In 1981, Henry and Bentley first reported that nifedipine suppressed experimental atherosclerosis without inhibiting hypercholesterolemia in cholesterol-fed rabbits. Numerous studies have since been performed to determine whether calcium antagonists, a heterogenous group of compounds, possess significant anti-atherogenic activity; however, their efficacy in this respect remains controversial. Even if they are effective in controlling the development of atherosclerotic lesions, their observed effects in this respect may be unrelated to their effects on voltage-dependent Ca2+ channels. Rather, they may be due to nonspecific hemodynamic effects, in that other antihypertensive agents, such as reserpine, guanethidine, propranolol, metoprolol, and doxazosin, are also reported to be effective in controlling experimental atherosclerosis in normotensive and hypertensive animals. Comparative studies on calcium antagonists versus other antihypertensive agents are required to determine whether the benefit derived from the calcium antagonists in experimental atherosclerosis is specific for these antagonists.
Mitochondria are one of the possible sources of potentially harmful reactive oxygen species in tissue during ischemia-reperfusion. In order to delineate the capacity of the respiratory chain to produce reactive oxygen species, the effect of respiratory inhibitors on the oxygen uptake and luminol and lucigenin enhanced chemiluminescence was measured in isolated blood-free perfused rat livers. Concomitant tissue damage was monitored by measuring the release of lactate dehydrogenase and thiobarbituric acid reactive substances by the livers. Cyanide inhibited oxygen uptake reversibly while rotenone and Antimycin A effects were not reversible. Enhanced chemiluminescence was increased immediately by cyanide, suggesting increased formation of reactive oxygen species. Antimycin A produced a delayed, large increase in chemiluminescence concurrent with severe cell damage and increased lipid peroxidation; Cyanide and rotenone induced only limited cell damage. The cell damaging effect of Antimycin A was delayed by the simultaneous administration of cyanide. These results are discussed in terms of the possible role of reactive oxygen species produced during Antimycin A inhibition of the respiratory chain in cell damage.
Absorption and transport of 5-methyltetrahydrofolate, the dietary form of the vitamin after intestinal hydrolysis, was studied in rat everted small intestinal segments. The folate transport from the mucosal to the serosal compartment was pH dependent and optimal at experimental pH4.0, and the transport was only 40-50% of that level at the physiological pH of the gut, i.e., 6.5-7.0. The methyltetrahydrofolate transport to the serosal site was not linked with any cotransport with H+, but the optimum transport was dependent on the mucosal acidic pH of 4 irrespective of the serosal pH. Methyltetrahydrofolates were, however, bound to their mucosal cell receptor optimally at pH6.5. Addition of ATP at the mucosal site enhanced mucosal to serosal folate transport at pH6.5 of the gut. A role for an intestinal mucosal Mg+-ATPase in the hydrolysis of ATP and formation of an acidic microclimate were observed. Sodium azide, an inhibitor of Mg+-ATPase, hindered methyltetrahydrofolate transport at pH6.5 but not at pH4.0. The overall results suggest that 5-methyltetrahydrofolate is absorbed in the intestine by a passive process in an acid microclimate at pH4.0 generated by intestinal mucosal brush-border Mg+-ATPase.
An aqueous extract of defatted leaves of Azadirachta indica was found to possess trypanocidal activity against Trypanosoma brucei brucei. Column chromatography of the crude extract gave three fractions, I, II, and III, that eluted with ethylacetate/methanol, benzene/methanol, and acetic acid/methanol, respectively. Of these extracts, only fraction III retained trypanocidal properties and cured mice chronically infected with Trypanosoma brucei brucei. Histopathological studies of the brains, livers, hearts, and spleens of the treated mice showed no cellular infiltrations. These findings are discussed in relation to trypanosome chemotherapy.
The protective effect of chlorogenic acid, which occurs in tea leaves and coffee beans, on lipid peroxidation induced in the liver of rats by the administration of carbon tetrachloride or by 60Co-irradiation was examined. When chlorogenic acid was administered once a day for 3 successive days before the administration of carbon tetrachloride, the substance suppressed the increase in lipid peroxide level in the liver. The leakage into the bloodstream of glutamate oxaloacetate and glutamate pyruvate transaminases from the liver was also suppressed, and this finding was supported by morphological observations. When rats administered chlorogenic acid once a day for 5 successive days were irradiated with 60Co once a day for the last three days, the increase in serum and liver lipid peroxide levels was significantly suppressed as compared with the control.
The present study evaluated the efficacy of taurine and niacin alone and in combination, in ameliorating the early lung injury found in paraquat-administered rats. At 24h after paraquat insult several biochemical indicators in bronchoalveolar lavage fluid were analyzed. Increases in total protein, albumin, lactate, lactate dehydrogenase, Nacetyl-β-D-glucosaminidase, alkaline phosphatase, acid phosphatase, and angiotensin-converting enzyme were evident in bronchoalveolar lavage fluid of paraquat-intoxicated rats. Serum and lung lipid peroxidation products were also found to be elevated in the paraquat rats. Pretreatment with taurine or niacin for 7 days before paraquat intoxication reduced the incidence of lung injury; however, far more dramatic protective effects was observed in combined treatment with taurine and niacin. A significant reduction in biochemical constituents in bronchoalveolar lavage fluid and lipid peroxidation occurred in paraquat groups pretreated with taurine and niacin. We conclude that taurine and niacin administration has a protective effect against paraquat-induced early lung injury through the beneficial effects of their antioxidant and membrane-stabilizing properties.
The effect of ellagic acid on lipid peroxide levels was examined in the placenta and fetus of pregnant rats irradiated with 60Co Upon whole body irradiation with 60Co (10Gy or 30Gy), the lipid peroxide levels in the placenta, in the liver and brain of the fetus, and in the serum, liver, spleen, and brain of the pregnant rat were significantly increased one day after the irradiation. When ellagic acid was administered either through a stomach tube or by intraperitoneal injection to the rat for 4 successive days before the irradiation, the increase in lipid peroxide levels in these samples, except for the brain of the pregnant rat, was significantly prevented. The effect on the placenta and fetus paralleled that found in the pregnant rat. By the administration of ellagic acid, the morphological changes such as degeneration of vascular endothelial cells of the placenta and liver cells of the fetus caused by the irradiation were prevented. The survival rate of the fetus after the irradiation was improved by ellagic acid. The effects of ellagic acid were approximately the same as those of α-tocopherol.
Differences in serum lipids, apoprotein levels, and fatty acid compositions were investigated in normal and hyperlipidemic female subjects in a rural area of Japan. Compared with normolipidemic subjects, hyperlipidemic ones of type IIa showed only slight differences in fatty acid composition in the cholesterol ester fraction. Also compared with normolipidemic subjects, the type IIb group had a lower proportion of 18:2 fatty acids in the phospholipid fraction, while 16:1 and 18:1 fatty acids were higher and 18:2 fatty acids were lower in the cholesterol ester fraction. Regarding type IV hyperlipidemics vs. normolipidemics, differences were evident in that in the former percentages of 18:2 fatty acids were lower in the cholesterol ester, phospholipid, and triglyceride fractions, while the percentages of 16:0 fatty acids were higher in the cholesterol ester and triglyceride fractions and that of 22:6 fatty acid in the phospholipid fraction was higher. Dietary fatty acid composition and cholesterol intake did not differ significantly among the groups.