Faculty of Science and Technology, Department of Zoology, Government College Women University, Faisalabad, Punjab, Pakistan.
Institute of Zoology, University of the Punjab, Lahore, Punjab, Pakistan.
PLoS One. 2023 Aug 25;18(8):e0290668. doi: 10.1371/journal.pone.0290668. eCollection 2023.
The constant use of disease modifying anti rheumatic drugs affects the functioning of multiple organs inside the body. Some drugs are more toxic than others. The present case control investigation was designed to evaluate the comparative toxicity of methotrexate and leflunomide on multiple organs in rheumatoid arthritis patients. For this purpose, 100 subjects with confirmed rheumatoid arthritis condition were recruited form tertiary care center. Whereas 50 age matched controls were recruited from the local healthy population. Participants of the study were categorized into three groups with equal numbers of subjects in each group (n = 50). Group 1 comprised rheumatoid arthritis patients on methotrexate treatment, group 2 included rheumatoid arthritis patients on leflunomide treatment and group 3 were healthy subjects. Cardiac and respiratory response was evaluated by monitoring blood pressure, pulse and breathing rate and spot oxygen saturation. Stress on liver was estimated by measuring change in liver enzymes (alanine transaminase, aspartate aminotransferase, and alkaline phosphatase) and total bilirubin. While, degree of renal impairment was assessed by calculating glomerular filtration rate, serum creatinine, urinary urea and uric acid. For statistical interpretation, data was subjected to independent student "t" test and analysis of variance (one way ANOVA) for mean variations. Both methotrexate and leflunomide elevated the systolic and diastolic blood pressure and pulse rate. Leflunomide maintained the oxygen saturation at 96.7%, whereas methotrexate exerted serious effect on spot oxygen saturation by reducing it significantly to 93.25% than healthy subjects. Hepatotoxicity manifested by sustained use of leflunomide was perceptible in this study group. Whereas, both methotrexate and leflunomide influenced renal function as indicated by marked increase in blood urea nitrogen (P = 0.001), serum creatinine (P = 0.007) and reduced glomerular filtration rate (P<0.0001). However, use of methotrexate demonstrated significant (P<0.0001) reduction in serum uric acid and urinary urea levels. Methotrexate is more injurious to heart, blood vessels and kidneys than leflunomide but it is less noxious to hepatic parenchyma. Contrarily, leflunomide usage is comparatively better option for respiratory, cardiovascular, and renal health but dangerous to liver. Thus, a single drug can't be prescribed for the treatment of rheumatoid arthritis for longer management of arthritis patients.
长期使用疾病修饰抗风湿药物会影响体内多个器官的功能。一些药物比其他药物更具毒性。本病例对照研究旨在评估甲氨蝶呤和来氟米特对类风湿关节炎患者多个器官的比较毒性。为此，从三级保健中心招募了 100 名确诊为类风湿关节炎的患者作为研究对象。同时，从当地健康人群中招募了 50 名年龄匹配的对照者。将研究参与者分为三组，每组人数相等（n = 50）。第 1 组为接受甲氨蝶呤治疗的类风湿关节炎患者，第 2 组为接受来氟米特治疗的类风湿关节炎患者，第 3 组为健康受试者。通过监测血压、脉搏和呼吸频率以及血氧饱和度来评估心脏和呼吸反应。通过测量肝酶（丙氨酸氨基转移酶、天冬氨酸氨基转移酶和碱性磷酸酶）和总胆红素的变化来估计肝应激。同时，通过计算肾小球滤过率、血清肌酐、尿尿素和尿酸来评估肾功能损害程度。为了进行统计解释，对数据进行了独立学生“t”检验和方差分析（单因素方差分析），以分析均值变化。甲氨蝶呤和来氟米特均升高了收缩压和舒张压以及脉搏率。来氟米特将氧饱和度维持在 96.7%，而甲氨蝶呤通过将其显著降低至 93.25%，与健康受试者相比，对血氧饱和度产生了严重影响。本研究组发现来氟米特持续使用引起的肝毒性。然而，甲氨蝶呤和来氟米特均会影响肾功能，表现为血尿素氮（P = 0.001）、血清肌酐（P = 0.007）显著增加和肾小球滤过率降低（P<0.0001）。然而，甲氨蝶呤的使用显著降低了血清尿酸和尿尿素水平（P<0.0001）。与来氟米特相比，甲氨蝶呤对心脏、血管和肾脏的损害更大，但对肝实质的毒性较小。相反，来氟米特的使用是治疗类风湿关节炎的更好选择，对呼吸、心血管和肾脏健康有益，但对肝脏有害。因此，对于关节炎患者的长期管理，不能仅开一种药物来治疗类风湿关节炎。
