined the expression of inflammatory factors. The total cell, neutrophil, and macrophage numbers in BALF were determined using a cell counter. Lung capillary permeability was assayed by Evans blue albumin and total protein concentration in BALF was measured using bicinchoninic acid method. Immunofluorescence assay and Western blotting examined the expression of adherent and tight junction proteins in lung tissues. It was observed that IRB dose-dependently enhanced the viability while reduced LDH release, inflammatory response as well as permeability in LPS-challenged HPMVECs in vitro. In addition, LPS-stimulated lung tissue damage, pulmonary edema, inflammatory response as well as lung capillary permeability in vivo were all reversed following IRB treatment. Collectively, IRB treatment might elicit protective behaviors against LPS-triggered ALI.

Irbesartan ameliorates inflammation via transendothelial leukocyte migration due to VCAM-1/NOX-1 signaling in cisplatin-induced cardiotoxicity.

Cisplatin (CP) is frequently used in various types of cancers. The cardiotoxic effects of this agent limit its usage. Our study seeks to investigate the protective effects of Irbesartan (IRB) on CP-induced cardiotoxicity. The following four groups comprised thirty-two rats: control, CP, CP+IRB, and IRB. On the fourth day of the experiment, 5 mg/kg of CP was given to CP and CP+IRB groups intraperitoneally, and for seven days, water or IRB 50 mg/kg (orally) was administered. Vascular endothelial growth factor (VEGF), caspase-3 (Cas-3), vascular cell adhesion molecule-1 (VCAM-1), NADPH oxidase-1 (NOX-1), creatine kinase MB (CK-MB), and lactate dehydrogenase (LDH) were measured. The levels of VCAM-1, NOX-1, VEGF, Cas-3, and LDH were increased in the CP group. The treatment with IRB decreased VCAM-1, NOX-1, VEGF, Cas-3, and LDH levels significantly (P<0.05). Histopathological examination revealed normal heart architecture in Control and IRB groups. While marked hyperemia and myocardial cell degeneration were noticed in the CP group, significant amelioration was observed in the CP+IRB group. Aortas in the CP group showed endothelial damage and desquamation. IRB treatment markedly ameliorated histopathological findings in the CP+IRB group. Cardiac and aortic damage caused by CP was attenuated by IRB treatment owing to the anti-inflammatory and antiapoptotic effects of IRB. IRB may help reduce the severity of CP-induced cardiac injury by limiting leukocyte migration and reducing inflammation and apoptosis.

Irbesartan decreased mitochondrial stress related apoptosis in cisplatin induced acute kidney injury via regulating BCL-2/BAX signaling.

Cisplatin (CPN) is used in the treatment of various cancers. However, the especially nephrotoxic effect is limiting its use. We aimed to evaluate the renoprotective effects of Irbesartan (IBN) on CPN-induced acute kidney injury via mitochondrial stress related apoptosis. 32 rats were divided into 4 groups as control, CPN, CPN + IBN and IBN. Water or IBN 50mg/kg (orally) was administered for 7days and a single dose of CPN (5mg/kg) intraperitoneally was given CPN and CPN + IBN groups on fourth day of experiment. At the end of the experiment, serum BUN and creatinine (Cre) levels, which are the indicators of kidney function are measured. Bcl-2-associated X protein (Bax) and B-cell-lymphoma-2 (Bcl-2) mRNA levels were analyzed by using qRT-PCR from kidneys as a mitochondrial stress indicator. Also, active caspase-3(cas-3) protein and tumor necrosis factor alpha (TNF-α) expressions were examined by immunostaining of the kidney tissues. For evaluation of oxidative stress, malondialdehyde (MDA), total oxidant status (TOS) and total antioxidant status (TAS) levels of renal tissues were measured and oxidative stress index (OSI) were calculated. CPN increased serum BUN and creatinine levels. Also, MDA, TOS and OSI levels were significantly elevated and TAS levels decreased in the CPN group. Moreover, CPN elevated the levels of Bax, active cas-3 protein and TNF-α expressions and suppressed Bcl-2 levels. IBN treatment reversed all these changes. IBN significantly regressed kidney damage by its anti-inflammatory and antioxidant activity via inhibiting mitochondrial stress. IBN could be used as a renoprotective agent in CPN-induced kidney injury.

The efficacy and safety of canagliflozin in the treatment of patients with early diabetic nephropathy.

