Background/Objectives: Diabetic cardiomyopathy (DCM) is a major cardiovascular complication of diabetes mellitus characterized by progressive myocardial remodeling driven by oxidative stress, inflammation, and fibrosis. The interleukin-33 (IL-33)/soluble suppression of tumorigenicity 2 (sST2) signaling axis has recently emerged as an important regulator of cardiac remodeling and a potential therapeutic target in DCM. N-acetylcysteine (NAC) and glycine exhibit complementary antioxidant and anti-inflammatory properties; however, their combined effects on circulating IL-33 and sST2 levels and myocardial structural remodeling in experimental diabetes remain insufficiently investigated. This study evaluated the effects of NAC and glycine, administered alone or in combination, on oxidative stress, inflammatory biomarkers, cardiac morphology, and serum sST2 levels in streptozotocin-induced diabetic rats. Methods: Thirty-four adult Wistar rats were randomly assigned to five groups: healthy controls, untreated diabetic animals, diabetic animals treated with NAC (100 mg/kg/day), glycine (250 mg/kg/day), or combined NAC and glycine for 12 weeks. Diabetes was induced by a single intraperitoneal injection of streptozotocin (55 mg/kg). Serum concentrations of sST2, IL-33, malondialdehyde (MDA), and superoxide dismutase (SOD) activity were determined. Cardiac remodeling was evaluated by stereological and histopathological analyses. Results: Experimental diabetes significantly increased serum sST2, IL-33, and MDA concentrations and induced marked myocardial remodeling characterized by expansion of the interstitial and perivascular compartments, increased connective tissue deposition, and reduced cardiomyocyte volume density. Both NAC and glycine significantly attenuated these biochemical and structural abnormalities compared with untreated diabetic animals. Treatment effects varied across outcomes. The combined NAC and glycine regimen was associated with particularly pronounced reductions in sST2 and IL-33 and with preservation of myocardial architecture, whereas the magnitude of improvement in oxidative stress markers differed between treatment groups. Conclusions: NAC and glycine, administered either alone or in combination, attenuated several biochemical and structural alterations associated with streptozotocin-induced diabetes. The magnitude of these effects varied across the assessed outcomes, with the combined regimen showing particularly favorable effects on circulating sST2 and IL-33 levels and myocardial structural remodeling, while some oxidative stress parameters showed greater improvement with NAC monotherapy. These outcome-dependent effects highlight the potential complementary actions of NAC and glycine without implying uniform superiority of the combined regimen. Overall, these findings provide an experimental basis for further investigation of NAC- and glycine-based therapeutic approaches for diabetes-associated myocardial remodeling.
Diabetic nephropathy (DN) is a major microvascular complication of diabetes mellitus and the leading cause of end‐stage renal disease. Oxidative stress and inflammation are central drivers of DN progression, yet no effective therapies exist to prevent or delay renal injury. This study investigated the renoprotective effects of glycine (GLY), N‐acetylcysteine (NAC), and their combination administered at early versus late stages of streptozotocin induced diabetes. Forty‐eight male Wistar rats (n = 48) were allocated into five groups: healthy controls (Group 1, n = 6), untreated diabetic rats (Group 2, n = 6), and three treatment groups (Groups 3–5, each n = 12). Diabetes was induced by a single intraperitoneal streptozotocin injection (55 mg/kg). Group 3 received NAC (100 mg/kg), Group 4 received GLY (250 mg/kg), and Group 5 received NAC + GLY. Each treatment group was subdivided into early (6 week, n = 6) and late (12 week, n = 6) intervention subgroups. Treatments were administered orally. Renal tissue was evaluated using classic histology, geometric morphometric analysis, and biochemical assays of superoxide dismutase (SOD) and myeloperoxidase (MPO). Statistical analyzes were performed using ANOVA with appropriate post hoc tests (p < 0.05). Untreated diabetic rats (Group 2) showed significantly decreased SOD activity, increased MPO levels, marked mesangial matrix expansion, glomerular hypercellularity, tubular epithelial degeneration, and interstitial inflammation with fibrosis. NAC (Group 3) and GLY (Group 4) each improved oxidative stress markers and partially restored glomerular and tubular morphology, with early treatment subgroups exhibiting more substantial benefit than late subgroups. The combined NAC + GLY therapy (Group 5) demonstrated the strongest renoprotective effect, preserving renal structure and biochemical parameters closest to healthy controls. To conclude, early combined administration of glycine and N‐acetylcysteine yields superior protection against diabetes‐induced renal injury compared with individual treatments. These findings support the therapeutic potential of antioxidant‐amino acid combinations in preventing or delaying diabetic nephropathy.
