Inhibition of alternative complement system and prolyl hydroxylase ameliorates anaemia of inflammation.

IF 4.6 2区医学 Q2 IMMUNOLOGY

Inflammopharmacology Pub Date : 2024-11-23 DOI:10.1007/s10787-024-01592-y

Vishal J Patel, Amit A Joharapurkar, Samadhan G Kshirsagar, Maulik S Patel, Hardikkumar H Savsani, Milan H Rakhasiya, Harshad S Dodiya, Mukul R Jain

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引用次数: 0

Abstract

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.

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抑制替代补体系统和脯氨酰羟化酶可改善炎症性贫血。

与炎症相关的慢性疾病会导致红细胞的早期破坏。先天性免疫的一部分--补体系统参与了这种红细胞破坏。持续的炎症会造成肾损伤，导致促红细胞生成素释放减少和功能性缺铁，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 desidustat 对肽聚糖多糖（PGPS）治疗诱发大鼠贫血的影响。在接受 PGPS 治疗三天后，对炎症、溶血及其诊断指标（LDH、总胆红素和红细胞寿命）进行了评估。挑战 PGPS 14 天后，对血红蛋白、红细胞、铁稳态和红细胞破坏进行了评估。在给予 PGPS 的同时还给予地舒司他（15 毫克/千克）和依他昔潘（20 毫克/千克），并持续两周。依帕可潘及其与地西司他的联合治疗可预防 LDH、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日恢复正常。联合用药还能降低白细胞、碱性磷酸酶、天冬氨酸氨基转移酶和大鼠爪体积。地舒司他及其复方制剂可增加血清铁。联合治疗可降低脾脏重量、组织铁和血清血红素。单独使用地司他对铁（血清和组织）和血红素的影响突出。因此，联合使用依帕可潘和地西司他可能是治疗炎症性贫血的一种有效疗法。

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来源期刊

Inflammopharmacology IMMUNOLOGYTOXICOLOGY-TOXICOLOGY

CiteScore

8.00

自引率

3.40%

发文量

200

期刊介绍： Inflammopharmacology is the official publication of the Gastrointestinal Section of the International Union of Basic and Clinical Pharmacology (IUPHAR) and the Hungarian Experimental and Clinical Pharmacology Society (HECPS). Inflammopharmacology publishes papers on all aspects of inflammation and its pharmacological control emphasizing comparisons of (a) different inflammatory states, and (b) the actions, therapeutic efficacy and safety of drugs employed in the treatment of inflammatory conditions. The comparative aspects of the types of inflammatory conditions include gastrointestinal disease (e.g. ulcerative colitis, Crohn''s disease), parasitic diseases, toxicological manifestations of the effects of drugs and environmental agents, arthritic conditions, and inflammatory effects of injury or aging on skeletal muscle. The journal has seven main interest areas: -Drug-Disease Interactions - Conditional Pharmacology - i.e. where the condition (disease or stress state) influences the therapeutic response and side (adverse) effects from anti-inflammatory drugs. Mechanisms of drug-disease and drug disease interactions and the role of different stress states -Rheumatology - particular emphasis on methods of measurement of clinical response effects of new agents, adverse effects from anti-rheumatic drugs -Gastroenterology - with particular emphasis on animal and human models, mechanisms of mucosal inflammation and ulceration and effects of novel and established anti-ulcer, anti-inflammatory agents, or antiparasitic agents -Neuro-Inflammation and Pain - model systems, pharmacology of new analgesic agents and mechanisms of neuro-inflammation and pain -Novel drugs, natural products and nutraceuticals - and their effects on inflammatory processes, especially where there are indications of novel modes action compared with conventional drugs e.g. NSAIDs -Muscle-immune interactions during inflammation [...]