scholarly journals Raspberry Increases Expression of Antioxidant Enzymes in the Kidney of Angiotensin II-Treated Rats

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 341-341
Author(s):  
Lena MT Lear ◽  
Rami Najjar ◽  
Maureen Meister ◽  
Jessica Danh ◽  
Desiree Wanders ◽  
...  

Abstract Objectives To examine whether dietary supplementation with raspberries attenuates angiotensin (Ang) II-induced oxidative stress in the kidneys of rats. Methods Eight-week-old male Sprague-Dawley rats were fed an AIN-93M diet (control and Ang II groups) or AIN-93M diet supplemented with 10% w/w freeze-dried raspberry (RB + Ang II) for seven weeks. At week 4, rats were implanted with subcutaneous osmotic minipumps that delivered 0.9% saline (control) or Ang II (270 ng/kg body weight/day) for an additional three weeks. Protein expression of antioxidant enzymes, such as glutathione peroxidase 1 (GP × 1) and NADPH quinone dehydrogenase 1 (NQO1), as well as ERK1/2 phosphorylation were assessed by western blot in the kidneys. Results were analyzed using one-way ANOVA followed by Tukey-Kramer post hoc test. Data were normalized to control and are expressed as mean ± standard deviation. Results The expression of the antioxidant enzyme GP × 1 was significantly increased with raspberry supplementation (1.33 ± 0.24-fold, n = 9) in comparison to control (1.00 ± 0.18-fold, n = 9, P = 0.009) and Ang II alone (0.93 ± 0.24-fold, n = 9, P = 0.002). The expression of the antioxidant enzyme NQO1 was significantly increased with raspberry supplementation (2.10 ± 0.74-fold, n = 9) in comparison to control (1.00 ± 0.44-fold, n = 9, P = 0.0002) and Ang II alone (0.74 ± 0.16-fold, n = 9, P < 0.0001). Although not significantly, Ang II induced an increase in ERK1/2 phosphorylation in comparison to control (1.66 ± 0.45 vs 1.00 ± 0.88-fold, n = 5, P = 0.22). Nonetheless, raspberry supplementation (0.62 ± 0.22-fold, n = 5, P = 0.02) was able to attenuate ERK1/2 phosphorylation in comparison to Ang II alone. Conclusions Our findings indicate that supplementation with raspberry has the potential to significantly increase the expression of antioxidant enzymes in a model of Ang II-induced oxidative stress. Future work will focus on elucidating the mechanism through which raspberries elicit their action in the kidneys. Funding Sources This work was supported by the Agriculture and Food Research Initiative (grant no. 2019–67,017-29,257/project accession no. 1,018,642) from the USDA National Institute of Food and Agriculture.

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 298-298
Author(s):  
Jasmynne Blacks ◽  
Ferdinand Althammer ◽  
Rami Najjar ◽  
Maureen Meister ◽  
Jessica Dahn ◽  
...  

Abstract Objectives To examine whether raspberry (RB) attenuates oxidative stress induced by angiotensin (Ang) II in the subfornical organ (SFO) of the brain in rats. Methods Male Sprague-Dawley rats were fed an AIN-93M diet with or without 10% w/w freeze-dried RB powder for seven weeks. At week 4, rats were implanted with subcutaneous osmotic minipumps that delivered 0.9% saline (Control) or Ang II (270 ng/kg body weight/day) for another three weeks. Brain region-specific tissue punches were collected from flash-frozen sections containing the SFO. NADPH oxidase (NOX) 2 and 4 and superoxide dismutase (SOD) 1 and 2 were measured in SFO using western blot. Results were analyzed using one-way ANOVA followed by Tukey post hoc test. Data were normalized to control and are expressed as means ± standard deviation. Results Ang II significantly increased NOX2 expression compared to control (1.24 ± 0.1, n = 5, vs 1.00 ± 0.07-fold, n = 3, P = 0.009) while RB supplementation significantly attenuated Ang II-induced increases in NOX2 (0.91 ± 0.05-fold, n = 4; P = 0.0006). Ang II also increased NOX4 expression compared to control (2.11 ± 1.2, n = 9, vs 0.98 ± 0.4-fold, n = 6, P = 0.04), but RB supplementation did not significantly attenuate this effect (1.30 ± 0.36-fold, n = 10, P = 0.11). RB increased expression of SOD1 (1.52 ± 0.20-fold, n = 4) compared to control (1.00 ± 0.15-fold, n = 3, P = 0.009) and Ang II alone (1.08 ± 0.16-fold, n = 5, P = 0.01). On the other hand, Ang II treatment decreased SOD2 expression compared to control (0.62 ± 0.05, n = 5, vs 1.00 ± 0.09-fold, n = 3, P = 0.0001), but the RB supplementation did not prevent this effect (0.72 ± 0.07-fold, n = 4, P = 0.16). Conclusions Our findings suggest that RB supplementation decreases Ang II-induced oxidative stress in the SFO by decreasing NOX2 and increasing SOD1 expression. Future investigations are warranted to elucidate the effects of RB on oxidative stress pathways in the SFO. Funding Sources This work was supported by the Agriculture and Food Research Initiative (grant no. 2019–67,017-29,257/project accession no. 1,018,642) from the USDA National Institute of Food and Agriculture.


