Grape seed proanthocyanidins ameliorates cadmium-induced renal injury and oxidative stress in experimental rats through the up-regulation of nuclear related factor 2 and antioxidant responsive elements

2015 ◽  
Vol 93 (3) ◽  
pp. 210-226 ◽  
Author(s):  
Bashir Nazima ◽  
Vaihundam Manoharan ◽  
Selvaraj Miltonprabu
Keyword(s):  
Oxidative Stress ◽  
Renal Injury ◽  
Caspase 3 ◽  
Grape Seed ◽  
Ionic Form ◽  
Related Factor ◽  
Enzymatic Antioxidants ◽  
Grape Seed Proanthocyanidins ◽  
Tnf Α ◽  
And Oxidative Stress

Cadmium (Cd) preferentially accumulates in the kidney, the major target for Cd-related toxicity. Cd-induced reactive oxygen species (ROS) have been considered crucial mediators for renal injury. The biologically significant ionic form of cadmium (Cd+) binds to many bio-molecules, and these interactions underlie the toxicity mechanisms of Cd. The present study was hypothesized to explore the protective effect of grape seed proanthocyanidins (GSP) on Cd-induced renal toxicity and to elucidate the potential mechanism. Male Wistar rats were treated with Cd as cadmium chloride (CdCl2, 5 mg·kg−1 bw, orally) and orally pre-administered with GSP (100 mg·kg−1 bw) 90 min before Cd intoxication for 4 weeks to evaluate renal damage of Cd and antioxidant potential of GSP. Serum renal function parameters (blood urea nitrogen and creatinine) levels in serum and urine, renal oxidative stress (lipid peroxidation, protein carbonylation, enzymatic, and non-enzymatic antioxidants), inflammatory (NF-κB p65, NO, TNF-α, IL-6), apoptotic (caspase-3, caspase-9, Bax, Bcl-2), membrane bound ATPases, and Nrf2 (HO-1, keap1, γ-GCS, and μ-GST) markers were evaluated in Cd-treated rats. Pretreatment with GSP revealed a significant improvement in renal oxidative stress markers in kidneys of Cd-treated rats. In addition, GSP treatment decreases the amount of iNOS, NF-κB, TNF-α, caspase-3, and Bax and increases the levels Bcl-2 protein expression. Similarly, mRNA and protein analyses substantiated that GSP treatment notably normalizes the renal expression of Nrf2/Keap1 and its downstream regulatory proteins in the Cd-treated rats. Histopathological and ultra-structural observations also demonstrated that GSP effectively protects the kidney from Cd-induced oxidative damage. These findings suggest that GSP ameliorates renal dysfunction and oxidative stress through the activation of Nrf2 pathway in Cd-intoxicated rats.

Grape seed proanthocyanidins prevent DOCA-salt hypertension-induced renal injury and its mechanisms in rats

2015 ◽  
Vol 6 (7) ◽  
pp. 2179-2186 ◽  
Author(s):  
Chao-zong Lan ◽  
Ling Ding ◽  
Yi-lin Su ◽  
Kun Guo ◽  
Li Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Renal Dysfunction ◽  
Renal Injury ◽  
Grape Seed ◽  
Deoxycorticosterone Acetate ◽  
Grape Seed Proanthocyanidins ◽  
Acetate Salt ◽  
Salt Hypertension

Renal dysfunction is one of the major effects of DOCA (deoxycorticosterone acetate)-salt hypertension and there is an increasing amount of evidence that oxidative stress damages the function of the kidney.

scholarly journals The molecular and biochemical insight view of grape seed proanthocyanidins in ameliorating cadmium-induced testes-toxicity in rat model: implication of PI3K/Akt/Nrf-2 signaling

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Nazima Bashir ◽  
Kalist Shagirtha ◽  
Vaikundam Manoharan ◽  
Selvaraj Miltonprabu
Keyword(s):  
Oxidative Stress ◽  
Protective Action ◽  
Grape Seed ◽  
Histological Changes ◽  
Grape Seed Proanthocyanidins ◽  
Protein Expressions ◽  
Male Wistar Rats ◽  
And Oxidative Stress ◽  
Enos Protein ◽  
Significant Increment

Abstract The present study aims to evaluate the protective effect of grape seed proanthocyanidins (GSP) on cadmium (Cd)-induced testicular apoptosis, inflammation, and oxidative stress in rats. A total of 24 male Wistar rats were divided into four groups, namely control, GSP (100 mg/kg BW), Cd (5 mg/kg BW), and Cd+GSP. Cd-treated rat testes exhibited a significant increment in oxidative stress mediated inflammation and apoptosis. Pre-administration of GSP exhibit significant protection against the apoptotic and inflammatory damages elicited by Cd and uphold the intercellular antioxidant status in testes. Histological changes were studied and the immunohistochemical staining for caspase 3, HSP70, and eNOS protein expressions were also analyzed to justify the protective action of GSP. Furthermore, GSP prevented DNA damage, and enhanced the expression of antioxidant responsive elements Nrf2/HO-1 by PI3K/Akt-dependent pathway. Therefore, our results suggest that GSP acts as a multipotent antioxidant entity against Cd-induced oxidative testicular toxicity in rats.

