scholarly journals Protective effect of alamandine on doxorubicin‑induced nephrotoxicity in rats

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ava Soltani Hekmat ◽  
Ameneh Chenari ◽  
Hiva Alipanah ◽  
Kazem Javanmardi
Keyword(s):  
Water Intake ◽  
Transforming Growth Factor ◽  
Immunohistochemical Analysis ◽  
Transforming Growth Factor Β ◽  
Treated Group ◽  
Protective Effects ◽  
Osmotic Pumps ◽  
Immunohistochemical Studies ◽  
Gpx Activity ◽  
Pro Inflammatory Cytokines

Abstract Background This study aimed to evaluate the protective effects of alamandine, a new member of the angiotensin family, against doxorubicin (DOX)-induced nephrotoxicity in rats. Methods Rats were intraperitoneally injected with DOX (3.750 mg/kg/week) to reach a total cumulative dose of 15 mg/kg by day 35. Alamandine (50 µg/kg/day) was administered to the rats via mini-osmotic pumps for 42 days. At the end of the experiment, rats were placed in the metabolic cages for 24 h so that their water intake and urine output could be measured. After scarification, the rats’ serum and kidney tissues were collected, and biochemical, histopathological, and immunohistochemical studies were carried out. Results DOX administration yielded increases in pro-inflammatory cytokines, including interleukin (IL)-1β and IL-6, pro-fibrotic proteins transforming growth factor-β (TGF-β), pro-inflammatory transcription factor nuclear kappa B (NF-κB), kidney malondialdehyde (MDA), creatinine clearance, blood urea nitrogen (BUN), and water intake. On the other hand, the DOX-treated group exhibited decreased renal superoxide dismutase (SOD), renal glutathione peroxidase (GPx) activity, and urinary output. Alamandine co-therapy decreased these effects, as confirmed by histopathology and immunohistochemical analysis. Conclusions The results suggest that alamandine can prevent nephrotoxicity induced by DOX‎ in rats.

scholarly journals Protective Effect of Alamandine on Doxorubicin‑Induced Nephrotoxicity in Rats

2021 ◽  
Author(s):  
Ava Soltani Hekmat ◽  
Ameneh Chenari ◽  
Hiva Alipanah ◽  
Kazem Javanmardi
Keyword(s):  
Transcription Factor ◽  
Protective Effect ◽  
Water Intake ◽  
Immunohistochemical Analysis ◽  
Treated Group ◽  
The Other ◽  
Protective Effects ◽  
Osmotic Pumps ◽  
Immunohistochemical Studies ◽  
Gpx Activity

Abstract Background: The objective of this study was to evaluate the protective effects of alamandine, a new member of the angiotensin family, against doxorubicin (DOX)-induced nephrotoxicity in rats.Methods: Rats, intraperitoneally injected with DOX (3.750 mg/kg/week) to reach total cumulative dose of 15 mg/kg on day 35. Alamandine (50µg/kg/day) was administered to the rats via mini-osmotic pumps for 42 days. At the end of experiment, rats were placed in the metabolic cages for 24 h for measurement of water intake and urine output. After scarification, Serum and kidney tissues were collected, and biochemical, histopathological and immunohistochemical studies were carried out.Results: Inflammatory cytokines (IL-1β, IL-6), pro-fibrotic mediator (TGF-β), pro-inflammatory transcription factor (NF-kB), renal MDA, creatinine clearance, BUN, and water intake were increased by DOX administration. On the other hand, renal SOD, renal GPx activity and urinary output were decreased in the DOX-treated group. Alamandine co-therapy decreased these effects, as confirmed by histopathology and immunohistochemical analysisConclusion: The results of this study suggest that alamandine has the potential in preventing the nephrotoxicity induced by DXR in rats.

