Yousefzadeh Nasibeh, Jeddi Sajad, Kashfi Khosrow, Ghasemi Asghar
Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Molecular, Cellular, and Biomedical Sciences, Sophie Davis School of Biomedical Education, City University of New York School of Medicine, NY, USA.
EXCLI J. 2022 Aug 24;21:1151-1166. doi: 10.17179/excli2022-5082. eCollection 2022.
The risk of osteoporotic fractures increases in women after menopause. This study aims at determining the effects of long-term inorganic nitrate administration against ovariectomy-induced osteoporosis in rats. Rats were divided into 4 groups (n=6/group): Control, control+nitrate, ovariectomized (OVX), and OVX+nitrate. Sodium nitrate (100 mg/L in drinking water) was administered for 9 months. Trabecular bone quality in the proximal tibia was measured using a Micro-Computed Tomography (micro-CT) scanner at months 0, 1, 3, and 9. Levels of nitric oxide (NO) metabolites (NOx) and oxidative stress indices, and mRNA expression of endothelial NO synthase (eNOS) were measured at month 9 in the proximal tibia. Compared to controls, OVX rats had lower NOx levels by 47 %, eNOS mRNA expression by 55 %, catalase activity (CAT) by 45 %, total antioxidant capacity (TAC) by 70 %, and higher malondialdehyde (MDA) levels by 327 % in the bone tissue at month 9. OVX rats, compared to controls, had lower bone volume/tissue volume (BV/TV), trabecular number (Tb.N.), and trabecular thickness (Tb.Th.) by 32 %, 58 %, and 17 %, respectively, and higher trabecular separation (Tb.Sp.) by 123 %, at month 9. Nitrate administration to control rats increased TAC by 46 % in the bone tissue at month 9 but did not significantly affect other parameters in serum and bone tissue. Nitrate in OVX rats significantly increased NOx levels by 86 %, eNOS expression by 2.14-fold, CAT activity by 75 %, TAC by 170 %, and decreased MDA levels by 36 % at month 9 in the bone tissue. Nitrate-treated OVX rats at month 9 had higher BV/TV (42 %) and Tb.N. (61 %) and lower Tb.Sp. (15 %). Long-term inorganic nitrate administration at a low dose has protective effects against OVX-induced osteoporosis in rats; this effect is associated with increasing eNOS-derived NO and decreasing oxidative stress in the bone tissue.
绝经后女性骨质疏松性骨折的风险会增加。本研究旨在确定长期给予无机硝酸盐对去卵巢诱导的大鼠骨质疏松症的影响。将大鼠分为4组（每组n = 6）：对照组、对照+硝酸盐组、去卵巢（OVX）组和OVX+硝酸盐组。给予硝酸钠（饮用水中100 mg/L）9个月。在第0、1、3和9个月时，使用微型计算机断层扫描（micro-CT）扫描仪测量胫骨近端的小梁骨质量。在第9个月时，测量胫骨近端一氧化氮（NO）代谢物（NOx）水平、氧化应激指标以及内皮型一氧化氮合酶（eNOS）的mRNA表达。与对照组相比，在第9个月时，OVX大鼠骨组织中的NOx水平降低了47%，eNOS mRNA表达降低了55%，过氧化氢酶活性（CAT）降低了45%，总抗氧化能力（TAC）降低了70%，而丙二醛（MDA）水平升高了327%。与对照组相比，在第9个月时，OVX大鼠的骨体积/组织体积（BV/TV）、小梁数量（Tb.N.）和小梁厚度（Tb.Th.）分别降低了32%、58%和17%，而小梁间距（Tb.Sp.）升高了123%。在第9个月时，给予对照组大鼠硝酸盐使骨组织中的TAC增加了46%，但对血清和骨组织中的其他参数没有显著影响。在第9个月时，OVX大鼠中的硝酸盐使骨组织中的NOx水平显著升高了86%，eNOS表达增加了2.14倍，CAT活性增加了75%，TAC增加了170%，MDA水平降低了36%。在第9个月时，经硝酸盐处理的OVX大鼠的BV/TV（42%）和Tb.N.（61%）更高，Tb.Sp.（15%）更低。长期低剂量给予无机硝酸盐对去卵巢诱导的大鼠骨质疏松症具有保护作用；这种作用与增加骨组织中eNOS衍生的NO并降低氧化应激有关。
