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Effects of Irbesartan Pretreatment on Pancreatic ?-Cell Apoptosis in STZ-Induced Acute Prediabetic Mice.

ABSTRACT: The current study was performed to investigate the effects and potential effects of irbesartan pretreatment on pancreatic ?-cell apoptosis in a streptozotocin- (STZ-) induced acute mouse model of prediabetes. Twenty-four male BALB/C mice (18-22?g) were randomly divided into three groups: normal control group (NC, n = 6), STZ group (STZ, n = 8), and irbesartan?+?STZ group (IRB?+?STZ, n = 10). In the IRB?+?STZ group, mice were administered irbesartan (300?mg/kg per day) by gavage for one week. The STZ group and IRB?+?STZ group received STZ (80?mg/kg by intraperitoneal (IP) injection once). The NC group received normal saline (80?mg/kg by IP injection once). Fasting blood glucose prior to STZ injection and presacrifice was analysed using samples withdrawn from the caudal vein to confirm the induction of prediabetes. Haematoxylin and eosin staining, immunohistochemical detection of insulin, and apoptosis analysis were performed. Reverse transcription-quantitative polymerase chain reaction was used to detect angiotensin II type 1 receptor (AT1R), caspase-3, and p38 mitogen-activated protein kinase (MAPK) mRNA expression. Blood glucose was significantly higher in the STZ group (9.01?±?1.1089 vs 4.78?±?0.7026) and IRB?+?STZ group (7.86?±?1.1811 vs 4.78?±?0.7026) compared with the NC group (P < 0.05). In comparison to the STZ group, the islet cell damage was marginally improved in the IRB?+?STZ group, and the IRB?+?STZ group had a significantly lower apoptotic rate than the STZ group (22.42?±?8.3675 vs 50.86?±?5.3395, P < 0.001). AT1R expression in the IRB?+?STZ group was lower than that in the STZ group (1.56?±?1.2207 vs 3.92?±?2.4392, P < 0.05). The mRNA expression of caspase-3 in pancreatic tissue was significantly lower in the IRB?+?STZ group than in the STZ group (0.90?±?0.7272 vs 1.88?±?1.0572, P < 0.05). Similarly, the IRB?+?STZ group also had lower p38MAPK levels than the STZ group (1.16?±?1.0642 vs 2.55?±?1.7925, P > 0.05). In conclusion, irbesartan pretreatment improved glucose levels and insulin secretion and decreased islet ?-cell apoptosis to protect islet ? cells in an STZ-induced acute prediabetic mouse model.

SUBMITTER: Chen C

PROVIDER: S-EPMC6304884 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Effects of Irbesartan Pretreatment on Pancreatic β-Cell Apoptosis in STZ-Induced Acute Prediabetic Mice.

Chen Cuihong C Li Li L Qin Haijing H Huang Zhenxing Z Xian Jing J Cai Jinwei J Qin Yingfen Y Zhang Jie J Liang Xinghuan X

Oxidative medicine and cellular longevity 20181202

The current study was performed to investigate the effects and potential effects of irbesartan pretreatment on pancreatic β-cell apoptosis in a streptozotocin- (STZ-) induced acute mouse model of prediabetes. Twenty-four male BALB/C mice (18-22 g) were randomly divided into three groups: normal control group (NC, n = 6), STZ group (STZ, n = 8), and irbesartan + STZ group (IRB + STZ, n = 10). In the IRB + STZ group, mice were administered irbesartan (300 mg/kg per day) ...[more]

