Roflumilast counteracts DMH-induced preneoplastic colon damage in albino Wistar rats

Abstract

Objective: The study explored the chemoprophylactic potential of roflumilast against 1,2-dimethylhydrazine (DMH) actuated preneoplastic colon damage in albino Wistar rats. Methods: Animals were arbitrarily divided into five groups of six animals each. DMH was used to induce preneoplastic colon damage (20 mg/kg/7 days, subcutaneously, for 42 days). Roflumilast was administered subcutaneously at two doses (1 and 5 mg/kg/day, from day 28 to 42). At the end of the study, the animals were recorded for the electrocardiographic changes and heart rate variability (HRV) paradigms on 42nd day, using PowerLab system. Blood samples were collected from all the animals to measure hydrogen sulfide (H2S) and nitric acid. The colon tissue was dissected out and analyzed for inflammatory markers, biochemical parameters including, superoxide dismutase, thiobarbituric acid reactive substances, catalase, and glutathione reductase and histopathology. Results: DMH caused derangement of HRV factors, abnormal antioxidant markers, and elevated levels of inflammatory markers. H2S and nitric oxide levels upsurge in DMH-treated rats and promoted preneoplastic damage. Histopathologically, loss of crypts, goblet cells, and distorted lamina propria were observed in toxic group. Treatment with roflumilast was able to curtail down oxidative stress and inflammatory markers and stabilitate the hemodynamic derangements as well as was able to restore the normal architecture of colonic mucosa. Conclusion: The findings from the present study conclude that treatment with roflumilast positively modulates the preneoplastic colon damage.

AUT-M enterosorbent stabilizes glutathione system in vincristine-treated rats with dimethylhydrazine-induced colon cancer

“…However, the action mechanism of this cytostatic is associated with a number of side effects. In particular, the formation of free radicals, the development of oxidative stress, increased endogenous intoxication and toxic cell damage [25][26][27]. However, we found that the administration of Vincristine to rats with DMHinduced carcinogenesis after 21 days of enterosorption with AUTM sorbent has little effect on the state of the glutathione system.…”

Amelioration of N,N′-dimethylhydrazine induced colon toxicity by epigallocatechin gallate in Wistar rats

“…59 It is well known that DMH toxicity causes the destruction of goblet cells which leads to colon damage. 60 Goblet cells named due to their cup-like looks, packed with mucin in the cytoplasm have specialized in the production and secretion of mucus. 61 Mucus is gel-like secretion mostly formed of water and mucin, a high molecular weight glycosylated protein that forms a protective layer in the intestine.…”

Putative role of non‐invasive vagus nerve stimulation in cancer pathology and immunotherapy: Can this be a hidden treasure, especially for the elderly?

“…Consequently, non‐invasive VNS has been reported to surge CAP to suppress 1, 2‐dimethyhydrazine (DMH) induced colon cancinogenesis 99 . This role is similar to that of the drug, Roflumilast, a selective phosphodiesterase‐4 inhibitor (PDE4) 100 . Furthermore, non‐invasive VNS stimulates tumor‐infiltrating lymphocytes 72 .…”

“… 99 This role is similar to that of the drug, Roflumilast, a selective phosphodiesterase‐4 inhibitor (PDE4). 100 Furthermore, non‐invasive VNS stimulates tumor‐infiltrating lymphocytes. 72 The tumor‐infiltrating lymphocytes are types of immune cells that help attenuate acute inflammatory response and kill cancer cells.…”