Background: Different dietary components can affect hematological and biochemical profiles, potentially causing pathohistological changes in liver and kidney tissue. Aim: The animals in the experiment consumed various bakery and meat products, and ultimately, the potential effects on hematological, biochemical, and pathological parameters were evaluated. Methods: The study involved 24 clinically healthy adult rats, randomized into three groups of eight rats each, as follows: rats that consumed meat products (group M), rats that consumed bakery products (group H), and a control group that consumed conventional rodent food (group K) for 7 weeks. After 7 weeks, hematological and biochemical blood analyses were conducted along with pathohistological examinations of the liver and kidneys. Results: Significant differences (p < 0.05) were observed among groups for several hematological and biochemical parameters, including creatinine (CREA), urea, blood urea nitrogen /CREA, calcium, alanine transaminase, alkaline phosphatase, and lipase. Consuming meat products had a less favorable impact on the occurrence of kidney function disorders. Group H exhibited significant differences in leukocyte and platelet counts compared with groups M and K. Extreme echinocytosis was recorded in group M, whereas sideropenic anemia was prominent in group H. Analysis of the livers of rats in groups K and H did not show significant differences in the observed parameters (gamma-glutamyl transferase and total bilirubin), whereas group M had a significantly higher degree of hepatocyte degeneration and steatosis, and the observed infiltrate was also more pronounced, but not significantly. The kidneys of group M showed discrete alterations of the microstructure, i.e., slightly increased cellularity of renal corpuscles and hypertrophy of proximal nephrocyte, whereas the kidney tissue of group K had a regular appearance. Conclusion: Consuming meat products was associated with adverse liver and kidney changes, whereas bakery products led to sideropenic anemia and altered hematological values.
The objective of this study was to confirm the effects of curcumin and to investigate the effects of its combination with a reduced dose (RD) of rosuvastatin in an adenine-induced model of chronic kidney disease (CKD) and associated dyslipidemia in rats. Renal function and morphology, as well as lipid status, were assessed using laboratory parameters and histopathological analysis. Male Wistar rats (n ═ 36) randomly divided into six groups, were treated for 24 days: normal control (standard diet), CKD control (adenine diet, 0.75% w/w adenine-supplemented diet), curcumin (100 mg/kg/day + adenine diet), rosuvastatin minimal therapeutic dose (MTD) (5 mg/day + adenine diet), rosuvastatin RD (25% of rosuvastatin MTD + adenine diet), and rosuvastatin RD + curcumin (25% of rosuvastatin MTD + curcumin 100 mg/kg/day + adenine diet) group. While rosuvastatin alone showed only antilipemic action, both curcumin alone and its combination with an RD of rosuvastatin showed better renal protection with lower serum creatinine levels and milder renal morphological alterations, as well as better antilipemic action with lower levels of triglycerides, very low-density lipoprotein, and low-density lipoprotein cholesterols compared with the levels in CKD control rats. Treatment with curcumin alone also resulted in a significantly higher estimated glomerular filtration rate, lower uric acid levels, and higher high-density lipoprotein cholesterol, while the combined therapy additionally resulted in higher serum albumin levels, lower total cholesterol, and both atherogenic and coronary risk indexes compared with CKD control rats. The results of this study confirmed the beneficial effects of curcumin alone and provided new evidence for the beneficial effects of its combination with an RD of rosuvastatin in rats with CKD and associated dyslipidemia.
