Abstract
The present work was undertaken to study the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on 1, 2-dimethyhydrazine (DMH) induced colon cancer and role of the cholinergic anti-inflammatory pathways (CAP) in the same. Groups of rats were randomly divided into ten groups (n = 8). DMH administration was very well apparent for autonomic dysfunction as observed through distorted hemodynamic (electrocardiogram and heart rate variability), increased aberrant crypt foci and flat neoplastic lesions (methylene blue staining, scanning electron microscopy and Hematoxylin and eosin staining). DMH administration was also recorded for per-oxidative damage. taVNS application restored the autonomic function, cellular morphology and curtailed the oxidative damage. DMH application conspicuously inhibited the mitochondrial apoptosis which was restored back after taVNS application, when scrutinized through immunoblotting and quantitative real time polymerase chain reaction studies. taVNS application up-regulated the CAP as perceived through increased expression for α7 nicotinic acetylcholine receptor(α7nAchR) and decreased expression for nuclear factor kappa-ligand-chain-enhancer of activated B cells (NFκBp65), tissue necrosis factor-α and high mobility group box-1 at protein and mRNA levels. All in all, taVNS up-surged the CAP to counteract DMH induced colon carcinogenesis. Among all the stimulation parameters used, taVNS 3 (pulse width-1 ms, frequency-6 Hz, voltage-6 v, duration-240 min) was observed to be the most effective. Since only chemotherapy and surgery are available options for management of CRC, which are troublesome and painful, there is currently no non-invasive method available for management of CRC. Results of the current study affirmed the effectiveness of taVNS against DMH induced colon cancer. The present study established taVNS as a novel and non-invasive approach toward the management of CRC.
Highlights
Cancer is an abnormal cell division, which begins from mucosal layer of colon and rectum and has the potential to invade adjacent tissues
Autonomic dysfunction is reported in most advanced cancers (Walsh and Nelson, 2002)
heart rate variability (HRV) is a functional biomarker of autonomic nervous system
Summary
Cancer is an abnormal cell division, which begins from mucosal layer of colon and rectum and has the potential to invade adjacent tissues. This is developed due to changeover of normal colonic epithelium to an adenomatous polyp and to invasive cancer. The genotypic expression of some fundamental properties in cell is necessary for carcinogenesis. These properties include: self-sufficiency in proliferation, insensitive nature to antigrowth, elusion to apoptosis, potency of unlimited replication, uninterrupted vascularization, invasion and metastasis (Hanahan and Weinberg, 2000). Numerous methods are applied for detection of CRC, including DNA stool test, sigmoidoscopy, colonoscopy, guaiac test, and immunochemical test of stool
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