The nutraceutical antihypertensive action of C-phycocyanin in chronic kidney disease is related to the prevention of endothelial dysfunction

C-phycocyanin (CPC) is an antihypertensive that is not still wholly pharmacologically described. The aim of this study was to evaluate whether CPC counteracts endothelial dysfunction as an antihypertensive mechanism in rats with 5/6 nephrectomy (NFx) as a chronic kidney disease (CKD) model. Twenty-four male Wistar rats were divided into four groups: sham control, sham-treated with CPC (100 mg/Kg/d), NFx, and NFx treated with CPC. Blood pressure was measured each week, and renal function evaluated at the end of the treatment. Afterward, animals were euthanized, and their thoracic aortas were analyzed for endothelium functional test, oxidative stress, and NO production. 5/6 Nephrectomy caused hypertension increasing lipid peroxidation and ROS production, overexpression of inducible nitric oxide synthase (iNOS), reduction in the first-line antioxidant enzymes activities, and reduced-glutathione (GSH) with a down-expression of eNOS. The vasomotor response reduced endothelium-dependent vasodilation in aorta segments exposed to acetylcholine and sodium nitroprusside. However, the treatment with CPC prevented hypertension by reducing oxidative stress, NO system disturbance, and endothelial dysfunction. The CPC treatment did not prevent CKD-caused disturbance in the antioxidant enzymes activities. Therefore, CPC exhibited an antihypertensive activity while avoiding endothelial dysfunction

Antioxidant and Hypoglycaemic Effects of Ardisia Compressa (HBEK, Myrsinaceae) Extract in Type 2 Diabetic Rats

Purpose: To evaluate the possible hypoglycaemic, hypolipidemic, and antioxidant activities of Ardisia compressa (AC) on a rat model of type 2 diabetes.Methods: Diabetes was induced in female Wistar rats by intraperitoneal (i.p.) administration of streptozotocin (65 mg/kg) and nicotinamide (120 mg/kg). The diabetic animals were orally administered water with or without metformin 150 mg/kg (D+Met) or 100, 200, or 400 mg/kg AC (D+100, 200 or 400), daily for 21 days. Normoglycaemic animals were given water with or without 400 mg/kg AC. Glycaemia, urinary protein excretion, lipid profiles, and antioxidant activity were determined.Results: AC decreased hyperglycaemia in diabetic animals (150.67 ± 13.41 mg/dL, AC vs. 346.33 ± 51.21 mg/dL, Diabetes), but not hyperlipidemia. An antioxidant effect was also observed in the 400- mg/kg AC extract group, which exhibited significantly decreased lipid peroxidation (2.597 ± 0.284, AC vs. 3.623 ± 0.280 μM malondialdehyde [MDA]/g, Diabetes) and reactive oxygen species (ROS) production (1.533 ± 0.207, AC vs. 5.281 ± 0.457 μg DCF/mg, Diabetes) in liver. In addition, lipid peroxidation, ROS, and oxidised proteins levels were decreased in the kidneys and pancreas of AC treated diabetic animals.Conclusion: AC leaves exert hypoglycaemic and antioxidant effects in type 2 diabetic rats, and has the potential to delay or prevent the onset of diabetes-induced complications.Keywords: Type 2 diabetes, Ardisia compressa, Hypoglycaemia, Lipidaemia, Reactive oxygen species, Oxidative stres

C-phycoerythrin from Phormidium persicinum prevents acute kidney injury by attenuating oxidative and endoplasmic reticulum stress.

