Bretschneider Solution and Two Antianginal Drugs Protect Peripheral Tissue in an Animal Model of Hemorrhagic Shock.

ABSTRACT: Shock and subsequent resuscitation provoke ischemia-reperfusion injury. Trimetazidine (TMZ), allopurinol (ALO), and histidine-tryptophan-ketoglutarate (HTK) solution, can protect from ischemia-reperfusion injury in chronic coronary syndromes and in transplantation. The objective of the current study is to compare, in a hemorrhagic shock and standard resuscitation animal model, organ damage parameters between placebo and treatment with TMZ, ALO, or HTK. Shock was induced in Wistar rats by controlled arterial bleeding, maintaining mean arterial pressure between 38 and 42 mm Hg for 60 minutes; then, drawn blood was reinfused. Animals were divided into: Sham (n = 4), Control (n = 6), TMZ (n = 7), ALO (n = 9), and HTK (n = 7). At the end of the experiment, animals were sacrificed and tissue harvested. TMZ, ALO and HTK decreased histopathologic damage in heart [Control: 1.72 (1.7-1.77); TMZ: 1.75 (1.72-1.79); ALO: 1.75 (1.74-1.8); HTK: 1.82 (1.78-1.85); all P < 0.05], kidney [Control: 3 (2-3); TMZ: 1 (1-2); ALO: 1 (1-1); HTK: 1(1-1); all P < 0.05] and intestine [Control: 3 (2-3); TMZ: 1 (1-2); ALO: 1 (1-1); HTK: 1 (0-2); all P < 0.05]. Also, treatment with TMZ, ALO, and HTK increased immunohistochemical expression of thioredoxin-1 in heart [Control: 6.6 (5.6-7.4); TMZ: 9.5 (8.1-9.7); ALO: 9.1 (8.4-10.2); HTK: 14.2 (12.6-15); all P < 0.05]; and kidney [Control: 4.6 (4-5.1); TMZ: 9.7 (9.3-9.9); ALO: 9.6 (9-9.9); HTK: 16.7 (16.1-17); all P < 0.05]. In an experimental model of hemorrhagic shock, TMZ, ALO, and HTK solution attenuated cell damage in multiple parenchyma and increased antioxidant defenses.

Metabolic disturbances and worsening of atherosclerotic lesions in ApoE-/- mice after cola beverages drinking.

BACKGROUND: Atherosclerosis is a major health burden. Metabolic disorders had been associated with large consumption of soft drinks. The rising incidence of atherosclerosis and metabolic alterations warrants the study of long-term soft drink consumption' effects on metabolism and atherosclerosis in genetic deficiency of apolipoprotein E which typically develops spontaneous atherosclerosis and metabolic alterations. METHODS: ApoE-/- mice were randomized in 3 groups accordingly with free access to: water (W), regular cola (C) or light cola (L). After 8 weeks, 50% of the animals in each group were euthanized ( TREATMENT: W8, C8, L8). The remaining mice (all groups) drank water for 8 weeks and were euthanized (Washout: W16, C16, L16). Body weight and food and drink consumption were periodically measured. Blood was collected (biochemistry). At autopsy, transverse aortic sinus sections were serially cut and stained (histomorphometry); livers and kidneys were processed (microscopy). MANOVA (identification of variance factors) was followed by ANOVA and LSD tests (within-factor differences between levels). Conventionally a p< 0.05 was considered significant. RESULTS: TREATMENT increased drinking volumes (vs W8: 4 fold C8, p<0.0001; +47% L8, p<0.02). Only C reduced eating amounts (-54%, p<0.05 vs W8). I). Compared with W8: C8 developed hyperglycemia (+43%, p<0.03) and increased non-HDL cholesterol (+54%, p<0.05); L8 showed decreased glycemia (-15%, p<0.05 vs W8) and increased creatinine (2.5 fold, p<0.04), urea (+74, p<0.03) and aspartate-aminotransferase (2.8 fold, p<0.05). Hypercreatininemia was observed in L16 (2.7 fold vs W16, p<0.05). Hypertriglyceridemia (+91%, p<0.008) and hyperuremia (+68%, p<0.03) developed over time of study (age). II). TREATMENT caused plaque area increase (vs W8: 28% C8, p<0.02 and 50% L8, p<0.01; vs W16: 43% C16, p<0.05 and 68% L16, p<0.02) and stenosis (vs W8: 38% C8, p<0.04 and 57% L8, p<0.01; vs W16: 71% C16, p<0.01 and 46% L16, p<0.04). Age also caused plaque area increase (56%, p<0.04). TREATMENT- and age-effects on plaque enlargement were additive. CONCLUSION: Cola beverages caused atherosclerotic lesions' enlargement with metabolic (C) or non metabolic disturbances (L). ApoE-/- mice were particularly sensitive to L treatment. These findings may likely relate to caramel colorant and non-nutritive sweeteners in cola drinks and have potential implications in particularly sensitive individuals.