2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 351-351
Author(s):  
Rami Najjar ◽  
Maureen Meister ◽  
Jessica Danh ◽  
Lena MT Lear ◽  
Justina Kim ◽  
...  

Abstract Objectives To determine whether raspberry consumption mitigates cardiac oxidative stress induced by angiotensin (Ang) II in rats. Methods Eight-week-old male Sprague-Dawley rats were fed AIN-93M (4% corn oil) diets with or without a 10% w/w raspberry freeze-dried powder for seven weeks. At week 4, rats were implanted with subcutaneous osmotic minipumps that delivered 0.9% saline (control) or Ang II (270 ng/kg body weight/day). At week 7, hearts were excised for protein analysis via western blot. Protein expression of NRF2 and its transcriptional products, HO-1 and NQO1, were quantified in the left ventricle. Data are normalized to control and presented as mean ± standard deviation. Results were analyzed with one-way ANOVA followed by Tukey post hoc test if data were normally distributed. Otherwise, non-parametric Kruskal-Wallis test was conducted. Results The expression of the antioxidant transcription factor NRF2 was significantly increased by raspberry consumption compared with Ang II alone (2.41 ± 0.62, n = 5 vs 1.31 ± 0.20-fold, n = 5, P = 0.002) and compared to control (1.00 ± 0.19-fold, n = 5, P = 0.0003). Additionally, the expression of NRF2 transcriptional product NQO1 was significantly increased by raspberry consumption compared to control (1.70 ± 0.52, n = 5 vs 1.00 ± 0.41-fold, n = 5, P = 0.05) but not compared to Ang II (1.30 ± 0.25-fold, n = 5, P = 0.3). Lastly, HO-1 was significantly increased in rats consuming raspberries compared to control (3.04 ± 1.80, n = 5 vs 1.00 ± 0.23-fold, n = 5, P = 0.02), but not compared to Ang II alone (1.92 ± 1.06-fold, n = 5, P = 0.8). Conclusions Raspberries directly increase NRF2 and its transcriptional products in the hearts of rats infused with Ang II. These findings may translate to cardio-protection from neurohumoral insult due to reduced oxidative stress and increased endogenous antioxidant enzyme activity. Funding Sources This work was supported by the Agriculture and Food Research Initiative (grant no. 2019–67,017-29,257/project accession no. 1,018,642) from the USDA National Institute of Food and Agriculture.


2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 347-347
Author(s):  
Maureen Meister ◽  
Rami Najjar ◽  
Jessica Danh ◽  
Lena MT Lear ◽  
Justina Kim ◽  
...  

