scholarly journals Hyperhomocysteinaemia induced by dietary folate restriction causes kidney oxidative stress in rats

2005 ◽  
Vol 94 (2) ◽  
pp. 204-210 ◽  
Author(s):  
Nieves Díez ◽  
Raquel Pérez ◽  
Verónica Hurtado ◽  
Santiago Santidrián

Diet is the most common cause of mild hyperhomocysteinaemia (HHcy), which occurs in approximately 5–7 % of the general population. Since HHcy causes endothelial damage by oxidative stress in different organs, the present study was designed to examine whether HHcy might be involved in renal oxidative stress. Twenty-five male Wistar rats were randomly divided into two groups: one (n13) was fedad libituma folate-free diet (FF) and the other (n12) was fed the same diet supplemented with folic acid (control, CO). After 8 weeks the animals were killed and kidneys removed. Malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were measured in plasma and kidney homogenates. Renal tissue sections were analysed by indirect immunostaining with the primary antibody against oxidatively modified LDL receptor (LOX-1). A marked HHcy was confirmed in the FF group. As compared with CO animals, MDA levels in plasma and kidney homogenate were significantly higher in FF rats (P<0·05). Similarly, renal GPx and SOD activities were significantly higher in the FF group (P<0·001). No differences were found in LOX-1 immunohistochemical expression, which in the two groups was displayed in tubular cells. The present study provides evidence that HHcy does produce renal oxidative stress mediated by lipid peroxidation, and that the increased kidney MDA displayed by FF animals may enhance kidney antioxidant activity and thereby attenuate both kidney damage and expression of LOX-1.

2020 ◽  
Vol 13 (4) ◽  
pp. 342-352 ◽  
Author(s):  
Vipin K. Verma ◽  
Salma Malik ◽  
Ekta Mutneja ◽  
Anil K. Sahu ◽  
Kumari Rupashi ◽  
...  

Background: The activation of Nrf2/HO-1 pathway has been shown to protect against cisplatin- induced nephrotoxicity by reducing oxidative stress. Berberine (Ber), an isoquinoline alkaloid, has demonstrated antioxidant, anti-inflammatory and anti-apoptotic activities in various experimental models. Aim: To check the effect of Ber on cisplatin-induced nephrotoxicity and to explore the involved mechanism. Methods: Adult male Wistar rats were divided into 6 groups: Normal, cisplatin-control, treatment groups and per se group. Normal saline and Ber (20, 40 and 80 mg/kg; p.o.) was administered to rats for 10 days. A single intraperitoneal injection of cisplatin (8 mg/kg) was injected on 7th day to induced nephrotoxicity. On 10th day, rats were sacrificed, the kidney was removed and stored for the estimation of various parameters. Results: As compared to cisplatin-control group, Ber pretreatment improved renal function system and preserved renal architecture. It also diminished oxidative stress by upregulating the expression of Nrf2/HO-1 proteins. In addition, Ber attenuated the cisplatin mediated inflammation and apoptosis. Furthermore, it also reduced the phosphorylation of p38/JNK and PARP/Beclin-1 expression in the kidney. Conclusion: Ber attenuated renal injury by activating Nrf2/HO-1 and inhibiting JNK/p38MAPKs/ PARP/Beclin-1 expression which prevented oxidative stress, inflammation, apoptosis and autophagy in renal tissue.


2012 ◽  
Vol 303 (4) ◽  
pp. F576-F583 ◽  
Author(s):  
Silvia Kelsen ◽  
Xiaochen He ◽  
Alejandro R. Chade