Structural changes in endocrine pancreas of male Wistar rats due to chronic cola drink consumption. Role of PDX-1.

AIM: The objective of this work was to analyze the structural changes of the pancreatic islets in rats, after 6 month consuming regular and light cola for 6 months. Also, we have analyzed the possible role of PDX-1 in that process. Finally, with the available knowledge, we propose a general working hypothesis that explains the succession of phenomena observed. Previously, we reported evidence showing that chronic cola consumption in rats impairs pancreatic metabolism of insulin and glucagon and produces some alterations typically observed in the metabolic syndrome, with an increase in oxidative stress. Of note It is worth mentioning that no apoptosis nor proliferation of islet cells could be demonstrated. In the present study, 36 male Wistar rats were divided into three groups to and given free access to freely drink regular cola (C), light cola (L), or water (W, control). We assessed the impact of the three different beverages in on glucose tolerance, lipid levels, creatinine levels and immunohistochemical changes addressed for the expression of insulin, glucagon, PDX-1 and NGN3 in islet cells, to evaluate the possible participation of PDX-1 in the changes observed in α and ß cells after 6 months of treatment. Moreover, we assessed by stereological methods, the mean volume of islets (Vi) and three important variables: the fractional ß -cell area, the cross-sectional area of alpha (A α-cell) and beta cells (A ß-cell), and the number of ß and α cell per body weight. Data were analyzed by two-way ANOVA followed by Bonferroni's multiple t-test or by Kruskal-Wallis test, then followed by Dunn's test (depending on distribution). Statistical significance was set at p<0.05. Cola drinking caused impaired glucose tolerance as well as fasting hyperglycemia (mean:148; CI:137-153; p<0.05 vs W) and an increase of in insulin immunolabeling (27.3±19.7; p<0.05 vs W and L). Immunohistochemical expression for PDX-1 was significantly high in C group compared to W (0.79±0.71; p<0.05). In this case, we observed cytoplasmatic and nuclear localization. Likewise, a mild but significant decrease of in Vi was detected after 6 months in C compared to W group (8.2±2.5; p<0.05). Also, we observed a significant decrease of in the fractional ß cell area (78.2±30.9; p<0.05) compared to W. Accordingly, a reduced mean value of islet α and ß cell number per body weight (0.05±0.02 and 0.08±0.04 respectively; both p<0.05) compared to W was detected. Interestingly, consumption of light cola increased the Vi (10.7±3.6; p<0.05) compared to W. In line with this, a decreased cross-sectional area of ß-cells was observed after chronic consumption of both, regular (78.2±30.9; p<0.05) and light cola (110.5±24.3; p<0.05), compared to W. As for, NGN3, it was negative in all three groups. Our results support the idea that PDX-1 plays a key role in the dynamics of the pancreatic islets after chronic consumption of sweetened beverages. In this experimental model, the loss of islets cells might be attributed to autophagy, favored by the local metabolic conditions and oxidative stress.