Methotrexate [KLH]

Objective: The long-term sequelae of methotrexate (MTX) remain the major cause of concern for both patients and therapists. Therefore, new approaches to decrease MTX side effects are needed. The study was carried out to evaluate the effects of Iris songarica Schrenk (IS) rhizome extract against MTX-induced hepatic and renal injuries in rats. Materials and Methods: Forty male Wistar rats were randomly divided into five groups (n=8) including control, MTX, IS50, IS150 and IS300. Control and MTX groups were only treated orally with saline; whereas, IS50, IS150 and IS300 groups were treated with IS extract at three different doses (50, 150, and 300 mg/kg, respectively). Besides, the MTX and experimental groups were received a single dose of MTX (20 mg/kg) intraperitoneally on day 4. On the ninth day, animals were sacrificed, blood transaminases, urea and creatinine were assessed and the concentration of malondialdehyde (MDA) and the activity of super-oxide dismutase (SOD) were determined in both liver and kidney tissues. Moreover, hepatic and renal damages were evaluated histopathologically. Results: MTX by increasing oxidative stress (MDA) and decreasing antioxidant capacity (SOD) induced hepatic and renal damages as confirmed by biochemical and histological parameters analyses. However, treatment with IS caused significant improvements in hepatic and renal histological architectures and SOD activity (p<0.01) along with reducing liver enzymes, urea, creatinine and MDA (p<0.01). Conclusion: The results of the present study showed that IS extract through antioxidant and probably anti-inflammatory activities, could effectively limit MTX-induced hepatic and renal injuries in rats.

Rationale: Methotrexate-associated lymphoproliferative disorder (MTX-LPD) is a serious complication in patients treated using methotrexate. It occasionally develops in extra-nodal sites, but rarely in the central nervous system (CNS) or in 2 different sites at the same time. We present the rare case of a patient with rheumatoid arthritis who developed lymphoma in the CNS and stomach during MTX therapy. Patient concerns: A 75-year-old Japanese man with rheumatoid arthritis who received methotrexate was admitted to our hospital because of gait ataxia and anorexia. Diagnoses: Imaging findings and biopsy led to a diagnosis of 2 different types of MTX-LPD in the central nervous system and stomach. Interventions: The lesion in his stomach improved after methotrexate withdrawal, whereas the cerebellar mass required highdose methotrexate and rituximab therapy. Outcomes: Complete remission has been maintained for the 2 years following the initiation of chemotherapy. Lessons: In patients with RA who receive MTX and develop new neurological symptoms, CNS lymphoma as an MTX-LPD may be considered as a differential diagnosis.