scholarly journals Grape Seed Proanthocyanidin Extract Alleviates AflatoxinB1-Induced Immunotoxicity and Oxidative Stress via Modulation of NF-κB and Nrf2 Signaling Pathways in Broilers

Toxins ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 23 ◽  
Author(s):  
Shahid Ali Rajput ◽  
Lvhui Sun ◽  
Ni-Ya Zhang ◽  
Mahmoud Mohamed Khalil ◽  
Zhao Ling ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathways ◽  
Broiler Chickens ◽  
Basal Diet ◽  
Grape Seed ◽  
Nuclear Factor ◽  
Tnf Α ◽  
Grape Seed Proanthocyanidin ◽  
Ifn Γ ◽  
And Oxidative Stress

Aflatoxin B1 (AFB1) is a widely spread mycotoxin contaminates food and feed, causing severe oxidative stress damages and immunotoxicity. Grape seed proanthocyanidin (GSPE), a natural antioxidant with wide range of pharmacological and medicinal properties. The goal of the present study was to investigate the protective effects of GSPE against AFB1-induced immunotoxicity and oxidative stress via NF-κB and Nrf2 signaling pathways in broiler chickens. For the experiment, 240 one-day old Cobb chicks were allocated into four dietary treatment groups of six replicates (10 birds per replicate): 1. Basal diet (control); 2. Basal diet + AFB1 1mg/kg contaminated corn (AFB1); 3. Basal diet + GSPE 250 mg/kg (GSPE); 4. Basal diet + AFB1 1 mg/kg + GSPE 250 mg/kg (AFB1 + GSPE). The results showed that GSPE significantly decreased serum inflammatory cytokines TNF-α, IFN-γ, IL-1β, IL-10, and IL-6 induced by AFB1. Similarly, GSPE + AFB1 treated group revealed a significant decrease in mRNA expressions of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β, and IL-6) in the splenic tissue compared to the AFB1 treatment group. In addition, western blotting results manifested that GSPE treatment normalized the phosphorylation of nuclear factor kappa B (p65) and the degradation of IκBα protein induced by AFB1. Furthermore, GSPE enhanced the antioxidant defense system through activating the nuclear factor-erythroid-2-related factor (Nrf2) signaling pathway. The mRNA and protein expression level of Nrf2 and its down streaming associated genes were noted up-regulated by the addition of GSPE, and down-regulated in the AFB1 group. Taken together, GSPE alleviates AFB1-induced immunotoxicity and oxidative damage by inhibiting the NF-κB and activating the Nrf2 signaling pathways in broiler chickens. Conclusively, our results suggest that GSPE could be considered as a potential natural agent for the prevention of AFB1-induced immunotoxicity and oxidative damage.

Inhibition of microRNA-155 Alleviates Neurological Dysfunction Following Transient Global Ischemia and Contribution of Neuroinflammation and Oxidative Stress in the Hippocampus

2020 ◽  
Vol 25 (40) ◽  
pp. 4310-4317 ◽  
Author(s):  
Lichao Sun ◽  
Shouqin Ji ◽  
Jihong Xing
Keyword(s):  
Oxidative Stress ◽  
Brain Edema ◽  
Severity Score ◽  
Global Ischemia ◽  
Signal Pathways ◽  
Neurological Severity Score ◽  
Tnf Α ◽  
Transient Global Ischemia ◽  
And Oxidative Stress

Background/Aims: Central pro-inflammatory cytokine (PIC) signal is involved in neurological deficits after transient global ischemia induced by cardiac arrest (CA). The present study was to examine the role of microRNA- 155 (miR-155) in regulating IL-1β, IL-6 and TNF-α in the hippocampus of rats with induction of CA. We further examined the levels of products of oxidative stress 8-isoprostaglandin F2α (8-iso PGF2α, indication of oxidative stress); and 8-hydroxy-2’-deoxyguanosine (8-OHdG, indication of protein oxidation) after cerebral inhibition of miR-155. Methods: CA was induced by asphyxia and followed by cardiopulmonary resuscitation in rats. ELISA and western blot analysis were used to determine the levels of PICs and products of oxidative stress; and the protein expression of NADPH oxidase (NOXs) in the hippocampus. In addition, neurological severity score and brain edema were examined to assess neurological functions. Results: We observed amplification of IL-1β, IL-6 and TNF-α along with 8-iso PGF2α and 8-OHdG in the hippocampus of CA rats. Cerebral administration of miR-155 inhibitor diminished upregulation of PICs in the hippocampus. This also attenuated products of oxidative stress and upregulation of NOX4. Notably, inhibition of miR-155 improved neurological severity score and brain edema and this was linked to signal pathways of PIC and oxidative stress. Conclusion: We showed the significant role of blocking miR-155 signal in improving the neurological function in CA rats likely via inhibition of signal pathways of neuroinflammation and oxidative stress, suggesting that miR-155 may be a target in preventing and/or alleviating development of the impaired neurological functions during CA-evoked global cerebral ischemia.

