Protective effects of long-term nitrate administration against ovariectomy-induced kidney dysfunction in rats

Yousefzadeh, Nasibeh; Jeddi, Sajad; Zarkesh, Maryam; Norouzirad, Reza; Kashfi, Khosrow; Ghasemi, Asghar

doi:10.1007/s43440-023-00499-9

Pharmacol. Rep

2023

DOI: 10.1007/s43440-023-00499-9

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Protective effects of long-term nitrate administration against ovariectomy-induced kidney dysfunction in rats

Nasibeh Yousefzadeh

Sajad Jeddi

Maryam Zarkesh

et al.

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2024

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Cited by 2 publications

References 87 publications

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Chronic Inorganic Nitrate Administration Increases the Expression of Genes Involved in the Browning of Gonadal Adipose Tissue in Ovariectomized Rats

Yousefzadeh,

Jeddi,

Ghasemi

2024

EMIDDT

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Background and Objective:: Nitrate, as nitric oxide (NO) donor, has been suggested as a nutrition-based treatment for decreasing the risk of menopause-related obesity. This study aimed to specify the effects of chronic inorganic nitrate administration on uncoupling protein-1 (UCP-1), peroxisome proliferator-activated-receptor-γ (PPAR-γ) coactivator-1α (PGC-1α), and PPAR-γ expression in gonadal adipose tissue (GAT) of ovariectomized (OVX) rats. Methods:: Female rats were assigned to 3 groups: Control, OVX, and OVX+nitrate (n=7/group), which consumed water containing inorganic nitrate (100 mg/L) for 9 months. At month 9, GAT was used for the measurement of NO metabolites (NOx), mRNA levels of NO synthases [endothelial (eNOS), inducible (iNOS), neuronal (nNOS)], and mRNA and protein levels of UCP-1, PGC-1α, and PPAR-γ. Conclusion:: In OVX rats, chronic nitrate administration increased gene and protein levels of UCP-1, PGC-1α, and PPAR-γ in GAT, indicating the anti-obesity effects of nitrate are partially mediated by the white adipose tissue (WAT) browning. Moreover, the stimulatory effect of inorganic nitrate on the WAT browning in OVX rats was associated with blunting the OVXinduced NO deficiency in GAT. result: OVX rats had lower NOx concentration (45%) and eNOS (38%) and nNOS (30%) expression in GAT that was restored to normal values following nitrate administration. OVX rats had significantly lower mRNA and protein levels of UCP-1 (83% and 30%), PGC-1α (65% and 39%), and PPAR-γ (66% and 34.5%) in OAT. Chronic inorganic nitrate administration in OVX-rats increased mRNA (236%, 115%, and 128%) and protein (38%, 43%, and 34%, respectively) levels of PPAR-γ, PGC-1α, and UCP-1, respectively.

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Chronic Inorganic Nitrate Administration Increases the Expression of Genes Involved in the Browning of Gonadal Adipose Tissue in Ovariectomized Rats

Yousefzadeh,

Jeddi,

Ghasemi

2024

EMIDDT

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Preventive Effects of Resistance Training on Hemodynamics and Kidney Mitochondrial Bioenergetic Function in Ovariectomized Rats

Queiroz,

Garcia,

Silva

et al. 2024

IJMS

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Menopause occurs due to the depletion of the ovarian reserve, leading to a progressive decline in estrogen (E2) levels. This decrease in E2 levels increases the risk of developing several diseases and can coexist with chronic kidney disease (CKD). Arterial hypertension (AH) is another condition associated with menopause and may either contribute to or result from CKD. Ovariectomy (OVX) induces hypoestrogenism, which can lead to mitochondrial bioenergetic dysfunction in the kidneys. Previous studies have suggested that exercise training has beneficial effects on adults with CKD and AH. To investigate the effects of OVX and resistance training (RT) on hemodynamic parameters and mitochondrial bioenergetic function of the kidney, female Wistar rats were divided into ovariectomized (OVX) and intact (INT) groups. These rats were either kept sedentary (SED) or subjected to RT for thirteen weeks. The RT involved climbing a vertical ladder with a workload apparatus. Hemodynamic parameters were assessed via tail plethysmography. Mitochondrial respiratory function was evaluated with high-resolution respirometry. Gene expression related to the electron transport chain (ETC) and oxidative phosphorylation (OXPHOS) was evaluated by real-time qPCR. At week 13, key hemodynamic parameters (systolic blood pressure and mean arterial pressure) were significantly elevated in the OVX-SED group. Compared with those in the other groups, mitochondrial bioenergetics were impaired in the OVX-SED group. In contrast, the trained groups presented improved mitochondrial bioenergetic function compared with the sedentary groups. OVX led to reduced gene expression related to the mitochondrial ETC and OXPHOS, whereas RT both prevented this reduction and increased gene expression in the trained groups. Our results indicate that hypoestrogenism significantly decreases OXPHOS and ETC capacity in the kidneys of sedentary animals. However, RT effectively increased the expression of genes related to mitochondrial ETC and OXPHOS, thereby counteracting the effects of OVX.

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Protective effects of long-term nitrate administration against ovariectomy-induced kidney dysfunction in rats

Cited by 2 publications

References 87 publications

Chronic Inorganic Nitrate Administration Increases the Expression of Genes Involved in the Browning of Gonadal Adipose Tissue in Ovariectomized Rats

Chronic Inorganic Nitrate Administration Increases the Expression of Genes Involved in the Browning of Gonadal Adipose Tissue in Ovariectomized Rats

Preventive Effects of Resistance Training on Hemodynamics and Kidney Mitochondrial Bioenergetic Function in Ovariectomized Rats

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