ABSTRACT
The central exacerbating factor in the pathophysiology of ischemic-reperfusion acute kidney injury (AKI) is oxidative stress. Lipid peroxidation and DNA damage in ischemia are accompanied by the formation of 3-nitrotyrosine, a biomarker for oxidative damage. DNA double-strand breaks (DSBs) may also be a result of postischemic AKI. γH2AX(S139) histone has been identified as a potentially useful biomarker of DNA DSBs. On the other hand, hypoxia-inducible factor (HIF) is the "master switch" for hypoxic adaptation in cells and tissues. The aim of this research was to evaluate the influence of hyperbaric oxygen (HBO) preconditioning on antioxidant capacity estimated by FRAP (ferric reducing antioxidant power) and ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) assay, as well as on oxidative stress parameter 3-nitrotyrosine, and to assess its effects on γH2AX(S139), HIF-1α, and nuclear factor-κB (NF-κB) expression, in an experimental model of postischemic AKI induced in spontaneously hypertensive rats. The animals were divided randomly into three experimental groups: sham-operated rats (SHAM, n = 6), rats with induced postischemic AKI (AKI, n = 6), and group exposed to HBO preconditioning before AKI induction (AKI + HBO, n = 6). A significant improvement in the estimated glomerular filtration rate, eGFR, in AKI + HBO group (p < 0.05 vs. AKI group) was accompanied with a significant increase in plasma antioxidant capacity estimated by FRAP (p < 0.05 vs. SHAM group) and a reduced immunohistochemical expression of 3-nitrotyrosine and γH2AX(S139). Also, HBO pretreatment significantly increased HIF-1α expression (p < 0.001 vs. AKI group), estimated by Western blot and immunohistochemical analysis in kidney tissue, and decreased immunohistochemical NF-κB renal expression (p < 0.01). Taking all of these results together, we may conclude that HBO preconditioning has beneficial effects on acute kidney injury induced in spontaneously hypertensive rats.
Subject(s)
Acute Kidney Injury , Hyperbaric Oxygenation , Reperfusion Injury , Animals , Rats , Acute Kidney Injury/etiology , Acute Kidney Injury/therapy , Antioxidants , Biomarkers , DNA Damage , Kidney , NF-kappa B , Oxidative Stress , Oxygen , Rats, Inbred SHRABSTRACT
Lifestyle modifications such as increase in high-fat food consumption importantly increases the risks for cardiovascular disease. The principal objective of this study is to analyze effects of different high fat diet (HFD) sources on haemodynamic parameters, lipid and oxidative profile, myeloperoxidase activity, and markers of inflammation (IL-6/pentraxin-3). HFD containing 20% of fat, provided by lard (saturated) or soybean oil (unsaturated), as well as control diet were administering to three groups (L, SO and C). Food efficiency ratio and plasma lipids were significantly elevated in both HFD groups. However, only SO group showed an increase in systolic arterial pressure, oxidative stress index, myeloperoxidase activity, liver lipids as well as markers of inflammation: IL-6 and pentraxin-3 (PTX3). In summary, these results indicate inflammogenic potential of excessive soybean oil consumption in triggering liver damage.
Subject(s)
Fatty Acids, Unsaturated/administration & dosage , Inflammation/chemically induced , Inflammation/metabolism , Oxidative Stress/physiology , Animals , Biomarkers/metabolism , C-Reactive Protein/metabolism , Diet, High-Fat/adverse effects , Dietary Fats/adverse effects , Interleukin-6/metabolism , Liver/metabolism , Male , Peroxidase/metabolism , Rats , Rats, Wistar , Serum Amyloid P-Component/metabolism , Soybean Oil/adverse effectsABSTRACT
Renal ischemia and reperfusion (I/R) injury is the most common cause of acute kidney injury (AKI). Pathogenesis of postischemic AKI involves hemodynamic changes, oxidative stress, inflammation process, calcium ion overloading, apoptosis and necrosis. Up to date, therapeutic approaches to treat AKI are extremely limited. Thus, the aim of this study was to evaluate the effects of hyperbaric oxygen (HBO) preconditioning on citoprotective enzyme, heme oxygenase-1 (HO-1), pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins expression, in postischemic AKI induced in normotensive Wistar and spontaneously hypertensive rats (SHR). The animals were randomly divided into six experimental groups: SHAM-operated Wistar rats (W-SHAM), Wistar rats with induced postischemic AKI (W-AKI) and Wistar group with HBO preconditioning before AKI induction (W-AKI + HBO). On the other hand, SHR rats were also divided into same three groups: SHR-SHAM, SHR-AKI and SHR-AKI + HBO. We demonstrated that HBO preconditioning upregulated HO-1 and anti-apoptotic Bcl-2 protein expression, in both Wistar and SH rats. In addition, HBO preconditioning improved glomerular filtration rate, supporting by significant increase in creatinine, urea and phosphate clearances in both rat strains. Considering our results, we can also say that even in hypertensive conditions, we can expect protective effects of HBO preconditioning in experimental model of AKI.
