Hydroferrate Fluid, MRN-100, Provides Protection against Chemical-Induced Gastric and Esophageal Cancer in Wistar Rats

Abstract

In the current study, we examined the protective effect of hydroferrate fluid MRN-100 against the carcinogen methylnitronitrosoguanidine (MNNG)-induced gastric and esophageal cancer in rats. MRN-100 is an iron-based compound composed of bivalent and trivalent ferrates. At 33 weeks post treatment with MNNG, rats were killed and examined for the histopathology of esophagus and stomach; liver, spleen, and total body weight; and antioxidant levels in the blood and stomach tissues. Results showed that 17/20 (85%) gastroesophageal tissues from carcinogen MNNG-treated rats developed dysplasia and cancer, as compared to 8/20 (40%) rats treated with MNNG plus MRN-100. In addition, MRN-100 exerted an antioxidant effect in both the blood and stomach tissues by increasing levels of GSH, antioxidant enzymes SOD, CAT, and GPx, and total antioxidant capacity (TAC) level. This was accompanied by a reduction in the total free-radical and malondialdehyde levels. Furthermore, MRN-100 protected against body and organ weight loss. Thus, MRN-100 exhibited significant cancer chemopreventive activity by protecting tissues against oxidative damage in rats, which may suggest its effectiveness as an adjuvant for the treatment of gastric/esophageal carcinoma.

DHA induces apoptosis of human malignant breast cancer tissues by the TLR‑4/PPAR‑α pathways

“…Numerous studies have reported that the upregulated expression or higher activity of AOEs may be used as effective strategies for cancer prevention and therapy. For example, MRN-100, as an adjuvant therapy was demonstrated to be effective in the treatment of esophageal/gastric carcinoma, exerting an antioxidant effect in the stomach and blood tissues by increasing the levels of GSH-PX, SOD, CAT, GSH-PX, and the total antioxidant capacity ( 29 ). Ganoderma lucidum significantly enhanced the levels of SOD, CAT and GPH-PX in the plasma, liver, and mammary tissues, thus being an effective chemopreventive agent against BC ( 30 ).…”

Potential role of MRN-100, an iron-based compound, in upregulating production of cytokine IL-10 in human dendritic cells to promote an anti-inflammatory response in vitro

“…26 Treatment with MRN-100 has been shown to provide protection to blood and stomach tissues in rats with methylnitronitrosoguanidine-induced esophageal and gastric cancer by the mechanism involved in increasing the levels of GSH; antioxidant enzymes CAT, SOD, and GPx; and total antioxidant capacity level, with an accompanying reduction in the total free radical and malondialdehyde levels. 27 Finally, MRN-100 has been shown to protect against oxidative stress–induced apoptosis of murine lymphocytes in vitro by preventing H 2 O 2 -induced downregulation of Bcl-2 and upregulation of Bax. 28 Other studies have also shown the protective effects of natural antioxidant agents: Myrtus communis extracts protected rats against liver injury and fibrosis following biliary obstruction via its antioxidant activities, 45 and mushrooms have been shown to support anti-inflammatory actions and, in turn, offer protection against obesity-related hypertension and dyslipidemia.…”

“…Our previous work has shown that Biobran/MGN-3 (an arabinoxylan rice bran), PFT (a novel kefir product), and Marina Crystal Minerals (MCM; a mixture of crystallized minerals and trace elements extracted from seawater) all promote the production of inflammatory and anti-inflammatory cytokines. 27,31,32 Biobran and PFT also stimulate DC-primed CD4+ T cell proliferation and their production of IL-10, and MCM causes the upregulation of co-stimulatory molecules CD86, CD80, and HLA-DR. In addition, DPV576 (a dispersed aqueous mixture composed of nanodiamond and nanoplatinum) activates human DCs and upregulates the levels of DC-secreted cytokine IL-10, 33 and we have recently observed that exposure of human CD4+ T lymphocytes to DPV576 inhibits the activity of the transient receptor potential vanilloid channel TRPV1 in CD4+ T lymphocytes, suggesting that it has the potential for use in pain management.…”

“…Being an iron-based compound, MRN-100 contains bivalent and trivalent ferrates isolated from phytosin. 25 The antioxidant effect of MRN-100 has been studied in several animal models and in in vitro studies, where it has been shown to protect against age-associated oxidative stress, 26 chemical carcinogens, 27 and oxidative stress–induced apoptosis in lymphocytes. 28 The findings of this study indicate that the natural product MRN-100 has the ability to activate human DCs and modify cytokine activity, including a significant increase in IL-10 expression.…”

Micronutrients: A Double-Edged Sword in Microbe-Induced Gastric Carcinogenesis

“…In contrast to the association between heme/iron and colorectal cancer, inverse relationships have been reported between iron content and esophageal and gastric cancer (Figure 1A, Key Figure) [8,19]. Experimental data from in vivo models have demonstrated that iron supplementation is protective against carcinogen-induced esophageal and gastric cancer [20], and, conversely, that iron deficiency accelerates carcinogen-induced gastrointestinal cancer and metastasis [17], results confirming the associations demonstrated in humans.…”