scholarly journals P1196AN INIHIBITOR OF KRUPPEL-LIKE FACTOR 5 SUPPRESSES PERITONEAL FIBROSIS IN MICE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Kumiko Muta ◽  
Yuka Nakazawa ◽  
Yoko Obata ◽  
Hiro Inoue ◽  
Kenta Torigoe ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Inflammatory Responses ◽  
Retinoic Acid Receptor ◽  
Smooth Muscle Actin ◽  
Transforming Growth Factor Β ◽  
Treated Group ◽  
Peritoneal Fibrosis ◽  
Retinoic Acid Receptor Α ◽  
Klf5 Expression

Abstract Background and Aims We presented previously that Am80, a synthetic retinoic acid receptor α specific agonist, inhibited the expression of Krüppel-like transcription factor 5 (KLF5) and reduced peritoneal fibrosis in mice. Now, we examined further detail about the mechanism to inhibit peritoneal fibrosis. Method Peritoneal fibrosis was induced by intraperitoneal injection of chlorhexidine gluconate (CG) into peritoneal cavity of ICR mice. Am80 was administered orally for every day from the start of CG injection. After 3 weeks of treatment, peritoneal tissues were examined using serial sections by immunohistochemistry to identify what kind of cells expressed KLF5. We also examined the effect of Am80 to inhibit peritoneal fibrosis in vitro. Results While KLF5 was expressed in the thickened submesothelial area of CG injected mice, Am80 treatment reduced KLF5 expression and remarkably attenuated peritoneal thickening. The numbers of transforming growth factor β positive cells, α-smooth muscle actin (αSMA) or F4/80 positive cells were significantly decreased in Am80 treated group. KLF5 was expressed in αSMA, F4/80 or CD31 positive cells. Conclusion These results indicate the KLF5 might not only associate phenotypical differentiation from fibroblasts to myofibroblasts but also regulate inflammatory responses and angiogenesis in peritoneal fibrosis model. Am80 can suppress peritoneal fibrosis through inhibiting these mechanisms. In vitro experiments are ongoing.

scholarly journals Anti-Photoaging Effects of Four Insect Extracts by Downregulating Matrix Metalloproteinase Expression via Mitogen-Activated Protein Kinase-Dependent Signaling

Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 1159 ◽  
Author(s):  
A-Rang Im ◽  
Kon-Young Ji ◽  
InWha Park ◽  
Joo Young Lee ◽  
Ki Mo Kim ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Underlying Mechanism ◽  
Treated Group ◽  
Ultraviolet B ◽  
Mitogen Activated Protein Kinase ◽  
Barrier Dysfunction ◽  
Mitogen Activated Protein ◽  
Pro Inflammatory Cytokines

Insects are some of the most diverse organisms on the planet, and have potential value as food or medicine. Here, we investigated the photoprotective properties of insect extracts using hairless mice. The alleviating wrinkle formation effects of insect extracts were evaluated by histological skin analysis to determine epidermal thickness and identify collagen fiber damage. Moreover, we investigated the ability of the insect extracts to alleviate UVB-induced changes to matrix metalloproteinases (MMPs), oxidative damage, the mitogen-activated protein kinases (MAPKs) signaling pathway, and the expression of pro-inflammatory cytokines. Insect extracts reduced UVB-induced skin winkles, epidermal thickening, and collagen breakdown, and alleviated the epidermal barrier dysfunction induced by UVB, including the increased loss of transepidermal water. Moreover, the expression of skin hydration-related markers such as hyaluronic acid, transforming growth factor-beta (TGF-β), and procollagen was upregulated in the group treated with insect extracts compared to the vehicle-treated group after ultraviolet B (UVB) exposure. UVB irradiation also upregulated the expression of MMPs, the phosphorylation of MAPKs, and pro-inflammatory cytokines, which were all attenuated by the oral administration of insect extracts. These results indicate the photoaging protection effect of insect extracts and the underlying mechanism, demonstrating the potential for clinical development.