Neuroprotection of chromobox 7 knockout in the mouse after cerebral ischemia-reperfusion injury via nuclear factor E2-related factor 2/hemeoxygenase-1 signaling pathway

2021 ◽  
pp. 096032712110361
Author(s):  
Hai-Tao Zhang ◽  
Xi-Zeng Wang ◽  
Qing-Mei Zhang ◽  
Han Zhao
Keyword(s):  
Oxidative Stress ◽  
Cerebral Ischemia ◽  
Infarct Size ◽  
Water Content ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion ◽  
Related Factor ◽  
Nuclear Factor ◽  
Cerebral Ischemia Reperfusion ◽  
And Oxidative Stress

Objective To explore the mechanism of chromobox 7 (CBX7)-mediated nuclear factor E2-related factor 2 (Nrf2)/hemeoxygenase-1 (HO-1) signaling pathway in the cerebral ischemia/reperfusion (I/R) injury. Methods The experimental wild-type (WT) and CBX7-/- mice were used to establish cerebral I/R models using the middle cerebral artery occlusion (MCAO) surgery to determine CBX7 levels at different time points after MCAO injury. For all mice, neurological behavior, infarct size, water content, and oxidative stress–related indicators were determined, and transferase (TdT)-mediated dUTP-biotin nick-end labeling (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL)) staining method was employed to observe cell apoptosis, while Western blot to measure the expression of CBX7 and Nrf/HO-1 pathway-related proteins. Results At 6 h, 12 h, 24 h, 3 days, and 7 days after mice with MCAO, CBX7 expression was gradually up-regulated and the peak level was reached at 24 h. Mice in the WT + MCAO group had increased infarct size, with significant increases in the modified neurological severity scores and water content in the brain, as well as the quantity of TUNEL-positive cells. For the oxidative stress-indicators, an increase was seen in the content of MDA (malondial dehyde), but the activity of SOD (superoxide dismutase) and content of GSH-PX (glutathione peroxidase) and CAT (catalase) were decreased; meanwhile, the protein expression of CBX7, HO-1, and nuclear Nrf2 was up-regulated, while the cytoplasmic Nrf2 was down-regulated. Moreover, CBX7 knockout attenuated I/R injury in mice. Conclusion Knockout of CBX7 may protect mice from cerebral I/R injury by reducing cell apoptosis and oxidative stress, possibly via activating the Nrf2/HO-1 pathway.

Febuxostat Attenuates the Progression of Periodontitis in Rats

Pharmacology ◽  
2021 ◽  
pp. 1-11
Author(s):  
Naseratun Nessa ◽  
Miyuki Kobara ◽  
Hiroe Toba ◽  
Tetsuya Adachi ◽  
Toshiro Yamamoto ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Bone Resorption ◽  
Alveolar Bone ◽  
Alveolar Bone Loss ◽  
Gingival Tissue ◽  
Systemic Effects ◽  
Rt Pcr ◽  
Tnf Α ◽  
And Oxidative Stress

Introduction: Periodontitis is a lifestyle-related disease that is characterized by chronic inflammation in gingival tissue. Febuxostat, a xanthine oxidase inhibitor, exerts anti-inflammatory and antioxidant effects. Objective: The present study investigated the effects of febuxostat on periodontitis in a rat model. Methods: Male Wistar rats were divided into 3 groups: control, periodontitis, and febuxostat-treated periodontitis groups. Periodontitis was induced by placing a ligature wire around the 2nd maxillary molar and the administration of febuxostat (5 mg/kg/day) was then initiated. After 4 weeks, alveolar bone loss was assessed by micro-computed tomography and methylene blue staining. The expression of osteoprotegerin (OPG), a bone resorption inhibitor, was detected by quantitative RT-PCR and immunological staining, and the number of osteoclasts in gingival tissue was assessed by tartrate-resistant acid phosphatase staining. The mRNA and protein expression levels of the proinflammatory cytokines, tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β), in gingival tissue were measured using quantitative RT-PCR and immunological staining. Oxidative stress in gingival tissue was evaluated by the expression of 4-hydroxy-2-nonenal (4-HNE), and 8-hydroxy-2-deoxyguanosine (8-OHdG). To clarify the systemic effects of periodontitis, blood pressure and glucose tolerance were examined. Results: In rats with periodontitis, alveolar bone resorption was associated with reductions in OPG and increases in osteoclast numbers. The gingival expression of TNF-α, IL-1β, 4-HNE, and 8-OHdG was up-regulated in rats with periodontitis. Febuxostat significantly reduced alveolar bone loss, proinflammatory cytokine levels, and oxidative stress. It also attenuated periodontitis-induced glucose intolerance and blood pressure elevations. Conclusion: Febuxostat prevented the progression of periodontitis and associated systemic effects by inhibiting proinflammatory mediators and oxidative stress.

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