Hama Said Hogr Jasim, Ahmed Zheen Aorahman
Department of Pharmacology and Toxicology, College of Pharmacy, University of Sulaimani, Sulaimani, Kurdistan Region, Iraq.
Biologics. 2025 Jul 3;19:399-412. doi: 10.2147/BTT.S523547. eCollection 2025.
The present study was designed to determine the anti-inflammatory and antioxidant effects of dulaglutide (DUL) on doxorubicin (DOX) -induced acute kidney injury (AKI).
Twenty-eight male rats were randomly allocated into four groups: the negative control group (received Distilled water), the positive control group (received Distilled water and a single dose of DOX), DUL 0.2 mg/kg group (received DUL 0.2 mg/kg twice weekly and single dose of DOX), and DUL 0.6 mg/kg group (received DUL 0.2 mg/kg twice weekly and single dose of DOX). All DOX doses (20 mg/kg) were given at day 13th of the study and all treatments were administered intraperitoneally for 14 days. On day fifteenth, the rats were sacrificed, and blood was collected to measure the complete blood count (CBC), Neutrophile/Lymphocyte Ratio (NLR), Monocyte/Lymphocyte Ratio (MLR), And Platelet/Lymphocyte Ratio (PLR), C-reactive protein (CRP), blood urea nitrogen (BUN), and serum creatinine (SCr). The right kidney was used for histopathological examination, while the left kidney was homogenized to assess the renal tissue levels of malondialdehyde (MDA), total antioxidant capacity (TAOC), interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α), kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL).
DOX induces acute kidney injury was demonstrated by significant elevations in BUN, SCr, and CRP levels. DUL significantly lowered the levels of BUN, SCr, and CRP, and reduced the levels of blood inflammation markers, including NLR and MLR. Additionally, it resulted in a significant reduction in the renal tissue levels of MDA, IL-1β, and TNF-α, while the level of TAOC was significantly elevated. These findings were supported by histopathological assessments.
The present study indicates that DUL mitigates doxorubicin-induced kidney damage by reducing oxidative stress and inflammation.
本研究旨在确定度拉糖肽(DUL)对阿霉素(DOX)诱导的急性肾损伤(AKI)的抗炎和抗氧化作用。
28只雄性大鼠随机分为四组:阴性对照组(接受蒸馏水)、阳性对照组(接受蒸馏水和单剂量DOX)、DUL 0.2 mg/kg组(每周两次接受DUL 0.2 mg/kg且接受单剂量DOX)和DUL 0.6 mg/kg组(每周两次接受DUL 0.6 mg/kg且接受单剂量DOX)。所有DOX剂量(20 mg/kg)均在研究的第13天给予,所有治疗均腹腔注射14天。在第15天,处死大鼠,采集血液以测量全血细胞计数(CBC)、中性粒细胞/淋巴细胞比值(NLR)、单核细胞/淋巴细胞比值(MLR)和血小板/淋巴细胞比值(PLR)、C反应蛋白(CRP)、血尿素氮(BUN)和血清肌酐(SCr)。右肾用于组织病理学检查,左肾匀浆以评估肾组织中丙二醛(MDA)水平、总抗氧化能力(TAOC)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、肾损伤分子-1(KIM-1)和中性粒细胞明胶酶相关脂质运载蛋白(NGAL)。
DOX诱导的急性肾损伤表现为BUN、SCr和CRP水平显著升高。DUL显著降低了BUN、SCr和CRP水平,并降低了包括NLR和MLR在内的血液炎症标志物水平。此外,它还导致肾组织中MDA、IL-1β和TNF-α水平显著降低,而TAOC水平显著升高。这些发现得到了组织病理学评估的支持。
本研究表明,DUL通过减轻氧化应激和炎症来减轻阿霉素诱导的肾损伤。