İlhan İlter, Asci Halil, Ozmen Ozlem, Buyukbayram Halil İbrahim, Arlıoglu Melih, Kurtbolat Okan
Department of Biochemistry, Faculty of Medicine, Suleyman Demirel University, Isparta, 32200, Turkey.
Department of Pharmacology, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Feb;398(2):1841-1851. doi: 10.1007/s00210-024-03391-2. Epub 2024 Aug 24.
Sepsis-induced renal damage poses a significant threat, necessitating effective therapeutic strategies. Cannabidiol (CBD) has beneficial effects on tissues and their functions by exhibiting antioxidant and anti-inflammatory effects. This study investigates the potential protective effects of CBD in mitigating lipopolysaccharide (LPS)-induced renal injury in Wistar Albino rats. Thirty-two Wistar Albino rats were categorized into control, LPS (5 mg/kg i.p.), LPS + CBD, and CBD (5 mg/kg i.p.) groups. After the experiment, samples were collected for biochemical, genetic, histopathological, and immunohistochemical analyses. Oxidative stress markers as total oxidant status (TOS) and total antioxidant status (TAS), oxidative stress index (OSI), superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA), immune staining as tumor necrosis factor alpha (TNF-α), interleukin-10 (IL-10), caspase-3, gene expressions as nuclear factor erythroid 2-related factor 2 (NRF2), C/EBP homologous protein (CHOP), caspase-9, glucose-regulating protein 78 (GRP78), B-cell leukemia/lymphoma 2 (Bcl2), and tissue histology have been examined. The LPS-exposed group exhibited significant renal abnormalities, mitigated by CBD intervention in the LPS + CBD group. CBD reduced immunoexpression scores for TNF-α, caspase-3, and IL-10. Biochemically, CBD induced a positive shift in the oxidative balance, increasing TAS, SOD, and GPx, while decreasing TOS, OSI, and MDA levels. Genetic analyses highlighted CBD's regulatory impact on NRF2, CHOP, caspase-9, GRP78, and Bcl2, providing molecular insights into its protective role against LPS-induced renal damage. This study underscores CBD as a promising protective agent against sepsis-induced renal damage. Our findings could provide valuable insights into potential therapeutic avenues for addressing renal complications in sepsis.
脓毒症诱导的肾损伤构成重大威胁，因此需要有效的治疗策略。大麻二酚（CBD）通过展现抗氧化和抗炎作用，对组织及其功能具有有益影响。本研究调查了CBD在减轻脂多糖（LPS）诱导的Wistar白化大鼠肾损伤方面的潜在保护作用。32只Wistar白化大鼠被分为对照组、LPS组（5mg/kg腹腔注射）、LPS + CBD组和CBD组（5mg/kg腹腔注射）。实验结束后，收集样本进行生化、基因、组织病理学和免疫组织化学分析。检测了氧化应激标志物如总氧化剂状态（TOS）和总抗氧化剂状态（TAS）、氧化应激指数（OSI）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GPx）、丙二醛（MDA），免疫染色如肿瘤坏死因子α（TNF-α）、白细胞介素-10（IL-10）、半胱天冬酶-3，基因表达如核因子红细胞2相关因子2（NRF2）、C/EBP同源蛋白（CHOP）、半胱天冬酶-9、葡萄糖调节蛋白78（GRP78）、B细胞白血病/淋巴瘤2（Bcl2），并进行了组织组织学检查。LPS暴露组表现出明显的肾脏异常，而在LPS + CBD组中，CBD干预减轻了这些异常。CBD降低了TNF-α、半胱天冬酶-3和IL-10的免疫表达评分。在生化方面，CBD使氧化平衡发生正向变化，增加了TAS、SOD和GPx，同时降低了TOS、OSI和MDA水平。基因分析突出了CBD对NRF2、CHOP、半胱天冬酶-9、GRP78和Bcl2的调节作用，为其对LPS诱导的肾损伤的保护作用提供了分子层面的见解。本研究强调CBD是一种有前景的抗脓毒症诱导肾损伤的保护剂。我们的研究结果可为解决脓毒症肾并发症的潜在治疗途径提供有价值的见解。