This study aimed to observe the efficacy and safety of canagliflozin in the treatment of patients with early diabetic nephropathy (DN) and investigate its effect in reducing urinary protein levels. A total of 132 patients with DN and normal renal function (estimated glomerular filtration rate >60 ml/min/1.73 m2) combined with urine albumin/creatinine ratio (UACR) no less than 30 mg/g were selected and randomly divided into a control group and an observation group, with 66 cases in each group. Irbesartan treatment was administered to the control group based on conventional treatment, while a combination of canagliflozin and irbesartan was given to the observation group based on conventional treatment. The changes in blood glucose, blood pressure, body weight, renal function, and urinary protein were observed in both groups. Compared with the control group, patients in the observation group showed a significant decrease in blood glucose, blood pressure, body weight, and urinary protein starting at week 4 of treatment and continuing until the end of the experiment at week 24 (all P<0.05). Within the observation group, blood glucose, blood pressure, body weight, and urinary protein decreased significantly with 24 weeks of treatment compared with those before the experiment (P<0.01). Patients in the observation group experienced a mild decrease in renal function at week 4, but the function began to gradually recover by week 8 and had returned to the baseline by the end of the study (P<0.05). In conclusion: canagliflozin has good efficacy and safety in the treatment of early DN. It also lowers urinary protein levels and blood glucose.

Electroacupuncture combined with irbesartan treatment improves myocardial fibrosis caused by hypertension.

Electroacupuncture combined with irbesartan treatment improves myocardial fibrosis caused by hypertension.

Protective role of irbesartan against cyclophosphamide-induced testicular damage in rats via up-regulating PPAR-γ signaling and ameliorating NF-κB/NLRP3/IL-18 inflammatory axis

BackgroundCancer and its therapies can impact fertility in various ways, and therefore a growing number of cancer survivors face fertility as a significant concern. The cytotoxic alkylating agent cyclophosphamide (CP) is commonly used as an antineoplastic agent; unfortunately, its use is significantly associated with male infertility and damage to the reproductive system. AimThe present study aimed to assess the possible beneficial effects of Irbesartan (IRB) in a rat model of CP-induced testicular toxicity. Main methodsThe effects of treatment were assessed by measuring peroxisome proliferator-activated receptor gamma (PPAR-γ) expression via qRT-PCR, the immunohistochemical (IHC) assessment of apoptotic markers, NOD-like receptor protein 3 (NLRP3), and nuclear factor-κB (NF-κB), determination of the count and viability of epididymal sperm, oxidative stress markers via biochemical analysis, serum testosterone, caspase-1, and interleukin-18 (IL-18) levels via ELISA, histopathological assessment, and fibrosis by Masson's trichrome (MT) stain. Key findingsThere was a significant increase in malondialdehyde (MDA), caspase-1, and IL-18 contents, NF-κB, NLRP3, Bcl-2-associated X protein (Bax), caspase-3, and MT staining in testicular tissue after CP administration compared to the normal control group. Whereas reduced glutathione (GSH), superoxide dismutase (SOD), PPAR-γ expression, B-cell lymphoma-2 (Bcl-2) staining, serum testosterone, and the count and viability of epididymal sperm were decreased compared to the normal control group. The IRB treatment has reversed CP-induced testicular toxicity. SignificanceIt is possible to conclude that IRB revealed a significant testicular protective effect against CP via antioxidant, anti-apoptotic, and anti-inflammatory effects.

Astragalus-Saffron-Rhubarb Mixture Delays the Progress of Diabetic Nephropathy in db/db Mice.

ObjectiveThis study aimed to investigate the protective effect of astragalus–saffron–rhubarb mixture (Bao’shen recipe, BSR) on diabetic nephropathy (DN) in db/db mice and preliminarily explore the possible underlying mechanism.MethodsA total of 125 8-week-old male db/db mice with DN were randomly divided into five groups: model group, irbesartan group and high-, medium- and low doses of BSR group, while 25 male db/m mice were used as a blank control. At 8, 12, 16, 20, and 24 weeks of feeding, the animals were sacrificed and blood as well as urine samples were collected for blood glucose, urea nitrogen, creatinine and urinary albumin excretion rate (UAER) measurement via blood glucose meter or corresponding detection kits, respectively. The renal tissues of each mouse underwent hematoxylin and eosin (H&E), Masson, periodic acid Schiff (PAS) staining. Renal homogenate was used to detect IL-6, TNF-α, TNF-1R and TNF-2R by enzyme-linked immunosorbent assay. Additionally, the data obtained was statistically analyzed via one-way analysis of variance.ResultsBSR could effectively reduce the body weight, blood glucose, UAER, blood urea nitrogen and creatinine levels, relieve the proliferation of mesangial tissue, and lower the levels of IL-6, TNF-α, TNF-1R, and TNF-2R in renal tissue of db/db mice with DN. Of note, the high-dose BSR treatment group has advantages over irbesartan treatment group in improving above-mentioned aspects.ConclusionBSR could effectively delay the progress of DN, partly related to its anti-inflammation effect.