Abstract Objectives To determine whether a diet supplemented with red raspberry (RB) is effective at reducing angiotensin (Ang) II-induced oxidative stress in the lungs of Sprague Dawley (SD) rats. Methods Eight-week-old male SD rats were fed an AIN-93M diet alone (control and Ang II) or supplemented with 10% w/w freeze-dried RB powder for a total of seven weeks. At week 4, SD rats were implanted with subcutaneous osmotic minipumps for delivery of 0.9% saline (control) or Ang II (270 ng/kg body weight/day). Following 3 weeks of infusion, rats were sacrificed, and lungs were collected for analysis. Protein expression of the pro-oxidant enzyme, NADPH oxidase (NOX) 4, and antioxidant enzymes superoxide dismutase 1 (SOD1), catalase, heme oxygenase-1 (HO-1), and NADPH quinone dehydrogenase 1 (NQO1) were assessed by western blot. Results were analyzed by one-way ANOVA followed by Tukey post-hoc test. Results were normalized to control and presented as means ± standard deviation. Results RB supplementation significantly increased the expression of antioxidant enzymes, including, SOD1 (1.34 ± 0.16, n = 5, vs 1.11 ± 0.13-fold, n = 5, P = 0.04) and catalase (1.50 ± 0.28, n = 5, vs 0.79 ± 0.20-fold, n = 5, P = 0.008), when compared to Ang II alone. Compared to control, however, RB significantly increased SOD1 (1.00 ± 0.05-fold, n = 4, P = 0.004) while catalase did not (1.00 ± 0.40, n = 4, P = 0.07). Similarly, HO-1 (1.66 ± 0.82, n = 5, vs 0.75 ± 0.13-fold, n = 4, P = 0.046) and NQO1 (2.13 ± 0.19, n = 4, vs 1.26 ± 0.14-fold, n = 5, P < 0.0001) were greater in the RB supplemented rats in comparison to Ang II alone. Additionally, RB significantly increased NQO1 (1.00 ± 0.16, n = 4, P < 0.0001) but not HO-1 (1.00 ± 0.43-fold, n = 4, P = 0.22) when compared to control. RB supplementation also decreased the expression of NOX4 (0.77 ± 0.38, n = 5, vs 1.41 ± 0.30-fold, n = 5, P = 0.02) in comparison to Ang II alone. Conclusions Our results suggest the potential for red raspberries to decrease oxidative stress within the lung tissue. As investigations into whole food dietary treatments in lung conditions are essentially non-existent, future work will aim to determine the potential for raspberries to serve as a complementary therapy in these conditions. Funding Sources This work was funded by the Agriculture and Food Research Initiative (grant no. 2019–67,017-29,257/project accession no. 1,018,642) from the USDA National Institute of Food and Agriculture.


2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 334-334
Author(s):  
Justina Kim ◽  
Maureen Meister ◽  
Rami Najjar ◽  
Jessica Dahn ◽  
Lena MT Lear ◽  
...  

Abstract Objectives Angiotensin (Ang) II induces inflammation in a number of tissues. Inflammation contribute to the development of hypertension and cardiovascular diseases. Thus, the objective of this study was to examine the effects of raspberry consumption on markers of inflammation in the liver of rats-infused with Ang II. Methods Male Sprague-Dawley rats (8-week-old) were fed either an AIN-93M diet alone or supplemented with 10% w/w freeze-dried raspberry powder for seven weeks. At week 4, the animals were subcutaneously implanted with osmotic minipumps, delivering 0.9% saline (control) or Ang II (270 ng/kg body weight/day). Diet and treatment were continued for three additional weeks. Hepatic expression of inflammatory cytokines interleukin (IL)-6 and IL-1β were evaluated by western blot. Results were analyzed by one-way ANOVA followed by Tukey post hoc test. Data were normalized to control and are expressed as means ± standard deviation. Results Ang II increased liver expression of IL-6 (1.73 ± 0.12, n = 5, vs 1.00 ± 0.17-fold, n = 5, P = 0.009) while supplementation with raspberry attenuated this effect (1.10 ± 0.14-fold, n = 5, P = 0.021). In contrast, no significant differences were observed in the expression of IL-1 β among groups. Conclusions Raspberry supplementation attenuated Ang II-induced increases in IL-6 expression in the liver. Further investigation is needed to elucidate the effects of raspberry supplementation on Ang II-induced inflammation in the liver. Funding Sources This work was supported by the Agriculture and Food Research Initiative (grant no. 2019–67,017-29,257/project accession no. 1,018,642) from the USDA National Institute of Food and Agriculture.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Rafaela Feresin ◽  
Rami Najjar ◽  
Christy Simecka ◽  
Shengyu Mu