Renal artery stenosis (RAS), the main cause of chronic renovascular disease (RVD), is associated with significant oxidative stress. Chronic RVD induces renal injury partly by promoting renal microvascular (MV) damage and blunting MV repair in the stenotic kidney. We tested the hypothesis that superoxide anion plays a pivotal role in MV dysfunction, reduction of MV density, and progression of renal injury in the stenotic kidney. RAS was induced in 14 domestic pigs and observed for 6 wk. Seven RAS pigs were chronically treated with the superoxide dismutase mimetic tempol (RAS+T) to reduce oxidative stress. Single-kidney hemodynamics and function were quantified in vivo using multidetector computer tomography (CT) and renal MV density was quantified ex vivo using micro-CT. Expression of angiogenic, inflammatory, and apoptotic factors was measured in renal tissue, and renal apoptosis and fibrosis were quantified in tissue sections. The degree of RAS and blood pressure were similarly increased in RAS and RAS+T. Renal blood flow (RBF) and glomerular filtration rate (GFR) were reduced in the stenotic kidney (280.1 ± 36.8 and 34.2 ± 3.1 ml/min, P < 0.05 vs. control). RAS+T kidneys showed preserved GFR (58.5 ± 6.3 ml/min, P = not significant vs. control) but a similar decreases in RBF (293.6 ± 85.2 ml/min) and further decreases in MV density compared with RAS. These changes were accompanied by blunted angiogenic signaling and increased apoptosis and fibrosis in the stenotic kidney of RAS+T compared with RAS. The current study shows that tempol administration provided limited protection to the stenotic kidney. Despite preserved GFR, renal perfusion was not improved by tempol, and MV density was further reduced compared with untreated RAS, associated with increased renal apoptosis and fibrosis. These results suggest that a tight balance of the renal redox status is necessary for a normal MV repair response to injury, at least at the early stage of RVD, and raise caution regarding antioxidant strategies in RAS.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Maya P. Radeva-Ilieva ◽  
Kaloyan D. Georgiev ◽  
Nadezhda R. Hvarchanova ◽  
Stanila S. Stoeva ◽  
Iliya J. Slavov ◽  
...  

Doxorubicin is an anthracycline antibiotic that is used for the treatment of various types of cancer. However, its clinical usage is limited due to its potential life-threatening adverse effects, such as cardio- and nephrotoxicities. Nonetheless, simultaneous administration of doxorubicin and antioxidants, such as those found in green tea leaves, could reduce cardiac and renal tissue damage caused by oxidative stress. The methylxanthine fraction isolated from Bancha tea leaves were tested in vitro for its antioxidant activity and in vivo for its organoprotective properties against doxorubicin-induced cardio- and nephrotoxicities in a rat model. The in vivo study was conducted on male Wistar rats divided into 6 groups. Methylxanthines were administered at high (5 mg/kg body weight) and low (1 mg/kg body weight) doses, while doxorubicin was administered at a cumulative dose of 20 mg/kg body weight. Serum creatinine, uric acid, and urea concentrations, as well as serum enzyme levels (creatinine kinase (CK), creatinine kinase MB fraction (CK-MB), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH)) and electrolytes (Na+, K+, and Cl-), were analysed. In addition, histological analysis was performed to assess cardiac and renal tissue damage. The concomitant administration of Bancha methylxanthines and doxorubicin showed a dose-dependent reduction in the serum biochemical parameters, indicating a decrease in the cardiac and renal tissue damage caused by the antibiotic. Histological analysis showed that pretreatment with methylxanthines at the dose of 5 mg/kg resulted in an almost normal myocardial structure and a significant decrease in the morphological kidney changes caused by doxorubicin exposure compared with the group that received doxorubicin alone. The putative mechanism is most likely related to a reduction in the oxidative stress caused by doxorubicin.


