Summary
Colorectal cancer (CRC) ranks third in prevalence worldwide for both men and women. In recent years, nitric oxide (NO) and Hydrogen Sulfide (H2S) gas previously considered to be a potentially toxic chemical, has been established that have a role in cancer progression and prevention.
The present investigation included two sets of the experiments, in the First experiment set, which is case-control study was carried out at Rizgari Teaching Hospital and Nanakaly Hospital in Erbil City, blood sample from 40 colorectal cancer patient who were under chemotherapeutic treatment were obtained for serological tests including endocan, malondialdehyde (MDA) and electrolytes including K+, Na+ and Ca+2 estimation.
Non-significant change were observed in the level of serum endocan in CRC group (74.98 ± 7.315 pg/mL) as compared with healthy control (84.40 ± 4.518 pg/mL) and serum concentration in CRC patients group (3.939 ± 0.194 μmole/L) compared to healthy controls (3.44 ± 0.138 μmole/L). ROC curve analysis indicated that the endocan but not MDA can be used as a biomarker with predictive ability to discriminate patients with CRC.
Statistical analysis revealed that serum levels of Na+ (143.5±2.48 mEq /L), K+ (4.652±0.135 mEq/L) and Ca+2 (0.995±0.052 mEq/L) ions were non significantly changed in CRC patients compared to the healthy controls (139.7±0.91 mEq/L), (4.513 ± 0.146 mEq/L ) and (1.036 ± 0.026 mEq/L),
In the second experimental set, the study was concerned with the role of potassium (K+) channels in mediating relaxation of human mesenteric artery in response to nitric oxide (NO) donor “sodium nitroprusside (SNP)”and hydrogen sulfide (H2S) donor “sodium sulfide (Na2S). To do this, mesenteric arteries supplying blood flow to colorectal tumors were obtained during surgery and prepared for isometric tension recording in an organ bath, and isometric tension was recorded using PowerLab Data Acquisition System.
Separate sets of experiments were recorded. SNP and Na2S were added to norepinephrine (NE)-induced contraction during the peak value. Then maximal relaxation rates were calculated for four times at each 15 min intervals. Tetraethylammonium (TEA) Glibenclamide (GLIB), barium Chloride (BaCl2) and 4-aminopyredine (4-AP) were applied for investigating the molecular mechanism of the gasses. Preincubation of arterial rings for 20 minutes with individual TEA (1mM), GLIB (10-5M), BaCl2 (1mM) and 4-AP, (1mM) were significantly reduced relaxation caused by SNP and Na2S respectively.
While, in a separate set of experiments L-nitroarginine methyl ester (L-NAME, 3X10-4M) was used before applying Na2S and did not change the vasodilation induced by Na2S. Moreover, no change of mesenteric artery dilation was observed when SNP and Na2S were combined. On the other hand, preincubation of arterial rings with Propargylglycine (PAG, 10mM) significantly enhanced vasodilation induced by SNP.
These results indicate that no changes were observed in the serum endocan, MDA, K+, Na+ and Ca+2. K+ channels play a key role in the vasodilation of mesenteric arteries induced by NO and H2S. Finally, the activity of CSE enzyme supress the vasodilator ability of exogenous NO.
posted:12-3-2017