Abdelrahman Aly M, Al Maskari Raya, Ali Haytham, Manoj Priyadarsini, Al Suleimani Yousuf
Department of Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, P.O. Box 35, Muscat 123, Oman.
Department of Animal and Veterinary Sciences, College of Agricultural and Marine Sciences, Sultan Qaboos University, P.O. Box 35, Muscat 123, Oman.
Biology (Basel). 2025 Feb 6;14(2):161. doi: 10.3390/biology14020161.
Riociguat is a soluble guanylate cyclase (sGC) activator that increases the levels of cyclic guanosine monophosphate (cGMP). cGMP is known to play a key role in regulating kidney function. This research sought to investigate the possible protective effects of riociguat on the kidneys in the context of chronic kidney disease (CKD). CKD was induced in male Wistar rats through adenine administration. A total of 24 rats were allocated into four groups and administered treatments over a period of 35 days. Group 1 received a normal diet and a vehicle (carboxymethylcellulose (0.5%)), serving as the control. Group 2 received adenine (0.25% /) in the feed and a vehicle. Groups 3 and 4 received adenine in the feed (0.25% /) plus riociguat (3 mg/kg/day) and riociguat (10 mg/kg/day), respectively. Adenine administration significantly elevated systolic blood pressure, plasma creatinine, urea, and neutrophil gelatinase-associated lipocalin (NGAL). Furthermore, adenine reduced creatinine clearance and increased the urinary albumin-to-creatinine ratio and urinary N-Acetyl-β-D-Glucosaminidase (NAG). Histopathologically, adenine caused renal tubular necrosis and fibrosis. Furthermore, adenine elevated the plasma concentration of interleukins (IL-1β and IL-6) and tumor necrosis factor-alpha (TNF-α). Adenine significantly increased renal malondialdehyde (MDA) and reduced glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), and total antioxidant capacity (TAC). Treatment with riociguat attenuated adenine-induced hypertension, improved kidney function, and ameliorated histopathological changes. Riociguat also reduced kidney injury markers, inflammation, and renal oxidative stress. The renoprotective effect of riociguat is probably due to anti-inflammatory and antioxidant actions. This indicates that riociguat may have the potential to slow the progression of kidney damage in chronic kidney disease (CKD).
利奥西呱是一种可溶性鸟苷酸环化酶（sGC）激活剂，可提高环磷酸鸟苷（cGMP）水平。已知cGMP在调节肾功能中起关键作用。本研究旨在探讨利奥西呱在慢性肾脏病（CKD）背景下对肾脏可能的保护作用。通过给雄性Wistar大鼠喂食腺嘌呤诱导CKD。总共24只大鼠被分为四组，并在35天内给予不同处理。第1组接受正常饮食和赋形剂（羧甲基纤维素（0.5%）），作为对照。第2组在饲料中接受腺嘌呤（0.25%/）和赋形剂。第3组和第4组分别在饲料中接受腺嘌呤（0.25%/）加 利奥西呱（3毫克/千克/天）和利奥西呱（10毫克/千克/天）。给予腺嘌呤显著升高了收缩压、血浆肌酐、尿素和中性粒细胞明胶酶相关脂质运载蛋白（NGAL）。此外，腺嘌呤降低了肌酐清除率，并增加了尿白蛋白与肌酐比值以及尿N-乙酰-β-D-氨基葡萄糖苷酶（NAG）。组织病理学上，腺嘌呤导致肾小管坏死和纤维化。此外，腺嘌呤升高了白细胞介素（IL-1β和IL-6）和肿瘤坏死因子-α（TNF-α）的血浆浓度。腺嘌呤显著增加了肾丙二醛（MDA）并降低了谷胱甘肽还原酶（GR）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和总抗氧化能力（TAC）。用利奥西呱治疗可减轻腺嘌呤诱导的高血压，改善肾功能，并减轻组织病理学变化。利奥西呱还降低了肾损伤标志物、炎症和肾脏氧化应激。利奥西呱的肾脏保护作用可能归因于抗炎和抗氧化作用。这表明利奥西呱可能具有减缓慢性肾脏病（CKD）肾损伤进展 的潜力。