2021 ◽  
Vol 67 (4) ◽  
pp. 338-346
Author(s):  
V.I. Zvyagina ◽  
E.S. Belskikh

Hyperhomocysteinemia is a risk factor for many diseases, including reproductive disorders in men. L-carnitine is used in medical practice to correct impaired bioenergetic conditions; in patients with idiopathic forms of infertility its effects are associated with improvement of the sperm parameters. However, the effect of exogenous L-carnitine on the level of homocysteine in the gonadal tissues, as a risk factor for impaired fertility, has not been investigated yet. The aim of this study was to investigate activity of bioenergetic enzymes in the epididymal mitochondrial fraction, the dynamics of changes in the cytoplasmic and mitochondrial lactate levels and LDH activity, the total carnitine content, as well as the oxidative status of these cells under conditions of oxidative stress caused by hyperhomocysteinemia, and to assess the effect of carnitine chloride on these parameters under conditions of methionine administration to male Wistar rats. Methionine administration to animals for three weeks at a dose of 3 g/kg, resulted in development of the severe forms of hyperhomocysteinemia with serum homocysteine concentrations exceeding 100 μmol/L. This was accompanied by a decrease in the activity of enzymes involved in the bioenergetic processes of the cell: tissue respiration (succinate dehydrogenase) and oxidative phosphorylation (H+-ATPase) in the epididymal head and tail. The change in lactate metabolism included an increase in its level in both the mitochondrial and cytoplasmic fractions of the epididymal head and mitochondria of the epididymal tail, and also simultaneous statistically significant decrease in LDH activity in the mitochondria and cytoplasm of the epididymal head. In male rats with severe hyperhomocysteinemia, an increase in the activity of mitochondrial SOD accompanied by an increase in the carbonylation of mitochondrial proteins in the head and tail of the epididymis was noted. Modeling of hyperhomocysteinemia under conditions of carnitine chloride of administration led to different reactions of the cells of the studied tissues assayed in the epididymal head and tail homogenate. In the epididymal head, carnitine chloride promoted an increase in the mitochondrial lactate concentration and a decrease in the cytoplasmic lactate concentration, as well as an increase in the LDH activity associated with the mitochondrial fraction. These changes were accompanied by an increase in the activity of H+-ATPase in the epididymal, thus suggesting that carnitine chloride stimulated lactate transport of into the mitochondria and its use as an energy substrate under conditions of oxidative stress caused by hyperhomocysteinemia. In the tail tissues, the changes were protective in nature and were associated with a decrease in the formation of oxidatively modified proteins.


2021 ◽  
Vol 11 (10) ◽  
pp. 4548
Author(s):  
Ahmed Z. Alanazi ◽  
Mohamed Mohany ◽  
Fawaz Alasmari ◽  
Ramzi A. A. Mothana ◽  
Abdulaziz O. A. Alshehri ◽  
...  

In traditional Yemeni medicine, various preparations of Loranthus regularis (L. regularis), such as powder, decoctions and infusions are commonly used to treat diabetes, kidney stone formations and inflammation. In the present study, we evaluated the antinephrotoxic effects of L. regularis extract in experimentally-induced diabetes in male Wistar rats. A single dose (60 mg/kg/day) of Streptozotocin (STZ) was used to induce type 1 diabetes. Animals were then treated for four weeks with L. regularis extract (150 or 300 mg/kg/day) by oral gavage. Renal and blood samples were subsequently harvested. Several biochemical indices, oxidative stress and inflammatory markers were assessed. Additionally, histological alterations in the renal tissue were examined. Serum glucose levels were significantly (p < 0.01) lowered while insulin levels were enhanced in L. regularis-treated diabetic animals. The increased renal markers in diabetic rats were decreased by L. regularis treatment. Serum elevated lipid profiles were markedly decreased by the plant extract. The serum and renal cytokines that were significantly increased (p < 0.001) by STZ were diminished by L. regularis treatment. Finally, renal tissue antioxidant enzymatic activity was enhanced with L. regularis treatment. Taken together, the data here indicate that L. regularis possesses therapeutic ability to reduce the development of diabetic nephropathy (DN) by minimizing oxidative injury and inflammation.


Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 335
Author(s):  
Estefanía Bravo-Sánchez ◽  
Donovan Peña-Montes ◽  
Sarai Sánchez-Duarte ◽  
Alfredo Saavedra-Molina ◽  
Elizabeth Sánchez-Duarte ◽  
...  

