Faculty of Applied Medical Sciences, Department of Laboratory Medicine, Umm Al-Qura University, Makkah, Saudi Arabia.
Faculty of Veterinary Medicine, Department of Clinical Pathology, Mansoura University, Mansoura, Egypt.
J Biochem Mol Toxicol. 2020 Mar;34(3):e22440. doi: 10.1002/jbt.22440. Epub 2020 Jan 11.
Although vitamin D (VD) and calcium (Ca) attenuate cadmium (Cd) metabolism, their combined antioxidant and anti-inflammatory actions against Cd toxicity have not been previously explored. Hence, this study measured the protective effects of VD ± Ca supplements against Cd hepatotoxicity. Forty adult male rats were distributed to: negative controls (NCs), positive controls (PCs), VD, Ca, and VD and Ca (VDC) groups. All groups, except NC, received CdCl in drinking water (44 mg/L) for 4 weeks individually or concurrently with intramuscular VD (600 IU/kg; three times per week) and/or oral Ca (100 mg/kg; five times per week). The PC group showed abnormal hepatic biochemical parameters and increase in cellular cytochrome C, caspase-9, and caspase-3 alongside the apoptotic/necrotic cell numbers by terminal deoxynucleotidyl transferase dUTP nick end labeling technique. The PC hepatic tissue also had substantially elevated pro-oxidants (malondialdehyde [MDA]/H O /protein carbonyls) and inflammatory cytokines (interleukin 1β [IL-1β]/IL-6/IL17A/tumor necrosis factor-α), whereas the anti-inflammatory (IL-10/IL-22) and antioxidants (glutathione [GSH]/GPx/catalase enzyme [CAT]) markers declined. Hypovitaminosis D, low hepatic tissue Ca, aberrant hepatic expression of VD-metabolizing enzymes (Cyp2R1/Cyp27a1/cyp24a1), receptor and binding protein alongside Ca-membrane (Ca 1.1/Ca 3.1), and store-operated (RyR1/ITPR1) channels, and Ca-binding proteins (CAM/CAMKIIA/S100A1/S100B) were observed in the PC group. Both monotherapies decreased serum, but not tissue Cd levels, restored the targeted hepatic VD/Ca molecules' expression. However, these effects were more prominent in the VD group than the Ca group. The VDC group, contrariwise, disclosed the greatest alleviations on serum and tissue Cd, inflammatory and oxidative markers, the VD/Ca molecules and tissue integrity. In conclusion, this report is the first to reveal boosted protection for cosupplementing VD and Ca against Cd hepatotoxicity that could be due to enhanced antioxidative, anti-inflammatory, and modulation of the Ca pathways.
尽管维生素 D (VD) 和钙 (Ca) 可以减轻镉 (Cd) 的代谢，但它们联合的抗氧化和抗炎作用对抗 Cd 毒性尚未被探索。因此，本研究测量了 VD ± Ca 补充剂对 Cd 肝毒性的保护作用。40 只成年雄性大鼠被分为：阴性对照组 (NCs)、阳性对照组 (PCs)、VD 组、Ca 组和 VD 和 Ca (VDC) 组。除 NC 组外，所有组均单独或同时给予 CdCl 饮用水 (44mg/L)4 周，或肌肉内给予 VD (600IU/kg；每周 3 次) 和/或口服 Ca (100mg/kg；每周 5 次)。PC 组表现出异常的肝生化参数和细胞色素 C、半胱天冬氨酸蛋白酶-9 和半胱天冬氨酸蛋白酶-3 的增加，以及末端脱氧核苷酸转移酶 dUTP 缺口末端标记技术的凋亡/坏死细胞数量的增加。PC 肝组织还具有显著升高的促氧化剂 (丙二醛 [MDA]/H O /蛋白质羰基) 和炎性细胞因子 (白细胞介素 1β [IL-1β]/IL-6/IL17A/肿瘤坏死因子-α)，而抗炎 (IL-10/IL-22) 和抗氧化剂 (谷胱甘肽 [GSH]/GPx/过氧化氢酶 [CAT]) 标志物下降。维生素 D 缺乏症、肝组织 Ca 含量低、VD 代谢酶 (Cyp2R1/Cyp27a1/cyp24a1)、受体和结合蛋白以及 Ca 膜 (Ca 1.1/Ca 3.1) 和储存操作 (RyR1/ITPR1) 通道的异常表达以及 Ca 结合蛋白 (CAM/CAMKIIA/S100A1/S100B) 在 PC 组中观察到。两种单一疗法均降低了血清而非组织 Cd 水平，恢复了靶向肝 VD/Ca 分子的表达。然而，VD 组的这些作用比 Ca 组更为明显。相反，VDC 组在血清和组织 Cd、炎症和氧化标志物、VD/Ca 分子和组织完整性方面显示出最大的缓解。总之，本报告首次揭示了 VD 和 Ca 联合补充对 Cd 肝毒性的增强保护作用，这可能是由于增强的抗氧化、抗炎和 Ca 途径的调节。
