Therapeutic effects of pentoxifylline on diabetic heart tissue via NOS

Abstract

Objective: Diabetes mellitus causes a decrease in cardiac output, arterial blood pressure, and heart rate. In this study, we aimed to investigate, at the molecular level, the effect of nitric oxide synthase (NOS) on heart pathology in type 1 diabetes and look at the therapeutic effect of pentoxifylline on this pathology.

Methods: In this experimental study, 50 Wistar albino male rats were used. The rats were divided into 5 groups: group C, control; group D, only diabetes; group D+PI and D+PII, diabetes + pentoxifylline; group P, only pentoxifylline. Group D+PI rats received 50 mg/kg/day pentoxifylline over two months. However, group D+PII rats received saline in the first month and 50 mg/kg/day of pentoxifylline over the following month. At the end of two months, NOS expressions in heart tissue were assessed through immunohistochemistry analysis. The data were compared by one-way ANOVA.

Results: At the end of the experiments, there was increased cytoplasmic vacuolization, myofibrillar loss, cytoplasmic eosinophilia, and degeneration of cardiomyocytes; nNOS and iNOS expressions in group D decreased compared with that in group C. In group D+PI and group D+PII, nNOS and iNOS expressions improved compared with group D.

Conclusion: As a result, we found that diabetes, a known chronic disease, causes serious damage in heart tissue. NOS plays a role in this damage, and pentoxifylline aided in improving nNOS and iNOS expression in this damage.

Figure 1

a–f. Light microscopy of heart tissue in different groups: (a) group C, normal heart architecture was observed; (b) group D, increased cytoplasmic vacuolization (thin arrow) and cytoplasmic eosinophilia of some cells (thick arrow) were exhibited; (c) group D, cytoplasmic vacuolization (thin arrow), cytoplasmic eosinophilia of some cells (thick arrow), and myofibrillar loss (red arrow) were particularly increased in the peripheral myocardium; (d) group D+PI, mild heart damage was observed; (e) group D+PII, normal heart architecture was observed; and (f) group P, normal heart architecture was observed. Hematoxylin & eosin

Figure 2

a-f. Immunohistochemical localization of neuronal, inducible, and endothelial NOS expression of the heart tissue and semiquantitative results of NOS content obtained by densitometric analysis of immunohistochemistry in different groups: (a) group C, (b) group D, (c) group D+PI, (d) group D+PII, (e) group P, and (f) negative controls. (Statistical analysis was used One-way ANOVA, posthoc Tukey test)

Figure 3

a-f. TUNEL staining of heart tissue in different groups: (a) group C, (b) group D, (c) group D+PI, (d) group D+PII, (e) group P, and (f) negative controls. TUNEL-positive cells (arrow) were observed in the heart. (Statistical analysis was used One-way ANOVA, posthoc Tukey test)