Fingolimod (FTY720) inhibits Ca<sup>2+</sup>-permeable, Mg<sup>2+</sup>-sensitive channels called transient receptor potential melastatin 7 (TRPM7), but its effects on Ca<sup>2+</sup> paradox (CP)-induced myocardial damage have not been evaluated. We studied the effect of FTY720 on CP-induced myocardial damage, and used other TRPM7 channel inhibitors nordihydroguaiaretic acid (NDGA) and Mg<sup>2+</sup> to test if any effect of FTY720 was via TRPM7 inhibition. Langendorff-perfused Wistar rat hearts were treated with FTY720 or NDGA and subjected to a CP protocol consisting of Ca<sup>2+</sup> depletion followed by Ca<sup>2+</sup> repletion. Hearts of rats pre-treated with MgSO<sub>4</sub> were also subjected to CP. Hemodynamic parameters were measured using an intraventricular balloon, and myocardial infarct size was quantified using triphenyltetrazolium chloride stain. TRPM7 proteins in ventricular tissue were detected using immunoblot analysis. FTY720, but not NDGA, decreased CP-induced infarct size. Both FTY720 and NDGA minimized the CP-induced elevation of left ventricular end-diastolic pressure, but only FTY720 ultimately improved ventricular developed pressure. Mg<sup>2+</sup> pre-treatment had effect neither on CP-induced infarct size, hemodynamic parameters during CP, nor the level TRPM7 protein expression in ventricular tissue. Overall, FTY720 attenuated CP-induced myocardial damage, with potential therapeutic implications on Ca<sup>2+</sup>-mediated cardiotoxicity. However, the cardioprotective mechanism of FTY720 seems to be unrelated to TRPM7 channel modulation.
Background: Hematological and biochemical values are widely used in veterinary clinics for disease prognosis, nutritional and therapeutic monitoring, as well as in understanding the disease process in farm animals, including equines. Aim: This study aims to assess the alterations in hematological and biochemical parameters in pure Arabian horses infested with internal parasites. Methods: Samples of feces and blood were collected from 20 adult mares. Fecal samples were proceeded by flotation test. The blood samples were analyzed for hematological and biochemical parameters to determine their means ± standard error (M ± SE). We compared the M ± SE with the reference values cited. Results: Infestation percentage was as (%) Parascaris equorum 3 (15%) and 17 (85%) mixed infestation, Strongylus species with P. equorum . The hematology of our Arabian horses shows a little variation of values compared to normal reference values, in hemoglobin level (g/dl), packed cell volume (%), red blood cell count (10 6 /μl), and white blood cells count (10 3 /μl), mean corpuscular volume (fl), mean corpuscular hemoglobin (pg) and mean corpuscular hemoglobin concentration (g/dl). In addition, their serum biochemistry showed blood glucose (mg/dl), urea (mg/dl), creatinine (mg/dl), albumin (g/dl), sodium, potassium, and chloride (mEq/l) within normal reference values. Conclusion: Our study did not show variation in hematology or chemical values compared to the normal values. We attributed this a result of the quantity and quality of nutrition given to the horses, which compensate for the damage caused by these parasites, so this study may provide useful diagnostic indices for Arabian horses.
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