Department of Pharmacology and therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, 17666 Al Ain, UAE.
Department of Pharmaceutical Biosciences, Biomedical Centre, Uppsala University, 591751 24 Uppsala, Sweden.
Molecules. 2020 Sep 30;25(19):4492. doi: 10.3390/molecules25194492.
Physiological Glucocorticoids are important regulators of the immune system. Pharmacological GCs are in widespread use to treat inflammatory diseases. Adrenalectomy (ADX) has been shown to exacerbate renal injury through inflammation and oxidative stress that results in renal impairment due to depletion of GCs. In this study, the effect of myrcene to attenuate renal inflammation and oxidative stress was evaluated in the adrenalectomized rat model. Rats were adrenalectomized bilaterally or the adrenals were not removed after surgery (sham). Myrcene (50 mg/kg body weight, orally) was administered post ADX. Myrcene treatment resulted in significant downregulation of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) compared to untreated ADX rats. In addition, myrcene resulted in significant downregulation of immunomodulatory factors (IFNγ and NF-κB) and anti-inflammatory markers (IL-4 and IL-10) in treated ADX compared to untreated ADX. Myrcene significantly increased the antioxidant molecules (CAT, GSH, and SOD) and decreased MDA levels in treated ADX compared to untreated. Moreover, myrcene treatment reduced the expression of COX-2, iNOS, KIM-1, and kidney functional molecules (UREA, LDH, total protein, and creatinine) in ADX treated compared to ADX untreated. These results suggest that myrcene could be further developed as a therapeutic drug for treatment of kidney inflammation and injury.
生理糖皮质激素是免疫系统的重要调节剂。药理学糖皮质激素被广泛用于治疗炎症性疾病。肾上腺切除术(ADX)已被证明通过炎症和氧化应激加重肾脏损伤,导致糖皮质激素耗竭引起的肾功能损害。在这项研究中,评估了桃金娘烯醇在去肾上腺大鼠模型中减轻肾脏炎症和氧化应激的作用。大鼠双侧行肾上腺切除术或手术后不切除肾上腺(假手术)。ADX 后给予桃金娘烯醇(50mg/kg 体重,口服)。与未治疗的 ADX 大鼠相比,桃金娘烯醇治疗导致促炎细胞因子(IL-1β、IL-6 和 TNF-α)显著下调。此外,与未治疗的 ADX 相比,桃金娘烯醇治疗在 ADX 中导致免疫调节因子(IFNγ和 NF-κB)和抗炎标志物(IL-4 和 IL-10)的显著下调。与未治疗的 ADX 相比,桃金娘烯醇在 ADX 中显著增加抗氧化分子(CAT、GSH 和 SOD)并降低 MDA 水平。此外,与 ADX 未治疗相比,桃金娘烯醇治疗降低了 COX-2、iNOS、KIM-1 和肾脏功能分子(UREA、LDH、总蛋白和肌酐)的表达。这些结果表明,桃金娘烯醇可以进一步开发为治疗肾脏炎症和损伤的治疗药物。