Chronic interstitial fibrosis in the rat kidney induced by long-term (6-mo) exposure to lithium

2013 ◽  
Vol 304 (3) ◽  
pp. F300-F307 ◽  
Author(s):  
Robert J. Walker ◽  
John P. Leader ◽  
Jennifer J. Bedford ◽  
Glenda Gobe ◽  
Gerard Davis ◽  
...  
Keyword(s):  
Cellular Response ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Rat Kidney ◽  
Human Kidney ◽  
Transforming Growth Factor Β ◽  
Underlying Mechanisms ◽  
Immunohistochemical Studies ◽  
Active Inflammation

There is a lack of suitable animal models that replicate the slowly progressive chronic interstitial fibrosis that is characteristic of many human chronic nephropathies. We describe a chronic long-term (6-mo) model of lithium-induced renal fibrosis, with minimal active inflammation, which mimics chronic kidney interstitial fibrosis seen in the human kidney. Rats received lithium via their chow (60 mmol lithium/kg food) daily for 6 mo. No animals died during the exposure. Nephrogenic diabetes insipidus was established by 3 wk and persisted for the 6 mo. Following metabolic studies, the animals were killed at 1, 3, and 6 mo and the kidneys were processed for histological and immunohistochemical studies. Progressive interstitial fibrosis, characterized by increasing numbers of myofibroblasts, enhanced transforming growth factor-β1 expression and interstitial collagen deposition, and a minimal inflammatory cellular response was evident. Elucidation of the underlying mechanisms of injury in this model will provide a greater understanding of chronic interstitial fibrosis and allow the development of intervention strategies to prevent injury.

Antagonistic Effects of Insulin and TGF-β3 during Chondrogenic Differentiation of Human BMSCs under a Minimal Amount of Factors

2016 ◽  
Vol 201 (2) ◽  
pp. 88-96 ◽  
Author(s):  
Emilio Satoshi Hara ◽  
Mitsuaki Ono ◽  
Yuya Yoshioka ◽  
Junji Ueda ◽  
Yuri Hazehara ◽  
...  
Keyword(s):  
Chondrogenic Differentiation ◽  
Transforming Growth Factor ◽  
Direct Interaction ◽  
Transforming Growth Factor Β ◽  
Treated Group ◽  
Minimal Amount ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Antagonistic Effects

Growth factors are crucial regulators of cell differentiation towards tissue and organ development. Insulin and transforming growth factor-β (TGF-β) have been used as the major factors for chondrogenesis in vitro, by activating the AKT and Smad signaling pathways. Previous reports demonstrated that AKT and Smad3 have a direct interaction that results in the inhibition of TGF-β-mediated cellular responses. However, the result of this interaction between AKT and Smad3 during the chondrogenesis of human bone marrow-derived stem/progenitor cells (hBMSCs) is unknown. In this study, we performed functional analyses by inducing hBMSCs into chondrogenesis with insulin, TGF-β3 or in combination, and found that TGF-β3, when applied concomitantly with insulin, significantly decreases an insulin-induced increase in mRNA levels of the master regulator of chondrogenesis, SOX9, as well as the regulators of the 2 major chondrocyte markers, ACAN and COL2A1. Similarly, the insulin/TGF-β3-treated group presented a significant decrease in the deposition of cartilage matrix as detected by safranin O staining of histological sections of hBMSC micromass cultures when compared to the group stimulated with insulin alone. Intracellular analysis revealed that insulin-induced activation of AKT suppressed Smad3 activation in a dose-dependent manner. Accordingly, insulin/TGF-β3 significantly decreased the TGF-β3-induced increase in mRNA levels of the direct downstream factor of TGF-β/Smad3, CCN2/CGTF, compared to the group stimulated with TGF-β3 alone. On the other hand, insulin/TGF-β3 stimulation did not suppress insulin-induced expression of the downstream targets TSC2 and DDIT4/REDD1. In summary, insulin and TGF-β3 have antagonistic effects when applied concomitantly, with a minimal number of factors. The application of an insulin/TGF-β3 combination without further supplementation should be used with caution in the chondrogenic differentiation of hBMSCs.

scholarly journals Recent Insights into the Biological Functions of Sestrins in Health and Disease

