Abstract
Possible Protective Effects of Probiotics and Prebiotics on Methotrexate-induced Myelosuppression in Male Rats
Background: Methotrexate (MTX) is a folate analogue that is widely used as chemotherapeutic and immunosuppressive agent, yet its clinical application is frequently limited by its significant toxicity on rapidly dividing cells, particularly bone marrow (myelosuppression).
Recent evidence suggests that modulating the gut microbiome may offer a therapeutic pathway to mitigate chemotherapy-induced toxicity. Investigating specific microbial interventions could provide a novel approach to preserve bone marrow function during MTX treatment.
Aim: This study aimed to evaluate the possible protective effects of the probiotic Lactobacillus fermentum and the prebiotic inulin against methotrexate (MTX)-induced myelosuppression in a male Wistar rat model.
Methods:
36 male Wistar rats were divided into 6 groups and administered designated dosing protocols as follow:
• Group 1 (Control group): daily oral gavage of normal saline for 12 days and single I.P. injection of normal saline on day 8.
• Group 2 (Induction group): daily oral gavage of normal saline for 12 days and single I.P injection methotrexate (20 mg/kg) on day 8.
• Group 3 (Probiotic): daily oral gavage of Lactobacillus fermentum (1x10⁹ CFU) for 12 days and single I.P injection of normal saline on day 8.
• Group 4 (MTX + Probiotic): daily oral gavage of Lactobacillus fermentum (1x10⁹ CFU) for 12 days and single I.P injection of MTX (20 mg/kg) on day 8.
• Group 5 (Prebiotic): daily oral gavage of inulin (500 mg/kg) for 12 days and single I.P injection of normal saline on day 8.
• Group 6 (MTX + Prebiotic): daily oral gavage of inulin (500 mg/kg) for 12 days and single I.P injection of MTX (20 mg/kg) on day 8.
Biomarkers evaluated:
• Complete Blood Count (CBC)
• Oxidative Stress (MDA, GSH)
• Pro-inflammatory Cytokines (IL-6, TNF-α)
• Protein expression of caspase-3 and NF-κB
• Histopathological examination of bone marrow tissue
Statistical analysis of the data was performed using SPSS, data presented as Mean ± Standard deviation (SD); and one-way analysis of variance (ANOVA) used to determine the significance of the interventions across the respective groups.
| Intend to be published in the IJPS ? | NO |
|---|---|
| Has the manuscript been published | not published |
