scholarly journals Folic Acid Can Reduce Hyperhomocysteinemia-induced Vascular Damage by Immune/Inflammatory Response in Spontaneously Hypertensive Rats

2020 ◽  
Author(s):  
Lihua Zhang ◽  
Zhongliang li ◽  
Changcheng Xing ◽  
Ning Gao ◽  
Ping Cao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Folic Acid ◽  
Spontaneously Hypertensive Rats ◽  
Vascular Damage ◽  
Inflammatory Factors ◽  
Hypertensive Rats ◽  
Stress Indicators ◽  
Spontaneously Hypertensive ◽  
Inflammatory Molecules ◽  
Oxidative Stress Indicators

Abstract Background Hypertension associated with hyperhomocysteinemia (HHcy) is correlated with a high risk of vascular diseases. However, the mechanisms of HHcy-associated hypertensive vascular damage and the efficacy of folic acid (FA) as a treatment have not been fully elucidated. The aim of the present study was to evaluate the role of immune/inflammatory molecules and oxidizing factors in HHcy-associated hypertensive vascular damage, and to observe the intervention effect of FA on the two vascular injury factors. Methods Wistar-Kyoto rats (WKYs) and spontaneously hypertensive rats (SHRs) were administered DL-Hcy intraperitoneally to mimic HHcy and hypertension associated with HHcy for 12 weeks. WKYs and SHRs were randomized into WKY group, HHcy group, SHR group, SHR + HHcy group and SHR + HHcy + FA group. Mean tail artery blood pressure, plasma Hcy, serum SOD and MDA of rats in each group were compared. The thoracic aorta and bilateral carotid artery of rats were harvested for morphometric and immunostaining analyses. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect the expression of immune/inflammatory molecules such as TNF-α, IL-6, NF-κB p65/Rela and NF-κB2 and oxidative factors such as Nox2 and Nox4. Results We found that vascular inflammatory factors of vascular adhesion protein-1 (VAP-1), interleukin-6 (IL-6), and nuclear factor-κ-gene binding (NF-κB) p65/Rela in HHcy-associated hypertensive rats were significantly higher than those in SHRs (P༜0.05). While the oxidative stress indicators of Nox2 and Nox4 in HHcy-associated hypertensive rats were not significantly higher than those in SHRs (P༞0.05). Compared with SHRs, FA intervention in HHcy-associated hypertensive rats significantly increased serum superoxide dismutase (SOD) levels (P = 0.000) and significantly reduced vascular inflammatory factors of IL-6 and NF-κB p65/Rela (P༜0.05), but did not significantly change the oxidative stress indicators of Nox2 and Nox4 (P༞0.05). Conclusions HHcy-induced immune/inflammatory response plays a dominant role in vascular damage of HHcy-associated hypertensive rats. In addition to reducing the negative effects of HHcy, FA might involve unique antioxidant effects and inhibition of immune/inflammatory overreaction for HHcy-associated hypertensive rats.

The protective mechanism of folic acid on hyperhomocysteinemia-related arterial injury in spontaneously hypertensive rats: Folic acid against arterial inflammation

Vascular ◽  
2021 ◽  
pp. 170853812110365
Author(s):  
Lihua Zhang ◽  
Zhongliang Li ◽  
Changcheng Xing ◽  
Xiaoshan Ma ◽  
Rui Xu
Keyword(s):  
Oxidative Stress ◽  
Folic Acid ◽  
Spontaneously Hypertensive Rats ◽  
Arterial Injury ◽  
Rat Aorta ◽  
Control Group ◽  
Protective Mechanism ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Expression Levels

Background Hypertension associated with hyperhomocysteinemia (HHcy) is correlated with a high risk of vascular diseases. Studies found that folic acid (FA) supplementation can reduce the risk of cardiovascular and cerebrovascular events. The aim of the present study was to explore the potential mechanisms of FA attenuating HHcy-related arterial injury in spontaneously hypertensive rats (SHRs). Methods 24 SHRs were randomized into the control group, the HHcy group, and the HHcy + FA group (8 per group). The SHRs in the HHcy group and the HHcy + FA group were given DL-Hcy intraperitoneally to mimic hypertension associated with HHcy. The SHRs in the HHcy + FA group were given FA by gavage to mimic an FA-fortified diet. The histopathology and immunohistochemistry of rat aorta and carotid artery were analyzed, and the relative expression levels of immune/inflammation and oxidative stress molecules in arterial tissue were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Results FA significantly reduced the expression levels of nuclear factor-κ-gene binding (NF-κB) p65/Rela and interleukin-6 (IL-6) in rat arterial tissues, as well as the levels of plasma HHcy and serum malondialdehyde (MDA) in hypertension associated with HHcy rats ( p < 0.05). At the same time, FA significantly increased the serum superoxide dismutase (SOD) level in hypertension associated with HHcy rats, and even the SOD level of the HHcy + FA group was higher than that of the control group ( p < 0.05). However, HHcy induced the opposite results of the above indicators in SHRs compared with the control group ( p < 0.05). Conclusions The arterial protection mechanisms of FA are related to reducing the concentration of HHcy to eliminate the tissue toxicity of HHcy, inhibiting NF-κBp65/Rela/IL-6 pathway molecules to regulate inflammatory response, and promoting the potential anti-oxidative stress pathway molecules to reduce oxidative stress level.

