Effects of oxaliplatin on inflammation and intestinal floras in rats with colorectal cancer

Colorectal Cancer
06/11/2020

Eur Rev Med Pharmacol Sci. 2020 Oct;24(20):10542-10549. doi: 10.26355/eurrev_202010_23407.

ABSTRACT

OBJECTIVE: The aim of this study was to investigate the effects of oxaliplatin on intestinal floras, inflammation level, apoptosis-related gene expressions and oxidative stress in rats with colorectal cancer.

MATERIALS AND METHODS: A total of 30 adult Sprague-Dawley (SD) rats were selected as research objects and were divided into control group, model group and oxaliplatin group. Rats in control group were raised normally, without any treatment. Rats in model group were subcutaneously injected with dimethylhydrazine (25 mg/kg) to establish the model of colorectal cancer. Meanwhile, rats in oxaliplatin group were injected with oxaliplatin (15 mg/kg) once every 2 weeks for 12 consecutive weeks. Peripheral blood, intestinal tumor tissues and feces were collected from rats. In addition, inflammatory indexes [tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), interleukin-4 (IL-4) and IL-1β], oxidative stress indexes [catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH) and total antioxidant capacity (T-AOC)], expressions of apoptosis-related genes [apoptotic protease activating factor-1 (Apaf1), Caspase-9, Survivin and B-cell lymphoma-2 (Bcl-2)] and intestinal floras were detected.

RESULTS: The abundance of microorganisms such as Sphaerobacterales, Adlercreutzia and Coriobacterium glomerans increased significantly in the intestines in control group (p<0.05). However, the abundance of Bifidobacterium, Rikenellaceae and Paraprevotella in the intestines was obviously higher in model group (p<0.05). Oxaliplatin group exhibited remarkably higher abundance of such microorganisms as Cyanobacteria, Alistipes and Metascardovia in rat intestines (p<0.05). The content of Alistipes was the highest in oxaliplatin group, followed by control group and model group, and the difference was statistically significant (p<0.05). The levels of serum TNF-α, CRP and IL-1β were remarkably higher in model group than those in control group (p<0.05). Oxaliplatin group exhibited notably lower levels of serum TNF-α, CRP and IL-1β (p<0.05) and higher IL-4 level than model group (p<0.05). The content of serum CAT, SOD, GSH and T-AOC was markedly elevated in model group compared with control group (p<0.05). However, it was significantly reduced in oxaliplatin group in comparison with model group (p<0.05). Compared with control group, model group had distinctly lower expressions of Apaf1, Caspase-9 and Survivin but an evidently higher expression level of Bcl-2 in tumor tissues (p<0.05). Moreover, the expressions of Apaf1, Caspase-9 and Survivin were clearly higher, while that of Bcl-2 was prominently lower in tumor tissues in oxaliplatin group than model group (p<0.05).

CONCLUSIONS: Oxaliplatin exerts significant effects on the inflammation, oxidative stress, apoptosis-related genes and intestinal floras in rats with CRC.