Abstract Objectives To examine whether diet supplementation with blackberry or raspberry attenuate angiotensin (Ang) II-induced increase in blood pressure (BP) and decrease oxidative stress in the kidneys of mice. Methods Twelve-week male C57BL/6 J mice were fed AIN-93 M diets alone (control and Ang II groups) or supplemented with 10% w/w freeze-dried blackberry (BL + Ang II) or raspberry (RB + Ang II) powder for eight weeks. At week 4, mice were implanted with subcutaneous osmotic minipumps that delivered 0.9% saline (Control) or Ang II (1 µg/kg body weight/day) for another four weeks. BP was measured weekly by tail-cuff plethysmography and validated by direct measurement at endpoint using a BP catheter. Kidney expression of pro-oxidant enzymes such as NADPH oxidases (Nox) and antioxidant enzymes such as superoxide dismutates (SOD) were also measured. Results were analyzed using ANOVA followed by Tukey-Kramer post-hoc test. Results As expected, Ang II significantly increased systolic BP (SBP; 185 ± 4, n = 6, vs 132 ± 2 mmHg, n = 5, P < 0.001) and diastolic BP (124 ± 4, n = 6, vs 96 ± 2 mmHg, n = 4, P < 0.001) compared to control. Supplementation with BL and RB significantly attenuated this increase in SBP (143 ± 7 mmHg, n = 5, P < 0.0001 and 137 ± 4 mmHg, n = 5, P < 0.0001, respectively) and DBP (100 ± 6 mmHg, n = 5, P < 0.003 and 90 ± 3 mmHg, n = 5, P < 0.0001, respectively). Regarding the expression of NADPH oxidases in the kidney, Nox2 was significantly decreased by supplementation with BL (0.68 ± 0.07-fold, n = 5, P = 0.0005) and RB (0.70 ± 0.03-fold, n = 5, P = 0.0008) compared to Ang II (1.15 ± 0.12-fold, n = 5). Nox1 expression was up-regulated by Ang II compared to control (2.03 ± 0.16 vs 1.00 ± 0.00-fold, n = 5, P = 0.0001), but this was not prevented by supplementation with either berry. Nox4 expression was not affected by any of the treatments. Lastly, Ang II did not change the expression of SOD1 and SOD2 in the kidney, however, supplementation with RB significantly increased SOD1 (P = 0.02) and SOD2 (P = 0.005) expression compared to the other groups. Conclusions Our findings indicate that supplementation with BL and RB decrease BP in mice which may be related to a decrease in oxidative stress in the kidney. Studies are underway to further elucidate the mechanism by which BL and RB exert their antihypertensive effects. Funding Sources Arkansas Biosciences Institute and Lewis Foundation Grant Program.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 370-370
Author(s):  
Jasmynne Blacks ◽  
Rami Najjar ◽  
Christy Simecka ◽  
Shengyu Mu ◽  
Rafaela Feresin

Abstract Objectives To investigate whether diet supplementation with raspberry attenuate angiotensin (Ang) II- induced increase in oxidative stress, inflammation, and fibrosis in the heart of mice. Methods Twelve-week male C57BL/6J mice were fed AIN-93M diets alone (control and Ang II groups) or supplemented with 10% w/w freeze-dried raspberry (n = 5 per group). At week 4, mice were implanted with subcutaneous osmotic minipumps that delivered 0.9% saline (Control) or Ang II (1 µg/kg body weight/day) for another four weeks. Heart was collected at sacrifice and protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2), superoxide dismutase (SOD)2, and interleukin (IL)-6 were measured. Fibrosis was assessed using Masson's trichrome staining. Results were analyzed using ANOVA followed by Tukey-Kramer post-hoc test. Effect size (d) was also calculated to compare standardized changes among groups. Results Protein expression of Nrf2, a transcription factor that regulates the expression of antioxidant enzymes, was up-regulated by raspberry (1.57 ± 0.34 vs. 0.76 ± 0.15-fold, P = 0.09, d = 1.4) compared to Ang II, albeit not significantly. Ang II did not change the protein expression of the antioxidant enzyme SOD2 in the heart; however, supplementation with raspberry increased SOD2 (1.81 ± 0.33 vs. 1.09 ± 0.09-fold, P = 0.09; d = 1.1) expression compared to Ang II, though not significantly. Supplementation with raspberry significantly attenuated protein expression of the inflammatory cytokine IL-6 compared to Ang II (0.87 ± 0.19 vs. 1.4 ± 0.10-fold, P = 0.04, d = 1.8). Lastly, Ang II increased fibrosis in the heart of mice, which was attenuated by supplementation with raspberry. Conclusions Our findings indicate that raspberry may decrease Ang II-induced fibrosis by decreasing inflammation and oxidative stress in the heart. Funding Sources Arkansas Biosciences Institute & Lewis Foundation Grant Award.


