The present 15 days study was undertaken to evaluate the cardioprotective potential of the prenylated isoflavones osajin and pomiferin isolated from the infructences of Maclura pomifera, Moraceae, against ischemia-reperfusion induced injury in rat hearts as a model of antioxidant-based composite therapy. The study was performed on isolated, modified Langendorff-perfused rat hearts and the ischemia of heart was induced by stopping coronary flow for 30 min followed by 60 min of reperfusion (14 ml min -1 ). The Wistar rats were divided into four groups. The first treatment group received osajin (5 mg/kg/day in 0.5% Avicel); the second treatment group received pomiferin (5 mg/kg/day in 0.5% Avicel); the placebo group received only 0.5 Avicel; the last was an untreated control group. Biochemical indicator of oxidative damage-lipid peroxidation product malondialdehyde, antioxidant enzymes -superoxide dismutase, glutathione peroxidase, total antioxidant activity in serum and myocardium were evaluated. The effect of osajin and pomiferin on cardiac function, left ventricular end-diastolic pressure, left ventricular pressure and peak positive +dP/dt ischemia and reperfusion, also was examined.The results demonstrate that osajin and pomiferin attenuates the myocardial dysfunction provoked by ischemiareperfusion. This was confirmed by an increase in both antioxidant enzyme values and total antioxidant activity. The cardioprotection provided by osajin and pomiferin treatment results from the suppression of oxidative stress and this correlates with improved ventricular function.

A series of platinum(II) diiodido complexes containing 7-azaindole derivatives, having the general formula cis-[PtI2(naza)2] (1–8), has been prepared and thoroughly characterized, including X-ray structure analysis of cis-[PtI2(2Me4Claza)2]∙DMF (8∙DMF; 2Me4Claza = 2-methyl-4-chloro-7-azaindole). Complexes showed high in vitro cytotoxicity against nine human cancer cell lines (IC50 ranging from 0.4 to 12.8 μM), including the cisplatin-resistant ovarian cancer cell line (A2780R; IC50 = 1.0–3.5 μM). The results of in vivo testing, using the L1210 lymphocytic leukaemia model, at the equimolar doses of Pt with cisplatin (2 mg/kg) confirmed the activity of complex 8 comparable to cisplatin. From the mechanistic point of view, evaluated ex vivo by Western blot analyses on the samples of isolated tumour tissues, the treatment of the animals with complex 8, contrary to cisplatin, decreased the levels of tumour suppressor p53 and increased significantly the amount of intracellular anti-apoptotic protein MCL-1L (37 kDa). Additionally, the active form of caspase 3 was significantly elevated in the sample of tumour tissues treated with complex 8, indicating that the activation of p53-independent cell-death pathway was initiated. The light and electron microscopy observations of the cancerous tissues revealed necrosis as a dominant mechanism of cell death, followed by scarce signs of apoptosis. The additional results (e.g. in vitro interaction experiments with selected biomolecules, cell cycle perturbations, gel electrophoretic studies on pUC19 plasmid DNA) supported the hypothesis that the complexes might be involved in the mechanism of action quite different from cisplatin.

The purpose of the study was to monitor the antioxidative effect of morine in alloxan-induced diabetes mellitus in laboratory rat. The animals were divided by random selection into two groups (n = 7). The treated group was given morine in oral doses of 10 mg/kg -1 in 0.5% solution of Methocel E5 once a day; the control diabetic group was given only the solution of Methocel E5. Once a week, selected laboratory indices were determined in all animals (glucose, urea and cholesterol levels in serum, total glucose and protein losses through urine); diuresis as well as antioxidative enzymes (superoxiddismutase, glutathione peroxidase); total antioxidative capacity and malondialdehyde level in the blood. On the 20 th day the animals were exsanguinated and kidney tissue and pancreas samples were taken for histopathological analysis.We found a significant increase (p ≤ 0.05) of the glutathione peroxidase catalytic activity in the treated group compared to control diabetic group. There was also a highly significant increase (p ≤ 0.01) of total antioxidative capacity in the treated group compared to control diabetic group. A significant decrease (p ≤ 0.05) of malondialdehyde level was identified in the treated group compared to the control diabetic group. The superoxiddismutase catalytic activity involved nonsignificant changes. A significant decrease (p ≤ 0.05) of cholesterol level in serum was identified in the treated group compared to control diabetic group. Other examined laboratory parameters did not exhibit significant changes.Biochemical indices followed in this study indicated a protective antioxidative effect of morine. However, the results of histopathological examination did not correlate with them.

Nečas J., L. Bartošíková, T. Florian, J. Klusáková, V. Suchý, E. Janoštíková, T. Bartošík, EM. B. El Naggar: Protective Effects of Flavonoid Pomiferin on Heart IschemiaReperfusion. Acta Vet. Brno 2007, 76: 363-370.The objective of the present 15-day study was to evaluate the cardioprotective potential of fl avonoid pomiferin isolated from the infructences of Maclura pomifera, Moraceae, against ischemia-reperfusion induced injury in rat hearts as a model of antioxidant-based composite therapy. Studies were performed with isolated, modifi ed Langendorff-perfused rat hearts and ischemia of heart was initiated by stopping the coronary fl ow for 30 min, followed by 60 min of reperfusion (14 ml·min -1 ). Wistar rats were divided into three groups. The treated group received pomiferin (5 mg/kg/day in 0.5% Avicel); the placebo group received only 0.5% Avicel; the intact group was left without any applications. Biochemical indicators of oxidative damage, lipid peroxidation product malondialdehyde, antioxidant enzymes (superoxide dismutase, glutathione peroxidase, total antioxidant activity in serum and myocardium has been evaluated. We also examined the effect of pomiferin on cardiac function (left ventricular end-diastolic pressure, left ventricular pressure, peak positive +dP/dt (rate of pressure development) after ischemia and reperfusion. Our results demonstrate that pomiferin attenuates the myocardial dysfunction provoked by ischemiareperfusion. This was confi rmed by the increase in both the antioxidant enzyme values and the total antioxidant activity. The cardio-protection provided by pomiferin treatment results from the suppression of oxidative stress and correlates with the improved ventricular function.

The purpose of the study was to monitor the antioxidative effect of morine in the conditions of ischemia-reperfusion of laboratory rat kidney tissue. The animals were divided by random selection into two groups (n = 7). The treated group was given morine in peroral doses of 10 mg·kg -1 in 0.5% solution of methylcellulose (Methocel) E5 once a day, the control group was given only the solution of Methocel E5. After medication was finished on the 20 th day all animals were subject to kidney tissue ischemia (60 minutes) followed by reperfusion (10 minutes). All animals were subsequently exsanguinated, organs were recovered for histopathological examination and single identification of superoxiddismutase, glutathion peroxidase, total antioxidative capacity; and malondialdehyde level in the blood was carried out. We discovered a significant increase (p ≤ 0.05) of the superoxiddismutase catalytic activity in the treated group compared to the group of control ischemia-reperfusion. There was also a highly significant increase (p ≤ 0.01) of total antioxidative capacity in the treated group compared to the group of control ischemia-reperfusion. The glutathion peroxidase catalytic activity embodied non-significant changes when comparing the treated group and control group. A significant decrease (p ≤ 0.05) of malondialdehyde level was identified in the treated group compared to the group of control ischemia-reperfusion. The results of biochemical examination show a protective antioxidative effect of morine. The results of histopathological examination support this assumption. Antioxidants, superoxiddismutase, glutathion peroxidase, malondialdehyde