Subject(s)
Acute Kidney Injury/prevention & control , Heme Oxygenase (Decyclizing)/metabolism , Hyperbaric Oxygenation/methods , Hypertension/complications , Proto-Oncogene Proteins c-bcl-2/metabolism , Reperfusion Injury/prevention & control , Acute Kidney Injury/etiology , Acute Kidney Injury/pathology , Acute Kidney Injury/urine , Animals , Creatinine/metabolism , Creatinine/urine , Disease Models, Animal , Humans , Hypertension/physiopathology , Hypertension/therapy , Kidney/blood supply , Kidney/pathology , Kidney/physiopathology , Male , Oxygen/administration & dosage , Phosphates/metabolism , Phosphates/urine , Rats , Rats, Inbred SHR , Rats, Wistar , Renal Elimination/physiology , Reperfusion Injury/etiology , Reperfusion Injury/pathology , Reperfusion Injury/urine , Up-Regulation , Urea/metabolism , Urea/urineABSTRACT
Olive (Olea europaea L.) leaf extract (OLE) possesses powerful antioxidant, antihyperlipidemic, and anti-inflammatory properties. The aim was to investigated the effects of OLE on the hyperlipidemia, antioxidant defense, heme oxygenase/biliverdin reductase (HO/BVR) pathway, inflammation, and fibrosis in spontaneously hypertensive rats with focal segmental glomerulosclerosis (FSGS, a progressive form of chronic kidney disease) induced by adriamycin (2 mg/kg, i.v., twice in a 21-day period). Daily treatment of OLE (80 mg/kg, p.o.) for 6 weeks suppressed protein oxidation and lipid peroxidation (p < .01 and p < .001, respectively), significantly increased antioxidant enzymes activities and normalized antioxidant capacity, leading to the improvement of antioxidant defense independently of the HO/BVR pathway. Furthermore, the values of triglycerides (p < .01), total, and low-density lipoprotein cholesterol (p < .05, both) were improved by OLE. OLE strongly prevented glomerulosclerosis, interstitial inflammation, and fibrosis (renal injury score, FSGS: 8 ± 0.45 vs. FSGS+OLE: 4.20 ± 1.07; p < .01), as evidenced by normalized fibronectin content (p < .001), suppressed interstitial inflammatory cells infiltration and collagen deposition, without changing cytokines expressions. OLE decreased blood pressure with a tendency to reduce urine albumin loss. These data suggest that OLE may be effective in slowing down the progression of FSGS.
Subject(s)
Antioxidants/therapeutic use , Doxorubicin/adverse effects , Fibrosis/drug therapy , Glomerulosclerosis, Focal Segmental/chemically induced , Glomerulosclerosis, Focal Segmental/drug therapy , Hyperlipidemias/drug therapy , Olea/chemistry , Oxidative Stress/drug effects , Animals , Antioxidants/pharmacology , Female , RatsABSTRACT
Background: Acute kidney injury (AKI) as a consequence of ischemia is a common clinical event that can lead to unacceptably high morbidity and mortality. Hyperbaric oxygen (HBO2) preconditioning has been shown to prevent ischemia-reperfusion injury (IRI) in different tissues. Objectives: The aim of our study was to compare the effects of HBO2 preconditioning on renal hemodynamics, kidney function and oxidative stress in normotensive and spontaneously hypertensive rats that suffered kidney IRI. Methods: An experiment was performed on Wistar (normotensive) and spontaneously hypertensive rats (SHR). The animals were divided into the following experimental groups: sham-operated rats and rats with or without HBO2 preconditioning 24 hours before post-ischemic AKI induction. Treated rats were placed into experimental HBO2 chambers and exposed to pure oxygen twice a day for two consecutive days (2.026 bar of oxygen) for 60 minutes. AKI was performed the next morning. The right kidney was removed and the renal ischemia was performed by clamping the left renal artery for 45 minutes. Results: In this study, HBO2 preconditioning significantly improved disturbed renal hemodynamics, major markers of kidney function in plasma (creatinine, urea and phosphate) as well as antioxidant enzymes (superoxide dismutase and catalase) activities in erythrocytes after AKI induction. Also, HBO2 preconditioning decreased lipid peroxidation in plasma after ischemic AKI. Positive effects were observed in both strains of rats. Conclusions: Our results suggest that HBO2 treatment improves renal hemodynamic and kidney function and decreases oxidative stress of Wistar and SHR rats with an AKI episode. Furthermore, it also implies that pre-existing hypertension does not affect the beneficial effects of HBO2 preconditioning.
