Study of left ventricular myocardial hypertrophy in rats with experimental type 2 diabetes and following administration of L-arginine and N-acetyl-L-cysteine

Abstract

Aim. To evaluate the morphometric parameters of left ventricular myocardial hypertrophy in rats with experimental type 2 diabetes mellitus (DM2) and with L-arginine and N-acetyl-L-cysteine administration.

Materials and methods. The study was conducted on 42 male Wistar rats. DM2 was modeled by an 8-week high-fat diet followed by the administration of streptozotocin (30 mg/kg). The animals were divided into a control group and three DM2subgroups: without amino acids, with L-arginine administration and with N-acetyl-L-cysteine administration for 2 weeks dissolved in drinking water (1.5 g/kg/l). Histological staining with hematoxylin and eosin was performed. Morphometrically, the mean area and minimum Feret diameter of cardiomyocytes (CMC), total CMC area, mean and total nuclear area were assessed using ImageJ with subsequent calculation of the nuclear-cytoplasmic ratio (NCR) and cell density per 1 mm² of the tissue.

Results. The development of DM2 led to pronounced hypertrophy: the mean area of CMC increased by 28 %, and minimum Feret diameter by 23 % compared to the control. An increase in mean nuclear area of 29 % was observed, alongside a decrease in NCR by 12 % and cell density by 15 %. Administration of L-arginine to DM2 animals contributed to a decrease in mean CMC area by 8 % and restoration of cell density by 18 % compared to the non-supplemented DM2 group. N-acetyl-L-cysteine demonstrated a more pronounced effect compared to L-arginine, with statistically significant reductions in mean nuclear area (14 %) and increases in CMC cytoplasmic area (4 %) and cell density (12 %), p ˂ 0.05.

Conclusions. The development of experimental type 2 diabetes mellitus leads to pronounced hypertrophic structural reorganization of the left ventricular myocardium with impairment of the nuclear-to-cytoplasmic ratio and reduced cardiomyocyte density. Administration of L-arginine exerts a cardioprotective effect, manifested by attenuation of diabetes-induced hypertrophic remodeling, reduction of the nuclear-to-cytoplasmic ratio, and increased cell density per 1 mm² of the tissue. Administration of N-acetyl-L-cysteine demonstrates a more pronounced effect compared to L-arginine, optimizing the balance between the nuclear and cytoplasmic compartments of the myocardial parenchyma, successfully restoring histological cell density per 1 mm² of the tissue.