The hormone erythropoietin (EPO) has been demonstrated to have cardioprotective properties. The present study investigates the role of EPO to prevent heart failure following cancer treatment with doxorubicin [adriamycin (AD)]. Male Wistar rats (150 Ϯ 10 g) were treated with saline (vehicle control group); with EPO, subcutaneously at 1,000 IU/kg body wt, three times per week for 4 wk (EPO group); with adriamycin, intraperitoneally at 2.5 mg/kg body wt, three times per week for 2 wk (AD group); and with adriamycin and EPO (EPO-AD group). Echocardiographic measurements showed that EPO-AD treatment prevented the AD-induced decline in cardiac function. Each of the hearts was then exposed to ischemia and reperfusion during Langendorff perfusion. The percentage of recovery after ischemia-reperfusion was significantly greater in EPO-AD than the AD-treated group for left ventricular developed pressure, maximal increase in pressure, and rate pressure product. The level of oxidative stress was significantly higher in AD (5 M for 24 h)-exposed isolated cardiomyocytes; EPO (5 U/ml for 48 h) treatment prevented this. EPO treatment also decreased AD-induced cardiomyocyte apoptosis, which was associated with the decrease in the Bax-to-Bcl2 ratio and caspase-3 activation. Immunostaining of myocardial tissue for CD31 showed a significant decrease in the number of capillaries in AD-treated animals. EPO-AD treatment restored the number of capillaries. In conclusion, EPO treatment effectively prevented ADinduced heart failure. The protective effect of EPO was associated with a decreased level of oxidative stress and apoptosis in cardiomyocytes as well as improved myocardial angiogenesis. apoptosis; myocardial infarction; oxidative stress THE ANTINEOPLASTIC DRUG DOXORUBICIN is effective in the treatment of a broad spectrum of malignancies, but its clinical use is limited by adverse side effects: irreversible degenerative cardiomyopathy and congestive heart failure (30, 33). The efficacy of doxorubicin [adriamycin (AD)] as a cytotoxic agent for the treatment of various human tumors prompted a search for treatments to reduce or prevent doxorubicin-induced cardiomyopathy and congestive heart failure (24). So far, however, available treatments to protect the heart from doxorubicin-induced damage have been varied and limited.The cytokine erythropoietin (EPO) is produced by the kidney and is indispensable for the proliferation, survival, and differentiation of erythroid progenitor cells (39). EPO receptors have also been identified in nonhematopoietic tissues, including the heart (34, 38). Recent studies (7,27,31) suggest that EPO also exerts a cardioprotective effect against infarction and ischemia-reperfusion injury. EPO administration before or during ischemia significantly enhanced left ventricular (LV) contractility and the recovery of cardiac function after myocardial ischemia and reperfusion injury. Several studies (8,18) suggested that EPO treatment improved ventricular contractile function in animal models of heart failure and tha...
Spectrophotometric and spectrofluorimetric methods are described for the determination of cycloserine. Both methods are based on the reaction of cycloserine in aqueous solution of pH 8.2 with p-benzoquinone. A fluorescent compound with an absorption maximum (and also an excitation maximum) at 381 nm is obtained.The complex has an apparent molar absorptivity of 4.76 x lo3 I mot-1 cm-1 and Beer's law is obeyed over the range 4-20 pg ml-1. The emission maximum of the complex is at 502 nm. The fluorescence intensity is linearly related to concentration over the range 0.04-0.2 pg ml-1. When applied to capsules labelled to contain 250 mg, the proposed methods gave mean recoveries of 100.97 k 1.14 and 99.8 k 1.13%, respectively.
Two spectrophotometric methods have been developed for the simultaneous determination of nifuroxime and furazolidone in their pharmaceutical preparations. No preliminary separation step is required in either method. The first, a modified Vierordt method, gives accurate and reproducible results for both drugs. Mean percent recoveries for nifuroxime and furazolidone were 99.50 ±1.59 and 100.20 ±1.16 (P = 0.05), respectively. This method also gives accurate and reproducible results for the determination of nifuroxime and furazolidone in their pharmaceutical preparations: Tricofuran vaginal suppositories and powder. The second method, which involves the use of the first-derivative curves, gives unreliable results; the reasons for these are discussed.
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