Hakimizadeh Elham, Zamanian Mohammad Yassin, Damankhorshid Morteza, Giménez-Llort Lydia, Sciorati Clara, Nikbakhtzadeh Marjan, Moradbeygi Khadijeh, Kujawska Małgorzata, Kaeidi Ayat, Taghipour Zahra, Fatemi Iman
Physiology-Pharmacology Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
Department of Physiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Fundam Clin Pharmacol. 2022 Aug;36(4):721-730. doi: 10.1111/fcp.12766. Epub 2022 Mar 15.
Calcium dobesilate (CaD) is used for the treatment of diabetic retinopathy and nephropathy. This agent exerts antioxidant effects. In the present study, we evaluated the protective effects of oral administration of CaD against hepatorenal damages in a mice model of aging induced by d-galactose (d-gal). We used 28 male albino mice, which equally and randomly were divided into four groups as follows: intact, aging (d-gal at the dose of 500 mg/kg, p.o.), aging + CaD 50 (d-gal plus CaD at the dose of 50 mg/kg), and aging + CaD 100 (d-gal plus CaD at the dose of 100 mg/kg, p.o.). All drugs were administered orally once a day for 42 days. The liver and kidney damages were evaluated by measuring mass indices, levels of serum creatinine and blood urea nitrogen, and activities of serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase and by histopathological evaluation. Moreover, hepatic and renal tissue oxidant/antioxidant markers (malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase) were measured. The results showed that d-gal treatment induced significant oxidative stress in the kidney and liver that was paralleled by dysfunctions and histological alterations of these organs. CaD significantly improved the liver and kidney indices, implemented functional capacity of the liver and kidney, as well as decreased oxidative stress enhancing antioxidative enzyme activities. CaD treatment also inhibited the development of histological alterations of both kidney and liver. CaD might represent a promising therapeutic agent for the attenuation of hepatorenal injuries induced by aging.
羟苯磺酸钙(CaD)用于治疗糖尿病视网膜病变和肾病。该药物具有抗氧化作用。在本研究中,我们评估了口服CaD对d-半乳糖(d-gal)诱导的衰老小鼠模型肝肾损伤的保护作用。我们使用了28只雄性白化小鼠,将其平均随机分为四组:完整组、衰老组(口服500 mg/kg剂量的d-gal)、衰老+CaD 50组(d-gal加50 mg/kg剂量的CaD)和衰老+CaD 100组(d-gal加100 mg/kg剂量的CaD,口服)。所有药物均每日口服一次,持续42天。通过测量质量指数、血清肌酐和血尿素氮水平、血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶和碱性磷酸酶活性以及组织病理学评估来评估肝肾损伤。此外,还测量了肝和肾组织的氧化/抗氧化标志物(丙二醛、超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶)。结果表明,d-gal处理在肾脏和肝脏中诱导了显著的氧化应激,同时伴有这些器官的功能障碍和组织学改变。CaD显著改善了肝脏和肾脏指数,提高了肝脏和肾脏的功能能力,同时降低了氧化应激,增强了抗氧化酶活性。CaD处理还抑制了肾脏和肝脏组织学改变的发展。CaD可能是一种有前景的治疗药物,可减轻衰老引起的肝肾损伤。