Subject(s)
Acute Kidney Injury/prevention & control , Hyperbaric Oxygenation , Ischemic Preconditioning/methods , Kidney/blood supply , Reperfusion Injury/prevention & control , Animals , Catalase/blood , Creatinine/blood , Male , Oxidative Stress , Phosphates/blood , Rats , Rats, Inbred SHR , Rats, Wistar , Superoxide Dismutase/blood , Urea/bloodABSTRACT
Renal ischemia/reperfusion injury is a common cause of acute kidney injury (AKI) and hypertension might contribute to the increased incidence of AKI. The purpose of this study was to investigate the effects of single and combined hyperbaric oxygen (HBO) preconditioning and NADPH oxidase inhibition on oxidative stress, kidney function and structure in spontaneously hypertensive rats (SHR) after renal ischemia reperfusion injury. HBO preconditioning was performed by exposing to pure oxygen (2.026 bar) twice a day for two consecutive days for 60 minutes, and 24h before AKI induction. For AKI induction, the right kidney was removed and ischemia was performed by clamping the left renal artery for 45 minutes. NADPH oxidase inhibition was induced by apocynin (40 mg/kg b.m., intravenously) 5 minutes before reperfusion. AKI significantly increased renal vascular resistance and reduced renal blood flow, which were significantly improved after apocynin treatment. Also, HBO preconditioning, with or without apocynin treatment showed improvement on renal hemodynamics. AKI significantly increased plasma creatinine, urea, phosphate levels and lipid peroxidation in plasma. Remarkable improvement, with decrease in creatinine, urea and phosphate levels was observed in all treated groups. HBO preconditioning, solitary or with apocynin treatment decreased lipid peroxidation in plasma caused by AKI induction. Also, combined with apocynin, it increased catalase activity and solitary, glutathione reductase enzyme activity in erythrocytes. While AKI induction significantly increased plasma KIM- 1 levels, HBO preconditioning, solitary or with apocynin decreased its levels. Considering renal morphology, significant morphological alterations present after AKI induction were significantly improved in all treated groups with reduced tubular dilatation, tubular necrosis in the cortico-medullary zone and PAS positive cast formation. Our results reveal that NADPH oxidase inhibition and hyperbaric oxygen preconditioning, with or without NADPH oxidase inhibition may have beneficial effects, but their protective role should be evaluated in further studies.
Subject(s)
Acetophenones/therapeutic use , Acute Kidney Injury/therapy , Enzyme Inhibitors/therapeutic use , Hyperbaric Oxygenation/methods , NADPH Oxidases/antagonists & inhibitors , Reperfusion Injury/therapy , Acute Kidney Injury/complications , Acute Kidney Injury/metabolism , Acute Kidney Injury/pathology , Animals , Male , Oxidative Stress/drug effects , Rats , Rats, Inbred SHR , Reperfusion Injury/etiology , Reperfusion Injury/metabolism , Reperfusion Injury/pathologyABSTRACT
BACKGROUND: Urtica dioica L. (Stinging nettle) has been used for centuries for the treatment of numerous health issues. PURPOSE: This study investigates the antioxidant capacity and the most abundant phenolic compounds of Urtica dioica L. leaf extract (UE), and its antihypertensive and antioxidative effects in vivo. STUDY DESIGN: Spontaneously hypertensive rats were supplemented with 10, 50, and 200 mg/kg/day of UE and 10 mg/kg/day of losartan during 4-week period. METHODS: In this study, HPLC analysis of UE was performed, as well as the determination of antioxidant capacity, superoxide radical scavenging activity, and metal chelating ability. Hemodynamic parameters were measured directly in anesthetized rats. Also, antioxidant enzyme activity and concentration in erythrocytes were determined, as well as systemic oxidative stress and plasma antioxidant status. RESULTS: UE showed higher ferric reducing antioxidant power and Trolox equivalent antioxidant capacity than BHT, but lower than vitamin C. Furthermore, UE showed good metal chelating ability, but weak superoxide radical scavenging activity. All three tested UE doses managed to reduce systolic and diastolic blood pressure, as well as cardiac index, and to improve the antioxidative defense by increasing the activity of superoxide dismutase and catalase, without changing the concentration of the enzymes. Moreover, UE supplementation increased plasma antioxidant capacity and reduced systemic oxidative stress. CONCLUSION: Chronic UE dietary supplementation had beneficial effects in the experimental model of essential hypertension.
Subject(s)
Antihypertensive Agents/pharmacology , Antioxidants/pharmacology , Blood Pressure/drug effects , Oxidative Stress/drug effects , Plant Extracts/pharmacology , Urtica dioica/chemistry , Animals , Male , Plant Leaves/chemistry , Rats , Rats, Inbred SHRABSTRACT
High blood pressure is the most powerful contributor to the cardiovascular morbidity and mortality, and inverse correlation between consumption of polyphenol-rich foods or beverages and incidence of cardiovascular diseases gains more importance. Reactive oxygen species plays an important role in the development of hypertension. We found that wild thyme (a spice plant, rich in polyphenolic compounds) induced a significant decrease of blood pressure and vascular resistance in hypertensive rats. The inverse correlation between vascular resistance and plasma heme oxygenase-1 suggests that endogenous vasodilator carbon monoxide generated by heme oxidation could account for this normalization of blood pressure. Next product of heme oxidation, bilirubin (a chain-breaking antioxidant that acts as a lipid peroxyl radical scavenger), becomes significantly increased after wild thyme treatment and induces the reduction of plasma lipid peroxidation in hypertensive, but not in normotensive rats. The obtained results promote wild thyme as useful supplement for cardiovascular interventions.