Sodium Alginate Inhibits Methotrexate-Induced Gastrointestinal Mucositis in Rats

Abstract

Gastrointestinal mucositis is one of the most prevalent side effects of chemotherapy. Methotrexate is a pro-oxidant compound that depletes dihydrofolate pools and is widely used in the treatment of leukemia and other malignancies. Through its effects on normal tissues with high rates of proliferation, methotrexate treatment leads to gastrointestinal mucositis. In rats, methotrexate-induced gastrointestinal mucositis is histologically characterized by crypt loss, callus fusion and atrophy, capillary dilatation, and infiltration of mixed inflammatory cells. The water-soluble dietary fiber sodium alginate (AL-Na) is derived from seaweed and has demonstrated muco-protective and hemostatic effects on upper gastrointestinal ulcers. In the present study, we evaluated the effects of AL-Na on methotrexate-induced small intestinal mucositis in rats. Animals were subcutaneously administered methotrexate at a dosage of 2.5 mg/kg once daily for 3 d. Rats were treated with single oral doses of AL-Na 30 min before and 6 h after methotrexate administration. On the 4th day, small intestines were removed and weighed. Subsequently, tissues were stained with hematoxylin-eosin and bromodeoxyuridine. AL-Na significantly prevented methotrexate-induced small intestinal mucositis. Moreover, AL-Na prevented decreases in red blood cell numbers, hemoglobin levels, and hematocrit levels. These results suggest the potential of AL-Na as a therapy for methotrexate-induced small intestinal mucositis.

Effect of Methotrexate on the Jejunum of Adult Albino Rat and the Possible Protective Role of Vitamin A: Histological and Immunohistochemical Study

“…In the current work, most of the villi were covered with flattened or cuboidal cells in long term methotrexate treated group (group IV) as previously reported [18]. This might be related to the antimitotic effect of MTX with wide spread apoptosis of the stem cells in the villus tip [16].…”

“…This was in agreement with Jahovic et al [21] who found desquamation of surface epithelium in rats treated with MTX. Some authors [5] suggested that this finding was due to the cytotoxic effect of MTX on the intestinal cells while others [18] related it to the inhibition of the cell proliferation in the small intestinal mucosa. The mucosal damage in the present study progressed to ulcer formation in long term methotrexate treated group (group IV).…”

Therapeutic effects of intra‐articular ultra‐purified low endotoxin alginate administration on an experimental canine osteoarthritis model

“…A previous gastrointestinal study indicated that layers of alginate solution protected against tissue inflammation due to its expansion on the mucosal surface. 9 Although the present study showed no definite data clarifying the mechanism, further in vitro and in vivo studies will help us elucidate the therapeutic mechanism of UPLE-alginate against OA pathogenesis.…”

“…Alginate is a naturally abundant and anionic polysaccharide with homopolymeric blocks of (1–4)‐linked β‐D‐mannuronate and its C‐5 epimer α‐L‐gluronate residues. To date, alginate‐based materials have received considerable attention for clinical applications in various fields, including cartilage tissue engineering …”

“…To date, alginate-based materials have received considerable attention for clinical applications in various fields, including cartilage tissue engineering. [7][8][9][10] In particular, alginate has favorable effects on chondrogenesis and cartilage regeneration. 11,12 However, this biomaterial includes an issue relevant to mitogenic and cytotoxic impurities, that is, inducing a foreign-body reaction or heavy pericapsular fibrosis in a living body.…”