Aim To determine the value of angles between the left coronary artery main trunk (LMT) and its branches, the anterior interventricular branch (LAD) and the circumflex branch (CX), and their possible relationship with the LMT length. Methods A total of 29 cadaveric hearts were used. The left coronary artery and its branches were dissected. The hearts were then classified according to the number of branches. The LMT length was measured with a digital gauge, and the LAD-CX angle, LMTLAD angle and LMT-CX angle with a manual goniometer. Results The average value of the LMT length was 9.0 mm (6.0-13.5). In 20 (68.97%) samples, the LMT was divided into two terminal branches. There was no statistically significant difference (p=0.321) in LMT length between the hearts with a bifurcation and without it. The average value of the LAD-CX angle was 89.0⁰ (74.5-93.0), with a statistically significant difference (p=0.020) comparing to hearts with trifurcation. The mean value of the LMT-LAD angle was 30.83±9.23⁰ and it was significantly lower (p=0.006) in the group of hearts with bifurcation compared to the group with trifurcation of the main trunk. Conclusion The LMT length shows great variability and is not related to the LAD-CX, LMT-LAD or the LMT-CX angle. Knowledge of the left coronary variation is essential in order to avoid misinterpretation of arteriogram.
Introduction: The human heart is in most cases vascularized by two coronary arteries, the right coronary artery (RCA) and the left coronary artery. The supernumerary coronary artery, which arises independently from the right aortic sinus and passes through sub-epicardial adipose tissue of the pulmonary conus and anterior side of the right ventricle is called the third coronary artery (TCA). Methods: This study consisted of 28 formalin-fixed adult human cadaveric hearts. The presence of the TCA was determined. The position of the orifice of the right and excess arteries in relation to the sinotubular junction was determined, and then also the position of the orifice of the excess arteries “on the o’clock level” in relation to the orifice of the RCA. The radius of these orifices and their distance from the orifice of the RCA were measured. The angle between the aorta and TCA, as well as RCA and conus branch, was measured. Results: A total 11 of specimens had supernumerary arteries. A supernumerary artery was found in two hearts. The angle formed by the aorta with the TCA was 60.09 ± 17.57, while the angle between the aorta and the conus branch had an average value of 89.88 ± 15.92. The orifices of all supernumerary arteries were located below the level of the sinotubular junction. The average diameter of the TCA was 1.49 mm ± 0.41. The average distance between the TCA orifice and the RCA orifice was 2.21 mm ± 1.03. In 45.45% cases, the orifice of TCA was located at the 10 o’clock level. Conclusion: The present study highlights the presence of the TCA. It may constitute a significant collateral circulation contributing to apical and septal perfusion. Interpretation of signs and symptoms of coronary occlusion should therefore include possible contribution of this vascular channel.
SUMMARY: Myocardial bridges are inborn anomalies frequently found in authopsies. Although tipically clinically silent, they are occasionally associated with severe clinical manifestations, e.g. myocardial ischemia or even sudden death. The pathophysiology and risk factors for these manifestations have not yet been completely elucidated. The connective tissue underneath the bridge has been considered as one of the factors the symptoms depend on. Thus, the aim of this research was to determine the histological characteristics of the connective tissue lying underneath the myocardial bridge and to contribute to a better understanding of the protective effects this passive compartment might have in prevention of severe clinical manifestations of myocardial bridging. The study was carried out on twenty hearts with myocardial bridges. Length of the bridge was determined using a precise electronic caliper. Sections of the myocardial bridges with the underlying connective tissue were obtained and prepared for qualitative and quantitative analysis. The connective tissue underneath the bridges was composed of adipose tissue and loose connective tissue in different ratios. The tissue underneath thin bridges was predominantly composed of adipose tissue, while loose connective tissue was the dominant component under thick bridges. The myocardial bridges had an average thickness of 0,98 ± 0.44 mm and an average length of 15,25±5,65 mm. We found a strong positive correlation between the myocardial bridge thickness and length (r = 0,860, p = 0,0001). The thickness of the passive connective tissue compartment under the myocardial bridges was 0,58±0,22 mm, and there was no correlation between this parameter and the myocardial bridge thickness (r = -0,011; p = 0,963). In the clinical evaluation of patients with these anomalies it is necessary to take into account independently the myocardial bridge thickness and length on one side and the thickness of the connective tissue lying underneath it on the other.