2017 ◽  
Vol 43 (5) ◽  
pp. 1731-1741 ◽  
Author(s):  
Menglong Wang ◽  
Yao Xu ◽  
Jianfang Liu ◽  
Jing Ye ◽  
Wenhui Yuan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transforming Growth Factor ◽  
Kidney Diseases ◽  
Heart Diseases ◽  
Neurological Diseases ◽  
Mammalian Target Of Rapamycin ◽  
Hypoxia Inducible Factor ◽  
Transforming Growth Factor Β ◽  
Protective Effects ◽  
Immunological Diseases

Sestrins (Sesns) have been identified as a family of highly conserved stress-inducible proteins that are strongly up-regulated by various stresses, including DNA damage, oxidative stress, and hypoxia. The Sesns play protective roles in most physiological and pathological conditions mainly through the regulation of oxidative stress, inflammation, autophagy, endoplasmic reticulum stress, and metabolic homeostasis. In this review, we discussed the possible regulators of Sesns expression, such as p53, forkhead box O, nuclear factor erythroid 2 like 2 (Nrf2), NH (2)-terminal kinase (JNK)/c-Jun pathway and hypoxia-inducible factor-1α (Hif-1α), and the downstream pathways regulated by the Sesns including AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling, mitogen-activated protein kinases (MAPKs) signaling, Nrf2 signaling, NADPH oxidase signaling and transforming growth factor β (TGF-β) signaling in heart diseases, lung diseases, gastrointestinal tract diseases, liver and metabolism diseases, neurological diseases, kidney diseases and immunological diseases. This review aims to provide a comprehensive understanding the protective effects of Sesns.

scholarly journals Melatonin Alleviates Contrast-Induced Acute Kidney Injury by Activation of Sirt3

2021 ◽  
Vol 2021 ◽  
pp. 1-21
Author(s):  
Chunmei Zhang ◽  
Mengying Suo ◽  
Lingxin Liu ◽  
Yan Qi ◽  
Chen Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Transforming Growth Factor ◽  
Kidney Injury ◽  
Transforming Growth Factor Β ◽  
Activity Levels ◽  
Protective Effects ◽  
Melatonin Treatment

Oxidative stress and apoptosis play a vital role in the pathogenesis of contrast-induced acute kidney injury (CI-AKI). The purpose of our study was to investigate the protective effects and mechanisms of melatonin against CI-AKI in a CI-AKI mouse model and NRK-52E cells. We established the CI-AKI model in mice, and the animals were pretreated with melatonin (20 mg/kg). Our results demonstrated that melatonin treatment exerted a renoprotective effect by decreasing the level of serum creatinine (SCr) and blood urea nitrogen (BUN), lessening the histological changes of renal tubular injuries, and reducing the expression of neutrophil gelatinase-associated lipid (NGAL), a marker of kidney injury. We also found that pretreatment with melatonin remarkably increased the expression of Sirt3 and decreased the ac-SOD2 K68 level. Consequently, melatonin treatment significantly decreased the oxidative stress by reducing the Nox4, ROS, and malondialdehyde (MDA) content and by increasing the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity levels. The antiapoptotic effect of melatonin on CI-AKI was revealed by decreasing the ratio of Bax/Bcl2 and the cleaved caspase3 level and by reducing the number of apoptosis-positive tubular cells. In addition, melatonin treatment remarkably reduced the inflammatory cytokines of interleukin-1β (IL-1β), tumor necrosis factor α (TNFα), and transforming growth factor β (TGFβ) in vivo and in vitro. Sirt3 deletion and specific Sirt3 siRNA abolished the above renoprotective effects of melatonin in mice with iohexol-induced acute kidney injury and in NRK-52E cells. Thus, our results demonstrated that melatonin exhibited the renoprotective effects of antioxidative stress, antiapoptosis, and anti-inflammation by the activation of Sirt3 in the CI-AKI model in vivo and in vitro. Melatonin may be a potential drug to ameliorate CI-AKI in clinical practice.