C-phycoerythrin (C-PE) is a phycobiliprotein that prevents oxidative stress and cell damage. The aim of this study was to evaluate whether C-PE also counteracts endoplasmic reticulum (ER) stress as a mechanism contributing to its nephroprotective activity. After C-PE was purified from Phormidium persicinum by using size exclusion chromatography, it was characterized by spectrometry and fluorometry. A mouse model of HgCl2-induced acute kidney injury (AKI) was used to assess the effect of C-PE treatment (at 25, 50, or 100 mg/kg of body weight) on oxidative stress, the redox environment, and renal damage. ER stress was examined with the same model and C-PE treatment at 100 mg/kg. C-PE diminished oxidative stress and cell damage in a dose-dependent manner by impeding the decrease in expression of nephrin and podocin normally caused by mercury intoxication. It reduced ER stress by preventing the activation of the inositol-requiring enzyme-1α (IRE1α) pathway and avoiding caspase-mediated cell death, while leaving the expression of protein kinase RNA-like ER kinase (PERK) and activating transcription factor 6α (ATF6α) pathways unmodified. Hence, C-PE exhibited a nephroprotective effect on HgCl2-induced AKI by reducing oxidative stress and ER stress

Endoplasmic reticulum stress participates in the pathophysiology of mercury-caused acute kidney injury

PubMedID: 31736398Acute exposure to mercury chloride (HgCl2) causes acute kidney injury (AKI). Some metals interfere with protein folding, leading to endoplasmic reticulum stress (ERS), and the activation of cell death mechanisms, but in the case of mercury, there is no knowledge about whether the ERS mediates tubular damage. This study aimed to determinate if HgCl2 causes an AKI course with temporary activation of ERS and if this mechanism is involved in kidney cell death. Male mice were intoxicated with 5 mg/kg HgCl2 and sacrificed after 24, 48, 72, and 96 h of mercury administration. The kidneys of euthanized mice were used to assess the renal function, oxidative stress, redox environment, antioxidant enzymatic system, cell death, and reticulum stress markers (PERK, ATF-6, and IRE1? pathways). The results indicate temporary-dependent renal dysfunction, oxidative stress, and an increase of glutathione-dependent enzymes involved in the bioaccumulation process of mercury, as well as the enhancement of caspase 3 activity along with IRE1a, GADD-153, and caspase 12 expressions. Mercury activates the PERK/eIF2? branch during the first 48 h. Meanwhile, the activation of PERK/ATF-4 branch allowed for ATF-4, ATF-6, and IRE1? pathways to enhance GADD-153. It led to the activation of caspases 12 and 3, which mediated the deaths of the tubular and glomerular cells. This study revealed temporary-dependent ERS present during AKI caused by HgCl2, as well as how it plays a pivotal role in kidney cell damage. © 2019, © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.Secretaría de Investigación y Posgrado, Instituto Politécnico Nacional Consejo Nacional de Ciencia y TecnologíaEdgar Cano-Europa thanks COTEBAL-IPN for the support given this year for the realization of this project. The authors thank INSTITUTO POLITÉCNICO NACIONAL, SECRETARÍA DE INVESTIGACIÓN Y POSGRADO-IPN, and CONACyT for financial support. The researchers are fellows of EDI, COFAA, and SNI

C-phycoerythrin from phormidium persicinum prevents acute kidney injury by attenuating oxidative and endoplasmic reticulum stress

C-phycoerythrin (C-PE) is a phycobiliprotein that prevents oxidative stress and cell damage. The aim of this study was to evaluate whether C-PE also counteracts endoplasmic reticulum (ER) stress as a mechanism contributing to its nephroprotective activity. After C-PE was purified from Phormidium persicinum by using size exclusion chromatography, it was characterized by spectrometry and fluorometry. A mouse model of HgCl2-induced acute kidney injury (AKI) was used to assess the effect of C-PE treatment (at 25, 50, or 100 mg/kg of body weight) on oxidative stress, the redox environment, and renal damage. ER stress was examined with the same model and C-PE treatment at 100 mg/kg. C-PE diminished oxidative stress and cell damage in a dose-dependent manner by impeding the decrease in expression of nephrin and podocin normally caused by mercury intoxication. It reduced ER stress by preventing the activation of the inositol-requiring enzyme1α (IRE1α) pathway and avoiding caspase-mediated cell death, while leaving the expression of protein kinase RNA-like ER kinase (PERK) and activating transcription factor 6α (ATF6α) pathways unmodified. Hence, C-PE exhibited a nephroprotective effect on HgCl2-induced AKI by reducing oxidative stress and ER stress