Background: Zearalenone is a widely spread mycotoxin, contaminant of most cereal grains. It has uterotropic, estrogenic and anabolic activity in farm animals. The results are hormonal disbalances as hyperestrogenism, Zearalenone inhibits follicle-stimulating hormone production, thus supressing ovarian follicle development and ovulation. Also, it induces oxidative stress. Melatonin acts as a potent natural antioxidant and regulates the reproductive function by modification of steroidogenesis. Objective: The present study was conducted to provide detailed qualitative histological analysis of uterus of female rats treated with zearalenone and melatonin and contribute to better understanding of the topic. Methods: Forty adult, female Wistar rats were equally divided into five groups: Z group – zearalenone, 0,3 mg/kg, i.g.; M group – melatonin, 10 mg/kg, i.p.; ZM group –concomitant application of zearalenone and melatonin in the same dosing regimen, VZ group–zearalenone vehiculum/sunflower oil, i.g. and MZ group–melatonin vehiculum/5% ethanol in Ringer, i.p. Animals were treated daily for 28 consecutive days. After that period, all animals were sacrificed to obtain samples for qualitative histological analysis using the light microscope. Results: Zearalenone led to the alterations of the uterine structures, predominantly in the endometrium that were characterized by metaplasia and hypertrophy of the epithelial cells and hypercellularity of the stroma. In the myometrium, zearalenone induced hypertrophy and hyperplasia of the myocytes. Conclusion: Melatonin, when applied together with zearalenone, blocked the adverse effects of the zearalenone.
The purpose of this study was to explore possible protective effects of vitamin D3 on serum glucose concentration, body weight and histopathology of pancreas and liver. Animals were divided into 3 groups: Control group (n=6), streptozotocin (STZ) group (n=6) and streptozotocin + vitamin D3 (STZ+D3) group (n=6). Rats in the STZ+D3 group starting from the 7th day of experiment were given vitamin D3 for 14 days. Glucose levels and body weight were measured on the 1, 7, 14 and 21st day of experiment. Qualitative histological analysis of pancreas and liver was done using the light microscope with a digital camera. Differences between the groups were tested by one-way analysis of variance (ANOVA) followed by Dunnett's posttest. Differences in repeated measures were tested using paired t-test. On day 14 and 21, blood glucose level in STZ+D3 group was significantly higher compared to the control group of animals but significantly lower than the glucose level registered in STZ group of rats. On day 14 and day 21, body weight in STZ rats was significantly lower compared to weight in STZ+D3 and control groups of rats. Morphological changes, such as shrinkage of islets, vacuolation of both endocrine and exocrine cells, were observed in pancreas of STZ group of animals but were nearly absent in STZ+D3 rats. Similarly, STZ+D3 group of rats showed preserved liver histoarchitecture. Obtained results suggest that vitamin D3 treatment reduces hyperglycemia, exerts beneficial effects on body weight and alleviates histopathological changes in pancreas and liver in STZ-induced diabetic rats.
Dinuclear ruthenium(II) Schiff base complex was selected for in vivo study among many other novel metal-based compounds, because of its previously proved in vitro anticancer and antibacterial properties. The aim was to investigate the potential toxicity of this compound in animal model through biochemical and histopathological assessment. Adult Swiss albino mice of both sexes were divided into high-dose and low-dose group that received a single intraperitoneal dose of ruthenium complex (175 mg/kg and 25 mg/kg, respectively) and one control group (vehicle only). After a follow-up period of 14 days, animals were sacrificed to obtain blood samples and organs. RESULTS: The test compound was well tolerated in a low-dose group and did not cause any mortality. The histological findings and serum biochemistry suggested a reversible character of alterations found in vital organs of this group. However, in the high-dose group, adverse effects were more severe and indicated dose and gender-related toxicity. Mild side effects found in a low-dose group together with excellent in vitro properties, made dinuclear ruthenium(II) Schiff base complex a promising candidate for further investigation and development as anticancer and antimicrobial agent (Tab. 4, Fig. 6, Ref. 32). Text in PDF www.elis.sk.
Breast cancer is one of the most common cancers in women in Bosnia and Herzegovina, and this is a serious public health problem. Since the use of dermatoglyphics has a long history of application in different scientific fields, the objective of this research was to find possible relation between the finger and palmar dermatoglyphic patterns and breast cancer risk in females with no breast cancer within the Bosnian-Herzegovinian population.
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