Inhibition of azoxymethane‐induced experimental colon carcinogenesis in wistar rats by 6‐hydroxydopamine

Abstract

The effects of 6-hydroxydopamine (6-OHDA) on the incidence, number and histology of colon tumors induced by azoxymethane (AOM), and on norepinephrine (NE) concentration in the colon wall and the labelling index of the colon mucosa were investigated in Wistar rats. Rats received sub-cutaneous (s.c.) injections of AOM once a week for 10 weeks, and throughout 35 weeks were also given intraperitoneal (i.p.) injections of 6-OHDA. Prolonged administration of 6-OHDA was found to cause a significant reduction in the incidence and number of colon tumors. However, it had no influence on the histological features or depths of involvement of colon tumors and/or adenocarcinomas. Its administration also caused significant decreases in the NE concentration in the colon wall and in the labelling index of the colon mucosa. Our findings indicate that 6-OHDA has a protective effect against colon carcinogenesis, and that the activity of the sympathetic nervous system may have an important influence on colon carcinogenesis.

Is norepinephrine an etiological factor in some types of cancer?

“…9 I now describe in greater detail the aforementioned 7 lines of evidence that support an etiological role for NE in some types of cancer. The first line of evidence has been put forth primarily by a group of researchers in Japan during the last several decades, [11][12][13][14][15][16][17][18][19][20] as well as by some Russian scientists [21][22][23] and others. 24,25 This line indicates that in rodents the level of NE, or degree of activation of adrenoceptors with drugs, in certain bodily tissues correlates with the degree of tumorigenesis in those tissues.…”

“…24,25 This line indicates that in rodents the level of NE, or degree of activation of adrenoceptors with drugs, in certain bodily tissues correlates with the degree of tumorigenesis in those tissues. In particular, during chemically induced carcinogenesis, when the level of NE is increased with drugs such as bombesin 11,12 or the tricyclic antidepressant desipramine, 13 or a low protein diet, 14,15 tumorigenesis increases; when the level of NE is decreased with 6-hydroxydopamine, 16 phenylalanine, 17 or cysteamine, 18,19 tumorigenesis decreases. However, when the level of NE is decreased with clonidine, tumorigenesis is unaffected.…”

“…20 These studies focused on the gastrointestinal (GI) tract, but also studied other organ system components such as the liver. 18 In most of these studies, tumorigenesis was induced by the carcinogens N-methyl-N 0 -nitro-N-nitrosoguanidine 11,14,17,20 and azoxymethane, 12,13,15,16,19 which increase the baseline number of tumors, and the various drug and other treatments were tested for modulation of this baseline number. Testing for modulation of tumorigenesis without using chemical carcinogens is not feasible due to the extremely large sample size of animals that would be necessary since the number of tumors would be quite low.…”

Effect of Mirtazapine on MNNG-Induced Gastric Adenocarcinoma in Rats

“…depression associated with psychosomatic and somatic symptoms was seen in majority of patients with GIS diseases (Guldahl, 1977). Tatsuta et al (1989) reported that supression of sympathetic nervous system inhibits carcinogenesis while stimulation of sympathetic nervous system activity increases carcinogenesis (Tatsuta et al, 1989;1992). It's well known that main mechanism of action of antidepressant agents is oriented to increase noradrenergic, serotonergic and dopaminergic activity (Baldessarini, 2005).…”

Occurrence of anticancer activity of prednisolone via adrenalectomy and inhibition of adrenaline in rats

“…10 Previous findings indicate that increased sympathetic nervous system activity enhances the development of gastric cancers, and suppression of sympathetic nervous system activity inhibits carcinogenesis. 11,12 The role of catecholamines are important in different cancer types because of their regulatory effects on tumor angiogenesis, [13][14][15][16] which is critical for the growth and progression of malignant tumors. 17 Bromocriptine is a dopamine receptor agonist known to enhance gastric carcinogenesis induced by Nmethyl-N 0 -nitro-N-nitrosoguanidine (MNNG) in Wistar rats.…”