2020 ◽  
Vol 70 (2) ◽  
pp. 227-237
Author(s):  
Eda Güneş

Abstract The aim of the this study was to evaluate the effects of fresh, dried and freeze-dried Centaurea depressa M. Bieb. (Asteraceae) on the oxidant and antioxidant status of the model organism D. melanogaster Meigen (Diptera: Drosophilidae) experimentally. The study was carried out from 2016 to 2019, and plant leaf extracts (0-50 mg/l) were added to insect standard artificial diets. The total protein, protein carbonyl content and glutathione-S-transferase, superoxide dismutase and catalase activities were quantified at the insect’s third larval stage. Our data showed that protein carbonyl content varied from 2.70 nmol/mg protein in the control group to 59.11 nmol/mg protein in the group fed with fresh leaf extract signifying induction of oxidative stress. All extracts increased the levels of all antioxidant enzymes and decreased the amounts of total protein. Meanwhile, the group fed with the freeze-dried extract showed no significant difference in the levels of total protein and protein carbonyl content except at the 50 mg/l concentration of the extract. Moreover, this group had superoxide dismutase and catalase activities 4 to 5 times higher than in the control group. In conclusion, induction of oxidative stress indicates that the fresh form of C. depressa leaves may have potential as a natural pesticide, whereas induction of endogenous antioxidant enzymes by the freeze-dried extract suggest its potential as an antioxidant.


2007 ◽  
Vol 292 (2) ◽  
pp. F861-F867 ◽  
Author(s):  
Melvin R. Hayden ◽  
Nazif A. Chowdhury ◽  
Shawna A. Cooper ◽  
Adam Whaley-Connell ◽  
Javad Habibi ◽  
...  

TG(mRen2)27 (Ren2) transgenic rats overexpress the mouse renin gene, with subsequent elevated tissue ANG II, hypertension, and nephropathy. The proximal tubule cell (PTC) is responsible for the reabsorption of 5–8 g of glomerular filtered albumin each day. Excess filtered albumin may contribute to PTC damage and tubulointerstitial disease. This investigation examined the role of ANG II-induced oxidative stress in PTC structural remodeling: whether such changes could be modified with in vivo treatment with ANG type 1 receptor (AT1R) blockade (valsartan) or SOD/catalase mimetic (tempol). Male Ren2 (6–7 wk old) and age-matched Sprague-Dawley rats were treated with valsartan (30 mg/kg), tempol (1 mmol/l), or placebo for 3 wk. Systolic blood pressure, albuminuria, N-acetyl-β-d-glucosaminidase, and kidney tissue malondialdehyde (MDA) were measured, and ×60,000 transmission electron microscopy images were used to assess PTC microvilli structure. There were significant differences in systolic blood pressure, albuminuria, lipid peroxidation (MDA and nitrotyrosine staining), and PTC structure in Ren2 vs. Sprague-Dawley rats (each P < 0.05). Increased mean diameter of PTC microvilli in the placebo-treated Ren2 rats ( P < 0.05) correlated strongly with albuminuria ( r2 = 0.83) and moderately with MDA ( r2 = 0.49), and there was an increase in the ratio of abnormal forms of microvilli in placebo-treated Ren2 rats compared with Sprague-Dawley control rats ( P < 0.05). AT1R blockade, but not tempol treatment, abrogated albuminuria and N-acetyl-β-d-glucosaminidase; both therapies corrected abnormalities in oxidative stress and PTC microvilli remodeling. These data indicate that PTC structural damage in the Ren2 rat is related to the oxidative stress response to ANG II and/or albuminuria.