scholarly journals Transforming Growth Factor β and Immunosuppression in Experimental Visceral Leishmaniasis

1998 ◽  
Vol 66 (3) ◽  
pp. 1233-1236 ◽  
Author(s):  
Virmondes Rodrigues ◽  
João Santana da Silva ◽  
Antonio Campos-Neto
Keyword(s):  
T Cells ◽  
Growth Factor ◽  
Visceral Leishmaniasis ◽  
Leishmania Donovani ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Spleen Cells ◽  
Immunohistochemical Studies

ABSTRACT Hamsters infected with Leishmania donovani develop a disease similar to human kala-azar. They present hypergammaglobulinemia, and their T cells do not respond to parasite antigens. This unresponsiveness has been primarily ascribed to defects in antigen-presenting cells (APCs), because these cells are unable to stimulate proliferation of parasite-specific T cells from immunized animals. In this study, we show that APCs (adherent spleen cells) fromL. donovani-infected hamsters produce high levels of the inhibitory cytokine transforming growth factor β (TGF-β). Immunohistochemical studies with an anti-TGF-β monoclonal antibody (MAb) showed that this cytokine is abundantly produced in vivo by the spleen cells of infected animals. In addition, high levels of TGF-β are produced in vitro by infected hamster cells, either spontaneously or after stimulation with parasite antigen or lipopolysaccharide. Furthermore, in vivo-infected adherent cells obtained from spleens ofL. donovani-infected hamsters caused profound inhibition of the in vitro antigen-induced proliferative response of lymph node cells from hamsters immunized with leishmanial antigens. Moreover, this inhibition was totally abrogated by the anti-TGF-β MAb. These results suggest that the immunosuppression observed in visceral leishmaniasis is, at least in part, due to the abundant production of TGF-β during the course of the infection.

scholarly journals Protective Effects of Flavone from Tamarix aphylla against CCl4-Induced Liver Injury in Mice Mediated by Suppression of Oxidative Stress, Apoptosis and Angiogenesis

2019 ◽  
Vol 20 (20) ◽  
pp. 5215 ◽  
Author(s):  
Bishoy El-Aarag ◽  
Asmaa Khairy ◽  
Shaden A. M. Khalifa ◽  
Hesham R. El-Seedi
Keyword(s):  
Liver Injury ◽  
Transforming Growth Factor ◽  
B Cell Lymphoma ◽  
Immunohistochemical Analysis ◽  
Transforming Growth Factor Β1 ◽  
Protective Effects ◽  
Beneficial Effects ◽  
Protein Levels ◽  
Pre Treatment ◽  
Mice Liver

The current study aimed to investigate, for the first time, the beneficial effects of 3,5-dihydroxy-4′,7-dimethoxyflavone isolated from Tamarix aphylla L. against liver injury in mice. Liver injury was induced by intraperitoneal (i.p.) injection of carbon tetrachloride (CCl4) at a dose of 0.4 mL/kg mixed in olive oil at ratio (1:4) twice a week for 6 consecutive weeks. The administration of CCl4 caused significant histopathological changes in liver tissues while the pre-treatment with the flavone at dose of 10 and 25 mg/kg ameliorated the observed liver damages. Also, it markedly reduced hepatic malondialdehyde (MDA) level as well as increased the activities of liver superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (Gpx) compared with their recorded levels in CCl4 model group. Moreover, the immunohistochemical analysis demonstrated the enhancement in the protein level of B-cell lymphoma-2 (Bcl-2) while the protein levels of cysteine-aspartic acid protease-3 (caspase-3), Bcl-2-associated x protein (Bax), transforming growth factor-β1 (TGF-β1) and CD31 were suppressed following the flavone treatement. These results suggest that the flavone can inhibit liver injury induced in mice owning to its impact on the oxidation, apoptotic and angiogenesis mechanisms. Further pharmacological investigations are essential to determine the effectiveness of the flavone in human.

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