Intestinal Permeability in the Assessment of Intestinal Toxicity of Cytotoxic Agents

Abstract

The diagnosis and assessment of the severity of intestinal mucosal damage in cancer patients treated with cytotoxic drugs still rely on anamnestic data. There is cumulative evidence that measurement of intestinal permeability may represent a sensitive indicator of intestinal damage by cytotoxic agents. The intestinal permeability testing is based on differential permeability of tight junctions along the crypt-villus axis to nonmetabolized sugars. Cytotoxic drugs induce flattening of villi, leading to increased exposure of luminal contents to crypts and increased disaccharide absorption. An increased disaccharide/monosaccharide ratio and decreased xylose absorption have been described in patients treated with different cytotoxic drugs across a spectrum of malignant tumors that correlated with clinical manifestations, and were used to monitor the effect of therapeutic interventions.

Neopterin as a biomarker of immune response in cancer patients

“…Paradoxically, with the exception of hematologic toxicity, the use of laboratory methods to predict or even monitor toxicity of anticancer therapy is still relatively limited. In many situations, e.g., mucosal or skin toxicity, the diagnosis and assessment of severity of symptoms still heavily relies on symptoms reported by the patients or on physical examination rather than on exact measurements (112)(113)(114).…”

“…Surprisingly, the assessment of this common toxicity is still based on the data obtained from the patients like the frequency of bowel movements (114). Different laboratory methods have been proposed for monitoring of gastrointestinal toxicity of anticancer agents.…”

Assessment of intestinal permeability in preruminant calves by lactulose/mannitol test

“…The probes passing through large pores have molecular radius up to 0.5 nm, whereas molecular radius of the probes passing through small pores is equal or less than 0.4 nm (Bjarnason et al, 2002). Some authors note even 3 types of pores in intestinal epithelia: 1. small pores up to 0.6 nm localized on the tips of the villi which are permeable only to monosoccharides and alditols, 2. large pores (5-6 nm) permeable to disccharides are localized in the crypts, and 3. the medium-sized pores (1-1.5 nm) are localized at the base of the villi (Melichar et al, 2005).…”

“…The mechanism predominantly responsible for transepithelial movement of monosaccharides is solvent drag originating from the hyperosmolarity of the villi tips (Melichar et al, 2005), whereas disaccharides pass intestinal mucosa paracellulary, by tight junctions. The paracellular transport is passive and results from diffusion, electrodiffusion, or osmosis down the gradients created by transcellular mechanisms (Anderson, 2001).…”

Neoadjuvant combination therapy with trastuzumab in a breast cancer patient with synchronous rectal carcinoma: a case report and biomarker study

“…Effects on tissues with highest mitotic activity, i.e. bone marrow and gastrointestinal mucosa, are associated with the two most common adverse events accompanying the administration of cytotoxic chemotherapy [23]. While laboratory methods can determine peripheral blood cell count as continuous variables allowing for a graded assessment and differential response to the changes induced by the treatment, the assessment of gastrointestinal toxicity still depends almost exclusively on the data reported by the patients that may be affected by subjective factors and are often impossible to verify.…”