The influence of septal lesions on sodium and water retention induced by Walker 256 tumor

Abstract

In the course of studies on the effects of septal area lesions on neuroimmunomodulation and Walker 256 tumor development, it was observed that tumor-induced sodium and water retention was less marked in lesioned than in non-lesioned rats. In the present study possible mechanisms involved in this phenomenon were investigated. The experiments were performed in septal-lesioned (LW; N = 15) and sham-operated (SW; N = 7) 8-week-old male Wistar rats, which received multifocal simultaneous subcutaneous (sc) inoculations of Walker 256 tumor cells about 30 days after the stereotaxic surgery. Control groups (no tumor, sham-operated food-restricted (SFR), N = 7) and lesioned food-restricted (LFR, N = 10) were subjected to a feeding pattern similar to that observed in tumor-bearing animals. Multifocal inoculation of Walker 256 tumor rapidly induces anorexia, which is paradoxically accompanied by an increase in body weight, as a result of renal Na + and fluid retention. These effects of the tumor were also seen in LW rats, although the rise in fractional sodium balance during the early clinical period was significantly smaller than in SW rats (day 4: SW = 47.6 ± 6.4% and LW = 13.8 ± 5.2%; day 5: SW = 57.5 ± 3.5% and LW = 25.7 ± 4.8%; day 6: SW = 54.4 ± 3.8% and LW = 32.1 ± 4.4%; P<0.05), suggesting a temporary reduction in tumor-induced sodium retention. In contrast, urine output was significantly reduced in SW rats and increased in LW rats and SW up to 4.5 ml/100 g body weight), with no change in osmolar excretion. These temporary changes in the tumors effects on LW rats may reflect a reversal of the secondary central antidiuretic response induced by the tumor (from antidiuretic to diuretic).

The hemolytic component of cancer anemia: effects of osmotic and metabolic stress on the erythrocytes of rats bearing multifocal inoculations of the Walker 256 tumor

“…The effects began 3-4 days after inoculation and progressed rapidly thereafter, and would have resulted in death 8-9 days later (7,8) if the rats had not been sacrificed at fixed times according to the experimental protocol. The effects developed in the absence of complications such as bleeding, invasions or visible metastases, as confirmed at autopsy.…”

“…A further improvement in the handling of this problem was described by Rettori et al (7). The multifocal tumor model avoids all of these problems by synchronizing the onset and progress of the systemic effects of the final stage of cancer among the individuals of the experimental group (7,8). Under the latter conditions, the hemolytic component of cancer anemia is of particular importance as described for humans by Hyman and Harvey in the early 50s (4).…”

“…However, if instead of the usual unifocal tumor growth model, the studies are initiated using multifocal simultaneous tumor inoculations (simulating the metastatic dissemination of the final stage), the systemic effects of cancer, including anemia, appear rapidly and synchronously in all animals (7,8). The development of anemia under these conditions is similar to that found in terminal cancer patients, in which the rate of RBC destruction is very high (4,9).…”

Tumor growth characteristics of the Walker 256 AR tumor, a regressive variant of the rat Walker 256 A tumor

“…The Walker 256 (W256) tumor has been extensively used in the studies of cancer pathophysiology, tumor cell metabolism and immune response (Toal et al, 1960;Morrison, 1971;Rettori et al, 1995;Guimarães et al, 1999;Buffon et al, Degasperi et al, 2006;Perroud et al, 2006). Two variants of this tumor have been previously reported as W256 A and B (Guaitani et al, 1982), which are currently known by their growth capacity and lethality after subcutaneous (sc) injection in Wistar rats.…”

“…Two variants of this tumor have been previously reported as W256 A and B (Guaitani et al, 1982), which are currently known by their growth capacity and lethality after subcutaneous (sc) injection in Wistar rats. This lethality is associated to the severe homeostatic disturbances induced by the W256 tumor, which includes anorexia (Rettori et al, 1995;Guaitani et al, 1982), anemia (Zucker et al, 1977;Vido et al, 2000), thymus atrophy (Rettori et al, 1995) and hydro electrolyte disturbances with glomerular filtration and tubular function alterations (Toal et al, 1960;Morrison, 1971;Rettori et al, 1995;Guimarães et al, 1999;Rettori et al, 2000). Nevertheless, spontaneous W256 tumor regression can occur.…”