Sarawi Wedad S, Alhusaini Ahlam M, Fadda Laila M, Alomar Hatun A, Albaker Awatif B, Aljrboa Amjad S, Alotaibi Areej M, Hasan Iman H, Mahmoud Ayman M
Pharmacology and Toxicology Department, Faculty of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Department of Pharmacology and Toxicology, College of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia.
Molecules. 2021 Sep 15;26(18):5591. doi: 10.3390/molecules26185591.
Copper (Cu) is essential for multiple biochemical processes, and copper sulphate (CuSO) is a pesticide used for repelling pests. Accidental or intentional intoxication can induce multiorgan toxicity and could be fatal. Curcumin (CUR) is a potent antioxidant, but its poor systemic bioavailability is the main drawback in its therapeutic uses. This study investigated the protective effect of CUR and N-CUR on CuSO-induced cerebral oxidative stress, inflammation, and apoptosis in rats, pointing to the possible involvement of Akt/GSK-3β. Rats received 100 mg/kg CuSO and were concurrently treated with CUR or N-CUR for 7 days. Cu-administered rats exhibited a remarkable increase in cerebral malondialdehyde (MDA), NF-κB p65, TNF-α, and IL-6 associated with decreased GSH, SOD, and catalase. Cu provoked DNA fragmentation, upregulated BAX, caspase-3, and p53, and decreased BCL-2 in the brain of rats. N-CUR and CUR ameliorated MDA, NF-κB p65, and pro-inflammatory cytokines, downregulated pro-apoptotic genes, upregulated BCL-2, and enhanced antioxidants and DNA integrity. In addition, both N-CUR and CUR increased AKT Ser473 and GSK-3β Ser9 phosphorylation in the brain of Cu-administered rats. In conclusion, N-CUR and CUR prevent Cu neurotoxicity by attenuating oxidative injury, inflammatory response, and apoptosis and upregulating AKT/GSK-3β signaling. The neuroprotective effect of N-CUR was more potent than CUR.
铜（Cu）对多种生化过程至关重要，而硫酸铜（CuSO）是一种用于驱虫的杀虫剂。意外或故意中毒可导致多器官毒性，甚至可能致命。姜黄素（CUR）是一种有效的抗氧化剂，但其较差的全身生物利用度是其治疗应用中的主要缺点。本研究调查了CUR和N - CUR对硫酸铜诱导的大鼠脑氧化应激、炎症和细胞凋亡的保护作用，指出Akt/GSK - 3β可能参与其中。大鼠接受100 mg/kg硫酸铜，并同时用CUR或N - CUR治疗7天。给予铜的大鼠脑内丙二醛（MDA）、NF - κB p65、肿瘤坏死因子 - α（TNF - α）和白细胞介素 - 6（IL - 6）显著增加，同时谷胱甘肽（GSH）、超氧化物歧化酶（SOD）和过氧化氢酶减少。铜引发大鼠脑内DNA片段化，上调BAX、半胱天冬酶 - 3（caspase - 3）和p53，并降低BCL - 2。N - CUR和CUR改善了MDA、NF - κB p65和促炎细胞因子，下调促凋亡基因，上调BCL - 2，并增强抗氧化剂和DNA完整性。此外，N - CUR和CUR均增加了给予铜的大鼠脑内AKT Ser473和GSK - 3β Ser9的磷酸化。总之，N - CUR和CUR通过减轻氧化损伤、炎症反应和细胞凋亡以及上调AKT/GSK - 3β信号传导来预防铜神经毒性。N - CUR的神经保护作用比CUR更强。