2011 ◽  
Vol 301 (2) ◽  
pp. F364-F370 ◽  
Author(s):  
Anees Ahmad Banday ◽  
Mustafa F. Lokhandwala

Angiotensin (ANG) II via AT1 receptors (AT1Rs) maintains sodium homeostasis by regulating renal sodium transporters including Na+/H+ exchanger 3 (NHE3) in a biphasic manner. Low-ANG II concentration stimulates whereas high concentrations inhibit NHE3 activity. Oxidative stress has been shown to upregulate AT1R function that could modulate the ANG II-mediated NHE3 regulation. This study was designed to identify the signaling pathways responsible for ANG II-mediated biphasic regulation of proximal tubular NHE3 and the effect of oxidative stress on this phenomenon. Male Sprague-Dawley rats were chronically treated with a pro-oxidant l-buthionine sulfoximine (BSO) with and without an antioxidant tempol in tap water for 3 wk. BSO-treated rats exhibited oxidative stress and high blood pressure. At low concentration (1 pM) ANG II increased NHE3 activity in proximal tubules from all animals. However, in BSO-treated rats, the stimulation was more robust and was normalized by tempol treatment. ANG II (1 pM)-mediated NHE3 activation was abolished by AT1R blocker, intracellular Ca2+ chelator, and inhibitors of phospholipase C (PLC) and Ca2+-dependent calmodulin (CaM) but it was insensitive to Giα and protein kinase C inhibitors or AT2R antagonist. A high concentration of ANG II (1 μM) inhibited NHE3 activity in control and tempol-treated rats. However, in BSO-treated rats, ANG II (1 μM) continued to induce NHE3 stimulation. Tempol restored the inhibitory effect of ANG II (1 μM) in BSO-treated rats. The inhibitory effect of ANG II (1 μM) involved AT1R-dependent, cGMP-dependent protein kinase (PKG) activation and was independent of AT2 receptor and nitric oxide signaling. We conclude that ANG II stimulates NHE3 via AT1R-PLC-CaM pathway and inhibits NHE3 by AT1R-PKG activation. Oxidative stress impaired ANG II-mediated NHE3 biphasic response in that stimulation was observed at both high- and low-ANG II concentration.


Antioxidants ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 3 ◽  
Author(s):  
Bo Dam Lee ◽  
Jae-Myung Yoo ◽  
Seong Yeon Baek ◽  
Fu Yi Li ◽  
Dai-Eun Sok ◽  
...  

3,3′-Diindolylmethane (DIM), a metabolite of indole-3-carbinol present in Brassicaceae vegetables, possesses various health-promoting effects. Nonetheless, the effect of DIM on neurodegenerative diseases has not been elucidated clearly. In this study, we hypothesized DIM may protect neuronal cells against oxidative stress-induced apoptosis by promoting the formation of brain-derived neurotrophic factor (BDNF) and antioxidant enzymes through stabilizing the activation of the tropomyosin-related kinase receptor B (TrkB) cascade and we investigated the effect of DIM on oxidative stress-mediated neurodegenerative models. DIM protected neuronal cells against oxidative stress-induced apoptosis by regulating the expression of apoptosis-related proteins in glutamate-treated HT-22 cells. Additionally, DIM improved the expression of BDNF and antioxidant enzymes, such as heme oxygenase-1, glutamate-cysteine ligase catalytic subunit, and NAD(P)H quinine oxidoreductase-1, by promoting the activation of the TrkB/protein kinase B (Akt) pathway in the cells. Consistent with in vitro studies, DIM attenuated memory impairment by protecting hippocampal neuronal cells against oxidative damage in scopolamine-treated mice. Conclusionally, DIM exerted neuroprotective and antioxidant actions through the activation of both BDNF production and antioxidant enzyme formation in accordance with the TrkB/Akt pathway in neuronal cells. Such an effect of DIM may provide information for the application of DIM in the prevention of and therapy for neurodegenerative diseases.


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