PMID: 30622676

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Project description:Persistent hyperglycemia is known to cause enhanced generation of reactive oxygen species in diabetes. Several inflammatory cytokines are induced by oxidative stress, and their release also leads to increased oxidative stress; this makes oxidative stress one of the important factors in the development of chronic inflammation and other immune responses. These have been implicated in the development of diabetic complications such as nephropathy and cardiomyopathy. Anchomanes difformis has been shown to possess antioxidant and anti-inflammatory potentials. The present study investigated the immunomodulatory potential and the antiapoptotic ability of Anchomanes difformis to ameliorate heart toxicity and injury in type II diabetes. Two weeks of fructose (10%) administration followed by single intraperitoneal injection of streptozotocin (40 mg/kg) were used to induce type II diabetes in male Wistar rats. Leaf extract (aqueous) of Anchomanes difformis (200 and 400 mg/kg) was administered orally for six weeks. Blood glucose concentrations and body weights before and after interventions were determined. Interleukin (IL)-1?, IL-6, IL-10, IL-18, monocyte chemoattractant protein 1 (MCP-1), and tumor necrosis factor alpha (TNF?) were measured in the heart homogenates. Catalase (CAT), superoxide dismutase (SOD), total protein, oxygen radical absorbance capacity (ORAC), ferric reducing antioxidant power (FRAP), thiobarbituric acid reactive substances (TBARS), and heart-type fatty acid-binding protein (H-FABP) levels were determined. Expressions of transcription factors (Nrf 2 and NFkB/p65) and apoptotic markers were also investigated in the heart. Anchomanes difformis administration reduced pro-inflammatory cytokines, increased anti-inflammatory markers, and enhanced antioxidant defense in the heart of diabetic treated animals. Anchomanes difformis is a new, promising therapeutic agent that can be explored for the treatment of pathological conditions associated with immune responses and will be a useful tool in the management of associated diabetic complications.

Project description:BackgroundThe complement system plays a critical role as the pathogenic factor in the models of acute lung injury due to various causes. Cobra venom factor (CVF) is a commonly used complement research tool. The CVF can cause acute inflammation in the lung by producing complement activation components. Atorvastatin (ATR) is a 3-hydroxy-3-methylglutaryl coenzyme A inhibitor approved for control of plasma cholesterol levels. This inhibitor can reduce the acute pulmonary inflammatory response. However, the ability of ATR in treating acute lung inflammation caused by complement activation is still unknown. Therefore, we investigated the effect of ATR on lung inflammation in mice induced by activation of the complement alternative pathway in this study.MethodsATR (10 mg/kg/day via oral gavage) was administered for 7 days before tail vein injection of CVF (25 μg/kg). On the seventh day, all mice were sacrificed 1 h after injection. The lung lobe, bronchoalveolar lavage fluid (BALF), and blood samples were collected. The myeloperoxidase (MPO) activity of the lung homogenate, the leukocyte cell count, and the protein content of BALF were measured. The levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), P-selectin, and Intercellular cell adhesion molecule-1 (ICAM-1) in BALF and serum were determined by enzyme-linked immunosorbent assay. The pathological change of the lung tissue was observed by hematoxylin and eosin staining. The deposition of C5b-9 in the lung tissue was detected by immunohistochemistry. The phosphorylation of NF-κB p65 in the lung tissues was examined by immunohistochemistry and western blotting.ResultsThe lung inflammation levels were determined by measuring the leukocyte cell numbers and protein content of BALF, the lung MPO activity, and expression and staining of the inflammatory mediators (IL-6 and TNF-α), and adhesion molecules (P-selectin and ICAM-1) for lung lesion. A significant reduction in the lung inflammation levels was observed after 7 days in ATR pre-treated mice with a CVF-induced lung disease. Deposition of C5b-9 was significantly alleviated by ATR pretreatment. Early intervention with ATR significantly reduced the development of acute lung inflammation on the basis of phosphorylation of NF-κB p65 in the lung.ConclusionThese findings suggest the identification of ATR treatment for the lung inflammation induced by activating the complement system on the basis of its anti-inflammatory response. Together with the model replicating the complement activating characteristics of acute lung injury, the results may be translatable to the overactivated complement relevant diseases.

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Dataset Information

Effects of Irbesartan Pretreatment on Pancreatic ?-Cell Apoptosis in STZ-Induced Acute Prediabetic Mice.

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Effects of Irbesartan Pretreatment on Pancreatic <i>β</i>-Cell Apoptosis in STZ-Induced Acute Prediabetic Mice.

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