In Vivo Evidence for Microvascular Oxidative Stress in Spontaneously Hypertensive Rats

Hypertension ◽  
1995 ◽  
Vol 25 (5) ◽  
pp. 1083-1089 ◽  
Author(s):  
Hidekazu Suzuki ◽  
Allen Swei ◽  
Benjamin W. Zweifach ◽  
Geert W. Schmid-Schönbein
Keyword(s):  
Oxidative Stress ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

scholarly journals Immunohistochemical Analysis of 4-HNE, NGAL, and HO-1 Tissue Expression after Apocynin Treatment and HBO Preconditioning in Postischemic Acute Kidney Injury Induced in Spontaneously Hypertensive Rats

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1163
Author(s):  
Sanjin Kovacevic ◽  
Milan Ivanov ◽  
Maja Zivotic ◽  
Predrag Brkic ◽  
Zoran Miloradovic ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Spontaneously Hypertensive Rats ◽  
Kidney Injury ◽  
Immunohistochemical Analysis ◽  
Tissue Expression ◽  
Pure Oxygen ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Renal Expression

Oxidative stress has been considered as a central aggravating factor in the development of postischemic acute kidney injury (AKI). The aim of this study was to perform the immunohistochemical analysis of 4-hydroxynonenal (4-HNE), neutrophil gelatinase-associated lipocalin (NGAL), and heme oxygenase-1 (HO-1) tissue expression after apocynin (APO) treatment and hyperbaric oxygenation (HBO) preconditioning, applied as single or combined protocol, in postischemic acute kidney injury induced in spontaneously hypertensive rats (SHR). Twenty-four hours before AKI induction, HBO preconditioning was carried out by exposing to pure oxygen (2.026 bar) twice a day, for 60 min in two consecutive days. Acute kidney injury was induced by removal of the right kidney while the left renal artery was occluded for 45 min by atraumatic clamp. Apocynin was applied in a dose of 40 mg/kg body weight, intravenously, 5 min before reperfusion. We showed increased 4-HNE renal expression in postischemic AKI compared to Sham-operated (SHAM) group. Apocynin treatment, with or without HBO preconditioning, improved creatinine and phosphate clearances, in postischemic AKI. This improvement in renal function was accompanied with decreased 4-HNE, while HO-1 kidney expression restored close to the control group level. NGAL renal expression was also decreased after apocynin treatment, and HBO preconditioning, with or without APO treatment. Considering our results, we can say that 4-HNE tissue expression can be used as a marker of oxidative stress in postischemic AKI. On the other hand, apocynin treatment and HBO preconditioning reduced oxidative damage, and this protective effect might be expected even in experimental hypertensive condition.

scholarly journals Diabetes mellitus activates fetal gene program and intensifies cardiac remodeling and oxidative stress in aged spontaneously hypertensive rats

2013 ◽  
Vol 12 (1) ◽  
pp. 152 ◽  
Author(s):  
Camila Rosa ◽  
Natasha Xavier ◽  
Dijon Henrique Campos ◽  
Ana Angélica Fernandes ◽  
Marcelo Diarcadia Cezar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Cardiac Remodeling ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
And Oxidative Stress

scholarly journals Oxidative stress induces BH4 deficiency in male, but not female, SHR

2018 ◽  
Vol 38 (4) ◽  
Author(s):  
Ellen E. Gillis ◽  
Krystal N. Brinson ◽  
Olga Rafikova ◽  
Wei Chen ◽  
Jacqueline B. Musall ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Spontaneously Hypertensive Rats ◽  
No Synthase ◽  
Hypertensive Rats ◽  
Male And Female ◽  
Spontaneously Hypertensive ◽  
No Bioavailability ◽  
Renal Inner Medulla ◽  
Relative Deficiency ◽  
To Receive

We previously published that female spontaneously hypertensive rats (SHR) have significantly greater nitric oxide (NO) bioavailability and NO synthase (NOS) enzymatic activity in the renal inner medulla (IM) compared with age-matched males, although the mechanism responsible remains unknown. Tetrahydrobiopterin (BH4) is a critical cofactor required for NO generation, and decreases in BH4 as a result of increases in oxidative stress have been implicated in the pathogenesis of hypertension. As male SHR are known to have higher levels of oxidative stress compared with female SHR, we hypothesized that relative BH4 deficiency induced by oxidative stress in male SHR results in lower levels of NOS activity in renal IM compared with females. Twelve-week-old male and female SHR were randomized to receive tempol (30 mg/kg/day via drinking water) or vehicle for 2 weeks. Tempol treatment did not affect blood pressure (BP) in either sex, but reduced peroxynitrite levels only in males. Females had more total biopterin, dihydrobiopterin (BH2), and BH4 levels in renal IMs than males, and tempol treatment eliminated these sex differences. Females had greater total NOS activity in the renal IM than males, and adding exogenous BH4 to the assay increased NOS activity in both sexes. This sex difference in total NOS and the effect of exogenous BH4 were abolished with tempol treatment. We conclude that higher oxidative stress in male SHR results in a relative deficiency of BH4 compared with females, resulting in diminished renal NOS activity in the male.

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