Steamed root of Rehmannia glutinosa Libosch (Plantaginaceae) alleviates methotrexate-induced intestinal mucositis in rats

Abstract

Ethnopharmacological relevance: Intestinal mucositis induced by chemotherapy is a severe clinical problem in cancer patients that currently lack effective interventions. In traditional Chinese medicine, chemotherapeutic toxicity is diagnosed as Qi and Yin deficiency, and steamed rehmannia root (SRR) is frequently prescribed to these patients. Whether SRR can prevent the adverse effects remains to be confirmed experimentally. The present study used a rat model to investigate potential efficacy and action mechanisms of SRR in attenuating the adverse effects caused by chemotherapy.

Materials and methods: Intraperitoneal injection of a single dose of anti-metabolite methotrexate (MTX, 25mg/kg) was given to adult Wistar rats, which also received oral gavage of water or SRR (1.08g/kg twice daily 3 days before and 4 days after MTX treatment), or calcium folinate (CF, a clinically used MTX antidote as a comparison, at 1mg/kg twice daily 36h after MTX treatment), or SRR and CF in combination. Animals were sacrificed 4 days after MTX treatment. Complete blood cell counting was carried out. Jejunum was analyzed histologically for mucosal damage, immunohistochemically for proliferating cell nuclear antigen (PCNA), and biochemically for thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH), as well as for tumor necrosis factor alpha (TNF-α).

Results: MTX treatment led to weight loss, leucopenia, polycythemia, increase in large thrombocyte ratio, intestinal villus atrophy, crypt loss and reduction in PCNA positive crypt cells, increases in mucosal TBARS and TNF-α and decrease in GSH. All these alterations were inhibited by SRR administration except leucopenia, and the effects of CF or CF plus SRR supplementation were found to be inferior to those of SRR.

Conclusions: SRR can alleviate MTX-induced gut mucositis, which may be achieved by inhibiting MTX-induced oxidative stress and inflammatory response. These findings support the application of SRR in chemotherapy but not the combined application of SRR and CF.

Keywords: Calcium folinate; Chemotherapy; Leucopenia; Methotrexate; Mucositis; Rehmannia glutinosa.