Patel Vishal J, Joharapurkar Amit A, Kshirsagar Samadhan G, Patel Maulik S, Savsani Hardikkumar H, Rakhasiya Milan H, Dodiya Harshad S, Jain Mukul R
Department of Pharmacology and Toxicology, Zydus Research Centre, Zydus Lifesciences Limited, Sarkhej Bavla NH 8A, Moraiya, Ahmedabad, 382210, India.
Inflammopharmacology. 2025 Feb;33(2):825-832. doi: 10.1007/s10787-024-01592-y. Epub 2024 Nov 23.
Chronic diseases associated with inflammation cause early destruction of RBCs. Complement system, part of innate immunity, is involved in such RBC destruction. Persistent inflammation causes kidney injury, leading to reduced erythropoietin release and functional iron deficiency, causing anaemia. We have investigated effect of iptacopan, a factor B inhibitor, and desidustat, a prolyl hydroxylase inhibitor in anaemia induced by peptidoglycan polysaccharide (PGPS) treatment in rats. Inflammation, haemolysis and its diagnostic markers (LDH, total bilirubin, and RBC lifespan) were evaluated after three days of PGPS challenge. Haemoglobin, RBC, iron homeostasis, and RBC destruction were evaluated fourteen days after PGPS challenge. Desidustat (15 mg/kg) and iptacopan (20 mg/kg) were given along with PGPS and continued for two weeks. Iptacopan and its combination with desidustat prevented LDH, total bilirubin, complement protein-C3a and haemolysis. Combination treatment caused an early normalization of haemoglobin and RBC. Combination also reduced WBC, alkaline phosphatase, aspartate aminotransferase, and rat paw volume. Serum iron was increased by desidustat and its combination treatment. Spleen weight, tissue iron, and serum hepcidin were reduced by combination treatment. Effect of desidustat alone was prominent on iron (serum and tissue) and hepcidin. Thus, combination of iptacopan and desidustat can be a potentially useful therapeutic option for treatment of anaemia of inflammation.
与炎症相关的慢性疾病会导致红细胞早期破坏。补体系统作为固有免疫的一部分，参与了这种红细胞破坏过程。持续性炎症会导致肾损伤，进而导致促红细胞生成素释放减少和功能性铁缺乏，从而引起贫血。我们研究了B因子抑制剂iptacopan和脯氨酰羟化酶抑制剂地西司他对肽聚糖多糖（PGPS）诱导的大鼠贫血的影响。在PGPS攻击三天后评估炎症、溶血及其诊断标志物（乳酸脱氢酶、总胆红素和红细胞寿命）。在PGPS攻击十四天后评估血红蛋白、红细胞、铁稳态和红细胞破坏情况。iptacopan（20mg/kg）和地西司他（15mg/kg）与PGPS一起给药，并持续两周。iptacopan及其与地西司他的联合用药可预防乳酸脱氢酶、总胆红素、补体蛋白C3a和溶血。联合治疗可使血红蛋白和红细胞早期恢复正常。联合治疗还可降低白细胞、碱性磷酸酶、天冬氨酸转氨酶和大鼠爪体积。地西司他及其联合治疗可增加血清铁。联合治疗可降低脾脏重量、组织铁和血清铁调素。单独使用地西司他对铁（血清和组织）和铁调素的作用显著。因此，iptacopan和地西司他联合使用可能是治疗炎症性贫血的一种潜在有效治疗选择。
