Clarithromycin attenuates cyclophosphamide-induced mucositis in mice

Abstract

No universally recognized agent is available for prophylaxis or therapy of mucositis induced by chemotherapy or chemo-radiotherapy. The effect of clarithromycin on the severity of mucositis induced by cyclophosphamide was investigated using a mouse model. Four cross-sections of small intestine (levels A, B, C, and D) were taken at equivalent intervals at day 5 after cyclophosphamide (400 mg kg-1) administration. The sections were stained with haematoxylin and eosin, and were graded for the degree of mucositis histologically. At section level B, the number of mice with no mucositis (grade 0) in the clarithromycin group was significantly greater than that in the ceftriaxone group (P < 0.05). At levels B and C, the number of mice with no mucositis (grade 0) in the clarithromycin group was significantly greater than that in the normal saline (NS) group (P < 0.05). At level C, the number of mice with grade 2 mucositis in the ceftriaxone group was significantly greater than that in the NS group (P < 0.05). When the number of sections at all levels were analyzed together, the number of mice with no mucositis (grade 0) in the clarithromycin group was significantly greater than that in the ceftriaxone and NS groups (P < 0.05). The present observation suggests that clarithromycin and ceftriaxone attenuates and aggravates cyclophosphamide-induced mucositis. It prompts clinical trials in bone marrow transplant (BMT) recipients receiving cyclophosphamide for conditioning, and reconsideration in the use of ceftriaxone in the treatment of neutropenic fever in BMT recipients. (C) 2000 Academic Press.