Nanocomposite Treatment Reduces Disease and Lethality in a Murine Model of Acute Graft-versus-Host Disease and Preserves Anti-Tumor Effects

Abstract

Graft versus host disease (GVHD) is an immunological disorder triggered by bone marrow transplantation that affects several organs, including the gastrointestinal tract and liver. Fullerenes and their soluble forms, fullerols, are nanocomposites with a closed symmetrical structure with anti-inflammatory and anti-oxidant properties. The present study evaluated the effects of treatment with the fullerol (C60(OH)18-20) in the development and pathogenesis of GVHD in a murine model. Mice with experimental GVHD that were treated with the fullerol showed reduced clinical signs of disease and mortality compared with untreated mice. Treatment with the fullerol decreased the hepatic damage associated with reduced hepatic levels of reactive oxygen species, pro-inflammatory cytokines and chemokines (IFN-γ TNF-α, CCL2, CCL3 and CCL5) and reduced leukocyte accumulation. The amelioration of GVHD after treatment with the fullerol was also associated with reduced intestinal lesions and consequent bacterial translocation to the blood, liver and peritoneal cavity. Moreover, the fullerol treatment alleviated the GVHD while preserving effects of the graft against a leukemia cell line (GFP+P815). In summary, the fullerol was effective in reducing the GVHD inflammatory response in mice and may suggest novel ways to treat this disease.

Treatment with Apocynin Limits the Development of Acute Graft-versus-Host Disease in Mice

“…Because of the toxicity of the high level of body irradiation, the recipient mice received an oral suspension of ciprofloxacin (70 mg/l) in their drinking water from 1 d before to 15 d after transplantation. The BM cells and splenocytes were isolated as previously described [13, 25].…”

“…In a previous study, we have shown an increase in ROS in the mouse liver subjected to GVHD. Based on the elimination of GVHD after treatment with fullerol, a nanocomposite with antioxidant properties [13], we hypothesized that ROS seems to be involved in the establishment of GVHD. Despite the evidence of ROS involvement in the pathogenesis of GVHD, description of the effects of GVHD treatment on dinucleotide phosphate oxidase (NOX)-derived ROS production is still lacking.…”

Inhibition of 5-lipoxygenase alleviates graft-versus-host disease

“…Because of the toxicity of the high level of body irradiation, the recipient mice received an oral suspension of ciprofloxacin (70 mg/L) in their drinking water from 1 d before to 15 d after transplantation. The BM cells and splenocytes were isolated as previously described ( Rezende et al, 2013 ; Bernardes et al, 2015 ). Recipient mice were monitored for survival and clinical GVHD symptoms and were sacrificed for blinded histopathologic and flow cytometric analysis as previously described ( Rezende et al, 2013 ; Bernardes et al, 2015 ).…”

“…Recipient mice were evaluated clinically with a standard scoring system as previously described (maximum index = 14; Rezende et al, 2013 ; Bernardes et al, 2015 ). Scores were according to weight loss, posture (hunching), activity, fur texture, skin integrity, diarrhea, and fecal occult blood.…”

Sorption Detoxification as an Addition to Conventional Therapy of Acute Radiation Sickness and Iatrogenic Leukopenia

“…Sandhir R. et al [36] believe that nanoantioxidants (inorganic nanoparticles possessing intrinsic antioxidant properties) would be more effective against [37]. The aftertreatment with the same nanocomposite ameliorates the graft-versus-host disease reactions in mice and reduces intestinal lesions and bacterial translocation; prevents mortality and morbidity [38]. Nano-fullerenes promote osteogenesis of human adipose-derived stem cells and possess a great antioxidant capacity [39].…”