Wali Adil Farooq, Rehman Muneeb U, Raish Mohammad, Kazi Mohsin, Rao Padma G M, Alnemer Osamah, Ahmad Parvaiz, Ahmad Ajaz
Department of Pharmaceutical Chemistry, RAK College of Pharmaceutical Sciences, RAK Medical and Health Science University, Ras Al Khaimah 11171, UAE.
Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Molecules. 2020 Nov 4;25(21):5127. doi: 10.3390/molecules25215127.
The present investigation aimed to evaluate the protective effect of Zingerone (ZIN) against lipopolysaccharide-induced oxidative stress, DNA damage, and cytokine storm in rats. For survival study the rats were divided into four groups (n = 10). The control group was treated with normal saline; Group II received an intraperitoneal (i.p) injection (10 mg/kg) of LPS as disease control. Rats in Group III were treated with ZIN 150 mg/kg (p.o) 2 h before LPS challenge and rats in Group IV were given ZIN only. Survival of the rats was monitored up to 96 h post LPS treatment. In another set, the animals were divided into four groups of six rats. Animals in Group I served as normal control and were treated with normal saline. Animals in Group II were treated with lipopolysaccharide (LPS) and served as disease control. Group III animals were treated with ZIN 2 h before LPS challenge. Group IV served as positive control and were treated with ZIN (150 mg/kg orally). The blood samples were collected and used for the analysis of biochemical parameters like alanine transaminase (ALT), alkaline phosphatase (ALP), aspartate transaminase (AST), blood urea nitrogen (BUN), Cr, Urea, lactate dehydrogenase (LDH), albumin, bilirubin (BIL), and total protein. Oxidative stress markers malondialdehyde (MDA), glutathione peroxidase (GSH), myeloperoxidase (MPO), and (DNA damage marker) 8-OHdG levels were measured in different organs. Level of nitric oxide (NO) and inflammatory markers like TNF-α, IL-1ß, IL-1α, IL-2, IL-6, and IL-10 were also quantified in plasma. Procalcitonin (PCT), a sepsis biomarker, was also measured. ZIN treatment had shown significant ( < 0.5) restoration of plasma enzymes, antioxidant markers and attenuated plasma proinflammatory cytokines and sepsis biomarker (PCT), thereby preventing the multi-organ and tissue damage in LPS-induced rats also confirmed by histopathological studies of different organs. The protective effect of ZIN may be due to its potent antioxidant potential. Thus ZIN can prevent LPS-induced oxidative stress as well as inflammatory and multi-organ damage in rats when administered to the LPS treated animals.
本研究旨在评估姜辣素（ZIN）对脂多糖诱导的大鼠氧化应激、DNA损伤和细胞因子风暴的保护作用。在生存研究中，将大鼠分为四组（n = 10）。对照组用生理盐水处理；第二组腹腔注射（i.p）10 mg/kg脂多糖作为疾病对照。第三组大鼠在脂多糖攻击前2小时口服150 mg/kg ZIN，第四组只给予ZIN。在脂多糖处理后96小时内监测大鼠的存活情况。在另一组实验中，将动物分为四组，每组六只。第一组动物作为正常对照，用生理盐水处理。第二组动物用脂多糖（LPS）处理作为疾病对照。第三组动物在脂多糖攻击前2小时用ZIN处理。第四组作为阳性对照，口服ZIN（150 mg/kg）。采集血样用于分析生化参数，如丙氨酸转氨酶（ALT）、碱性磷酸酶（ALP）、天冬氨酸转氨酶（AST）、血尿素氮（BUN）、肌酐、尿素、乳酸脱氢酶（LDH）、白蛋白、胆红素（BIL）和总蛋白。测量不同器官中的氧化应激标志物丙二醛（MDA）、谷胱甘肽过氧化物酶（GSH）、髓过氧化物酶（MPO）以及（DNA损伤标志物）8-羟基脱氧鸟苷（8-OHdG）水平。还对血浆中的一氧化氮（NO）水平以及肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1ß）、白细胞介素-1α（IL-1α）、白细胞介素-2（IL-2）、白细胞介素-6（IL-6）和白细胞介素-10（IL-10）等炎症标志物进行定量分析。还测量了脓毒症生物标志物降钙素原（PCT）。ZIN治疗显著（P < 0.5）恢复了血浆酶、抗氧化标志物水平，并减轻了血浆促炎细胞因子和脓毒症生物标志物（PCT）的水平，从而预防了脂多糖诱导的大鼠多器官和组织损伤，不同器官的组织病理学研究也证实了这一点。ZIN的保护作用可能归因于其强大的抗氧化潜力。因此，当给脂多糖处理的动物施用ZIN时，它可以预防脂多糖诱导的大鼠氧化应激以及炎症和多器官损伤。
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