Protective effect of metformin in an aberrant crypt foci model induced by 1,2‐dimethylhydrazine: Modulation of oxidative stress and inflammatory process

Abstract

Colorectal Cancer (CRC) is the third most frequent type of cancer worldwide. In the past few years, studies have revealed a protective effect of metformin (MET-an anti-hyperglycemic drug, used to treat type 2 diabetes), against CRC. The protective effect of MET has been associated with AMPK activation (and mTOR inhibition), resulting in suppressed protein synthesis, and reduced cell proliferation in malignant transformed cells. To elucidate new mechanisms for the protective effect of metformin, we evaluated the oxidative stress and inflammatory process modulation, since these processes are strictly involved in colorectal carcinogenesis. The present study evaluated the protective effect of MET in a CRC model induced by 1,2-dimethylhydrazine (DMH) in Balb/c female mice. The simultaneous/continuous treatment (administration of MET and DMH simultaneously), revealed protective activity of MET, preventing the formation of aberrant crypt foci (ACF) in 71.4% at distal colon sections, and was able to restore basal labeling of apoptosis. Treatment with MET also reduced the inflammatory process induced by DMH, resulting in of the reduction of oxidative stress and nitric oxide related parameters. © 2016 Wiley Periodicals, Inc.

Antipleuritic and Vascular Permeability Inhibition of the Ethyl Acetate-Petroleum Ether Stem Bark Extract ofMaerua angolensisDC (Capparaceae) in Murine

“…Schreck et al [ 44 ] demonstrated that antioxidants inhibit nuclear factor kappa light-chain-enhancer of activated B cells (NF-kB), whereas ROS activate NF- κ B, a transcription factor which activates the transcription of several genes involved in inflammation [ 45 , 46 ]. The protective role of GSH against inflammatory diseases has been proven by depleting endogenous GSH with Buthionine sulfoximine (BSO) [ 47 , 48 ] which resulted in aggravating effect on various models of inflammation including carrageenan induced pleurisy. CAT which is localized in subcellular organelles of peroxisomes catalyses the conversion of hydrogen peroxide to water and oxygen [ 49 ]; SOD in cells work in conjunction with H 2 O 2 -removing enzymes such as glutathione peroxidase (GPx) or CAT to prevent action of H 2 O 2 , which in turn inhibits the formation of hydroxyl radicals [ 50 , 51 ].…”

The Complex Puzzle of Interactions Among Functional Food, Gut Microbiota, and Colorectal Cancer

“…The former is characterized by a surgical process, radiation therapy and ablation, while the latter is targeted chemotherapy ( 29 , 30 , 32 ). CRC presents high frequency ( 1 , 30 , 33 ). For Arnold et al ( 34 ), the number of new cases of this neoplasm will increase by 60% by the year 2030, representing 2.2 million affected and 1.1 million deaths.…”

“…Colorectal carcinogenesis (CRC) is a neoplastic modality with a wide and varied incidence and geographical distribution ( 1 ). CRC dissemination can be observed from the alarming epidemiological panorama, and future estimates demonstrate a considerable increase in the number of new cases of and deaths from CRC ( 2 ).…”

Metformin and Colorectal Cancer – A Systematic Review.

“…Suppression of colonic mucosal proliferation is achieved by a decrease in levels of proteins important in cell proliferation (including decreased levels of phosphorylated mTOR, S6 kinase, and S6 protein) through AMPK activation [34]. In the study by Bordini et al metformin had protective properties by preventing the formation of aberrant crypt foci (ACF) and inflammatory process induced by 1,2-dimethylhydrazine (DMH) in mice [35]. In a study on rats the DMH-induced tumor formation (tumor differentiation, invasion depth) was dose dependently inhibited by metformin administration [36].…”