Objective: This study aimed to evaluate the protective effects of bosentan, a dual endothelin receptor antagonist, against skeletal muscle ischemia-reperfusion injury (IRI) in rats. Methods: A total of 24 male Wistar Albino rats were divided into four groups: control (C, n=6), bosentan-treated (B, n=6), ischemia-reperfusion (IR, n=6), and bosentan plus ischemia-reperfusion (B+IR, n=6). Bosentan (10 mg/kg) was administered 30 minutes prior to reperfusion. In the IR and B+IR groups, ischemia was induced using vascular bulldog clamps for 45 minutes, followed by 120 minutes of reperfusion. Results: Histological and biochemical assessments revealed significant differences among the groups. The disorganization and degeneration scores of the muscle cells in the B+IR group were significantly lower than those in the IR group (P = 0.001). The degree of interstitial edema in the IR group was markedly more severe than in the C and B groups (all P < 0.001), while the interstitial edema score in the B+IR group was significantly lower than that in the IR group (P < 0.001). The total muscle injury scores were markedly reduced in the B+IR group compared to the IR group (P < 0.001). Biochemically, TAS levels were significantly higher in the B+IR group compared to the IR group (1.03 ± 0.18 vs 0.59 ± 0.10 mmol/L, P = 0.016). Conversely, TOS (1.97 ± 0.39 vs 2.86 ± 0.43 IU/mg, P < 0.001) and OSI levels (P < 0.001) were significantly lower in the B+IR group. Additionally, paraoxonase (PON-1) enzyme activity was significantly reduced in the B+IR group compared to the IR group (P < 0.001). These findings suggest that bosentan exerts its protective effects by antagonizing endothelin-1 receptors, thereby mitigating vasoconstriction, oxidative stress, and inflammation. The observed reductions in muscle cell disorganization, interstitial edema, hemorrhage, neutrophil infiltration and oxidative stress markers underscore bosentan’s potential as a therapeutic agent for managing ischemia-reperfusion injury. Conclusion: Bosentan demonstrates significant protective effects against skeletal muscle IRI by reducing oxidative stress and inflammation through endothelin receptor antagonism. These findings underscore bosentan’s potential as a therapeutic agent for mitigating ischemia-reperfusion injury in vascular surgeries and managing critical limb ischemia in clinical settings. Further research is warranted to explore the long-term effects of bosentan on muscle recovery and systemic health following ischemia-reperfusion injury.

Background and Objectives: Hind limb ischemia–reperfusion (I/R) injury is a serious clinical condition that requires urgent treatment and develops as a result of a sudden decrease in blood flow in the extremity. Antioxidant combinations are frequently used in diseases today. This study aimed to investigate and compare the effectiveness of ellagic acid (EA) and berberine (BER), which are important antioxidants, and the combination on hind limb I/R injury to evaluate their therapeutic power. Materials and Methods: Thirty-five male Sprague Dawley rats were randomly divided into five groups: sham, I/R, EA+I/R, BER+I/R, and EA/BER+I/R. In the I/R procedure, the infrarenal abdominal aorta was clamped and reperfused for 2 h. EA (100 mg/kg, ip) and BER (200 mg/kg, ip) were administered in the 75th minute of ischemia. Oxidative stress markers (MDA, GSH, SOD, and CAT) and TNF-α were measured. Apoptosis (Bax, Bcl-2, and Cleaved caspase-3) and pyroptosis (Nrf2, NLRP3, and Gasdermin D) pathways were evaluated via Western blot. Muscle tissue was examined histopathologically by hematoxylin eosin staining. One-way ANOVA and post hoc LSD tests were applied for statistical analyses (p < 0.05). Results: Bax levels increased in the ischemia group and decreased with EA and BER (p < 0.05). Bcl-2 levels decreased in the ischemia group but increased with EA and BER (p < 0.05). The highest level of the Bax/Bcl-2 ratio was in the I/R group (p < 0.05). Cleaved caspase 3 was higher in the other groups compared to the sham group (p < 0.05). While Nrf2 decreased in the I/R group, NLRP3 and Gasdermin D increased; EA and BER normalized these levels (p < 0.05). In the histopathological analysis, a combination of EA and BER reduced damage (p < 0.05). TNF-α levels were similar between groups (p > 0.05). MDA levels were reduced by EA and BER, but GSH, SOD, and CAT levels were increased (p < 0.05). Conclusions: It was concluded that TNF-α levels depend on the degree and duration of inflammation and that no difference was found in relation to duration in this study. As a result, EA, BER, and their combination could be potential treatment agents on hind limb I/R injury with these positive effects.

Stereotactic surgery is a technique that can be used to locate small targets in the body and administer interventions and/or treatments, such as injections, to the specific target. Stereotactic surgery is frequently used to create neurological disease models in experimental research in addition to clinical practice. The injection is administered with appropriate glass injectors using the rodent brain coordinate atlas after the specific brain region is determined. Alzheimer’s disease (AD), the most common cause of dementia, has no curative treatment yet. AD models can be created in rodents through stereotactic surgery and injections of different substances. These AD models represent the disease and are frequently used especially for drug development studies. AD-like models seem to examine different and unidirectional developmental mechanisms according to the creating way. However, AD is a multidirectional disease. AD rodent models created using different methods have specific properties. This review aims to explain the basic aspects of stereotactic surgery and to discuss AD rodent models created with this surgical technique and also with alternate methods.

Aim: Alzheimer's disease is a neurodegenerative disease with cognitive loss, which does not have a curative treatment and a bloodbased biomarker to make a definitive diagnosis. There is a strong relationship between Alzheimer's disease and type 2 diabetes mellitus. Neutrophil-lymphocyte, platelet-lymphocyte and monocyte-lymphocyte ratios are recommended parameters as inflammation markers. It was aimed to compare blood parameters and their ratios to each other in terms of their potential to provide early diagnosis in patients with Alzheimer's disease and type 2 diabetes mellitus. Material and Methods: 80 healthy controls, 47 type 2 diabetes mellitus and 45 Alzheimer's type dementia patients were included in this study. Various blood parameters and their ratios to each other were scanned. One way ANOVA and post hoc Scheffe tests were used for statistical analysis. Results: Serum iron levels were lower in type 2 diabetes mellitus (53.21±29.28 μg/dL) and Alzheimer’s disease (61.26±21.69 μg/dL) groups compared to the control (76.96±30.99 μg/dL) (p=0.001). Lymphocyte numbers were lower in type 2 diabetes mellitus (1.94±0.79 count.10³) and Alzheimer’s disease (1.84±0.68 count.10³) groups compared to the control (2.25±1.03 count.10³) (p=0.032). Monocytelymphocyte ratio were significantly higher in type 2 diabetes mellitus (0.3±0.18) and Alzheimer’s disease (0.28±0.11) groups compared to the control (0.24±0.1) (p=0.039). Conclusion: The high monocyte-lymphocyte ratio can be considered as an indicator of systemic inflammation in Alzheimer's disease and type 2 diabetes mellitus. In conclusion, serum iron levels, lymphocyte numbers and monocyte-lymphocyte ratio as inflammation markers can be useful for the early diagnosis of type 2 diabetes mellitus and Alzheimer’s disease