Abstract
Cyclophosphamide (CTX), a clinically important antineoplastic drug, also leads to some side effects such as nausea, vomiting and diarrhea in the consumer. In this study, Lactobacillus plantarum (L. plantarum) KLDS1.0318 preserved in our laboratory was orally administered to CTX-treated mice to explore its potential effects to attenuate the toxic effects of CTX-induced by modulating intestinal immune response, promoting intestinal integrity and improving metabolic profile. BALB/c mice were randomly divided into six groups including normal control group (NC; non-CTX with sterile saline), model control group (MC; CTX-treated with sterile saline), CTX-treated with L. plantarum KLDS1.0318 (10 mL/kg) groups with three different doses (KLDS1.0318-L, 5 × 107 CFU/mL; KLDS1.0318-M, 5 × 108 CFU/mL; KLDS1.0318-H, 5 × 109 CFU/mL), and CTX-treated with levamisole hydrochloride (40 mg/kg) as a positive control (PC) group. After receiving the bacterium for 20 days, samples of small intestine and colonic contents were collected for different analyses. The results revealed that the levels of cytokines secreted by Th1 cells (IL-2, IFN-γ, and TNF-α) and Th2 cells (IL-4, IL-6, and IL-10) in probiotic treatment groups were significantly higher than those in the MC group. Histopathological results showed that L. plantarum KLDS1.0318 favorably recovered CTX-induced abnormal intestinal morphology by improving the villus height and crypt depth as well as quantity of goblet cells and mucins production. Compared to CTX alone-treated group, the production of short-chain fatty acids (SCFAs) were significantly increased and the levels of pH and ammonia were decreased significantly with high dose L. plantarum KLDS1.0318 supplementation. Compared with mice in CTX alone-treated group, mice in three groups of KLDS1.0318 had increased Bifidobacterium and Lactobacillus and decreased Escherichia and Enterococcus in their cecal content. The present findings suggested that L. plantarum KLDS1.0318 could be of significant advantage to mitigate the harmful effects of CTX and improve the intestinal health in mice.
Highlights
Cyclophosphamide (CTX) belongs to the oxazaphosphorine family of mustard-alkylating agents
Comparison of the nucleotide sequence of 16S rRNA gene of the strain KLDS1.0318 in National Centre for Biotechnology Information (NCBI) showed that it belonged to the genus L. plantarum
It is noted that 5 × 109 colony forming units (CFU)/mL of bacterium treatment (KLDS1.0318-H) achieved maximum amelioration against CTXinduced increase in the levels of cytokines in mice
Summary
Cyclophosphamide (CTX) belongs to the oxazaphosphorine family of mustard-alkylating agents. It is one of the most successful antineoplastic agents synthesized in 1958 by Norbert Brock (Arnold et al, 1958; Madondo et al, 2016). Even today, owning to its direct cytotoxic effect on cancer cells, CTX is still remains one of the few chemotherapeutic drugs used to treat a range of cancers including lymphomas and solid tumors (breast cancer, ovarian cancer etc.) (Baumann and Preiss, 2001). CTX is an effective immunosuppressive agent and widely used in blood and marrow transplantation (BMT) and for the treatment of patients with a variety of autoimmune disorders (Perini et al, 2007; Uber et al, 2010). For recovering compromised epithelial barrier and reducing the side effects of chemotherapy drugs, new therapeutic options including probiotics and peptides are evolving (Baumgart and Dignass, 2002; Prisciandaro et al, 2011)
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