Empagliflozin and sacubitril/valsartan reverse methotrexate cardiotoxicity by repressing oxidative stress and hypoxia in heart embryonic H9c2 cardiomyocytes - the role of morphology of mitochondria observed on electron microscopy.

OBJECTIVE: Oxidative stress and hypoxia play an important role in the pathogenesis of various cardiovascular diseases. We aimed to evaluate the effectiveness of sacubitril/valsartan (S/V) and Empagliflozin (EMPA) on hypoxia-inducible factor-1α (HIF-1α) and oxidative stress in H9c2 rat embryonic cardiomyocyte cells. MATERIALS AND METHODS: BH9c2 cardiomyocyte cells were treated with methotrexate (MTX) (10-0.156 µM), empagliflozin (EMPA; 10-0.153 µM) and sacubitril/valsartan (S/V; 100-1.062 µM) for 24, 48 and 72 h. The half maximum inhibitory concentration (IC50) and half maximum excitation concentration (EC50) values of MTX, EMPA and S/V were determined. The cells under investigation were exposed to 2.2 µM MTX before treatment with 2 µM EMPA and 25 µM S/V. The cell viability, lipid peroxidation, oxidation of proteins and antioxidant parameters were measured while morphological changes were also observed by transmission electron microscopy (TEM). RESULTS: The results showed that treatment with 2 µM EMPA, 25 µM S/V or their combination produced a protective effect against the reduction in cell viability caused by 2.2 µM MTX.  While HIF-1α levels plunged to their lowest with S/V treatment, oxidant parameters dipped, and antioxidant parameters soared to their highest level with S/V and EMPA combination treatment. A negative correlation was found between HIF-1α and total antioxidant capacity in the S/V treatment group. CONCLUSIONS: A significant decrease in HIF-1α and oxidant molecules together with an enhancement in antioxidant molecules and normalization of the mitochondria morphology as observed on electron microscopy in S/V and EMPA-treated cells were detected. Although S/V and EMPA have both protective effects against cardiac ischemia and oxidative damage, this effect may be increased more with S/V treatment alone compared to combined treatment.

Evaluation of the distribution of mechanoreceptors in the hip joint with severe coxarthrosis in 9 patients: A histologic and stereological study.

Due to its high mobility, hip joint plays a crucial role in executing many movements such as standing, sitting, running, crouching. The distribution of mechanoreceptors and neural elements in anatomical structures that provide stabilization of the hip joint is important in determining the optimal surgical incision site for the hip joint stabilizers in patients with coxarthrosis. Various studies have been conducted about the mechanoreceptors and distribution of neural elements in structures such as the transvers acetabular ligament, teres (round) ligament of femur, acetabular labrum and hip joint capsule with using various staining methods. To our knowledge, there is insufficient information about the mechanoreceptor distribution within the anatomic structures that participate in stabilization of the hip joint. This study is planned to examine the distribution of mechanoreceptors in the transverse acetabular ligament, teres ligament, acetabular labrum and joint capsule in samples obtained during the surgery who are operated for hip replacement surgery due to severe coxarthrosis. Each specimen was stained with silver impregnation technique and density of mechanoreceptors were estimated by stereological method. Teres ligament has the highest number of mechanoreceptors among all other specimens. Within the joint capsule, mechanoreceptors were most abundant at its antero-inferior part, whereas its anterior part contained the lowest number of mechanoreceptors. These results suggest that, as the anterior part of hip capsule bears the lowest number of mechanoreceptors, it might be safer for incision during total hip arthroplasty surgery.