Diabetes mellitus (DM) constitutes one of the public health problems today. It is characterized by hyperglycemia through a defect in the β-cells function and/or decreased insulin sensitivity. Apocynin has been tasted acting directly as an NADPH oxidase inhibitor and reactive oxygen species (ROS) scavenger, exhibiting beneficial effects against diabetic complications. Hence, the present study’s goal was to dissect the possible mechanisms by which apocynin could mediate its cardioprotective effect against DM-induced oxidative stress. Male Wistar rats were assigned into 4 groups: Control (C), control + apocynin (C+A), diabetes (D), diabetes + apocynin (D+A). DM was induced with streptozotocin. Apocynin treatment (3 mg/kg/day) was applied for 5 weeks. Treatment significantly decreased blood glucose levels and insulin resistance in diabetic rats. In cardiac tissue, ROS levels were higher, and catalase enzyme activity was reduced in the D group compared to the C group; the apocynin treatment significantly attenuated these responses. In heart mitochondria, Complexes I and II of the electron transport chain (ETC) were significantly enhanced in the D+A group. Total glutathione, the level of reduced glutathione (GSH) and the GSH/ oxidized glutathione (GSSG) ratio were increased in the D+A group. Superoxide dismutase (SOD) and the glutathione peroxidase (GSH-Px) activities were without change. Apocynin enhances glucose uptake and insulin sensitivity, preserving the antioxidant defense and mitochondrial function.


Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 630 ◽  
Author(s):  
Annalisa Noce ◽  
Manuela Di Lauro ◽  
Francesca Di Daniele ◽  
Anna Pietroboni Zaitseva ◽  
Giulia Marrone ◽  
...  

Metabolic syndrome (MetS) is a clinical manifestation characterized by a plethora of comorbidities, including hyperglycemia, abdominal obesity, arterial hypertension, and dyslipidemia. All MetS comorbidities participate to induce a low-grade inflammation state and oxidative stress, typical of this syndrome. MetS is related to an increased risk of cardiovascular diseases and early death, with an important impact on health-care costs. For its clinic management a poly-pharmaceutical therapy is often required, but this can cause side effects and reduce the patient’s compliance. For this reason, finding a valid and alternative therapeutic strategy, natural and free of side effects, could represent a useful tool in the fight the MetS. In this context, the use of functional foods, and the assumption of natural bioactive compounds (NBCs), could exert beneficial effects on body weight, blood pressure and glucose metabolism control, on endothelial damage, on the improvement of lipid profile, on the inflammatory state, and on oxidative stress. This review focuses on the possible beneficial role of NBCs in the prevention and in the clinical management of MetS and its comorbidities.


2001 ◽  
Vol 1 (1) ◽  
pp. 9-12 ◽  
Author(s):  
S.S. Signorelli ◽  
S. Neri ◽  
L. Di Pino ◽  
M.P. Costa ◽  
G. Pennisi ◽  
...  

2004 ◽  
Vol 101 (5) ◽  
pp. 822-825 ◽  
Author(s):  
Dunyue Lu ◽  
Asim Mahmood ◽  
Changsheng Qu ◽  
Anton Goussev ◽  
Mei Lu ◽  
...  

Object. Atorvastatin, a β-hydroxy-β-methylglutaryl coenzyme A reductase inhibitor, has pleiotropic effects such as improving thrombogenic profile, promoting angiogenesis, and reducing inflammatory responses and has shown promise in enhancing neurological functional improvement and promoting neuroplasticity in animal models of traumatic brain injury (TBI), stroke, and intracranial hemorrhage. The authors tested the effect of atorvastatin on intracranial hematoma after TBI. Methods. Male Wistar rats were subjected to controlled cortical impact, and atorvastatin (1 mg/kg) was orally administered 1 day after TBI and daily for 7 days thereafter. Rats were killed at 1, 8, and 15 days post-TBI. The temporal profile of intraparenchymal hematoma was measured on brain tissue sections by using a MicroComputer Imaging Device and light microscopy. Conclusions. Data in this study showed that intraparenchymal and intraventricular hemorrhages are present 1 day after TBI and are absorbed at 15 days after TBI. Furthermore, atorvastatin reduces the volume of intracranial hematoma 8 days after TBI.


Life Sciences ◽  
2006 ◽  
Vol 79 (23) ◽  
pp. 2187-2193 ◽  
Author(s):  
Maria H.V.M. Jacob ◽  
Mauro R.N. Pontes ◽  
Alex S.R. Araújo ◽  
Jaqueline Barp ◽  
Maria C. Irigoyen ◽  
...  

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