effect of treatment with nifedipine on malondiaklehyde contents, and reduced glutathione levels in serum of pre-eclamptic women

Increased lipid peroxidation and reduced anti-oxidant activity may contribute to the development of complications in pregnancy. The objective of this study was to test the hypothesis that maternal serum lipid peroxidation products are increased and anti-oxidant decreased in women with mild and moderate pre-eclampsia; and study the effect of treatment with nifedipine on the above parameters. Malondialdehyde [MDA], and reduced glutathione [GSH] were measured in maternal serum in the 3rd trimester of pregnancy, in normotensive pregnant women [n=15], mild pre-eclamptic untreated control [n=6], moderate pre-eclamptic untreated control [n=6], mild and moderate pre-eclamptic women treated with nifedipine [n=6], and [n=8], respectively. Maternal serum levels of MDA and GSH were higher and lower, respectively in both cases of pre-eclampsia when compared to normotensive pregnant controls. Treatment with nifedipine shows a significant decrease and increase, respectively in MDA contents GSH levels in serum of both cases of pre-eclampsia when compared to normal pregnant. Lipid peroxidation is involved in the pathogenesis of maternal pre-eclampsia, as evidenced by a significant increase in MDA contents and reduction of protective anti-oxidant system manifested by GSH levels. Treatment with nifedipine effectively lowers blood pressure; reduce serum MDA contents and increases serum GSH levels in pre-eclamptic women

Protective effect of melatonin against chlorpromazine-induced liver disease in rats

To evaluate the possible protective effect of orally administered melatonin against Chlorpromazine [CPZ]-induced liver disease in rats. We performed this study in the College of Pharmacy, University of Baghdad during the period from May to October 2004. The hepatoprotective effect of melatonin was studied through treatment of rats with single dose [10 mg Kg-1] orally, 7 days before and during the period of CPZ treatment, and 7 days after the induction of suspected hepatotoxicity. The parameters of oxidative stress, malondialdehyde [MDA] and glutathione [GSH] in liver tissue homogenate, activities of the liver aminotransferases, alanine transaminase [ALT] and aspartate transaminase [AST] in serum, in addition to serum level of bilirubin [total and conjugated] were evaluated. Liver tissue sections were examined to follow histological changes. Analysis of data showed that treatment with melatonin significantly attenuated the oxidative stress parameters as evidenced by lowering MDA levels in tissue homogenate while not affecting GSH levels. Serum activities of ALT, AST and serum bilirubin were normalized with both pre-treatment and post-treatment with melatonin. Data revealed that post-treatments with both saline and melatonin restore hepatic activity; however, melatonin showed significant reduction in ALT activity and bilirubin level than saline post-treatment. Additionally, histological evaluation revealed improvement of liver damage in this respect. The presented data indicated that orally administered melatonin in pharmacological doses protects against CPZ-induced liver disease in rats

effect of calcium antagonists on whole blood serotonin and platelet serotonin during pre-eclampsia

The purpose of this study was to assess the effect of calcium antagonists nifedipine and verapamil on blood pressure levels and the level of serotonin in both whole blood and platelets in 6 pregnant women with mild pre-eclampsia and 8 pregnant women with moderate pre-eclampsia treated with 10 mg oral dose nifedipine twice daily, while 5 pre-eclampsia pre-eclamptic women in each mild and moderate cases treated with 40 mg verapamil three times daily. The women received their specific treatment until the day of delivery. Data analysis revealed a significant decrease in systolic, diasrolic and mean arterial blood pressure in each treatment regimen compared with pre-treatment values in both mild and moderate cases. Considering whole blood 5-HT, administration of both calcium antagonists causes a significant decrease in the level of whole blood 5-HT in mild pre-eclampsia after 3- days treatment; while in moderate case there is a significant decrease after 3-days treatment with nifedipine and 6-days treatment after verapamil. Platelet serotonin level was significantly increased in mild case after 3-days of both treatments; while in moderate case, platelet serotonin level was increased after 3-days treatment with nifedipine and 6-days treatment with verapamil as compared to pre- treatment level. These observations suggest that calcium antagonists may be effective in reducing elevated blood pressure in pre-eclampsia patients and that serotonin may play a role in the pathogenesis of pre -eclampsia. Serotonin is widely distributed in nature being found in plants and animals. In human, over 90% of the serotonin is found in enterochromaffin cell in the G.I.T. The overflowing of 5-HT from cells into the blood is removed actively by the liver and the endothelium, specially in the lung. The 5-HT taken up by the endothelial cells is destroyed enzymatically by mono-amine oxidase. Most of the 5-HT escaping hepatic and pulmonary metabolism is taken up by the platelets. Serotonin activates human blood platelets by combining with specific receptors on the membrane, seems to be of the 5-HT2-type [Leysen etal., 1982]. 5-HT; receptors type also identified on vascular smooth muscle and bronchial smooth muscle, their stimulation provoked smooth muscle contraction [Vanhoutte et al., 1983], which also suggest that serotonin in hypertensive human and animal play a role in the maintenance of the chronic increase in peripheral resistance. Pre-eclampsia is associated with the increased maternal placental Vascular resistance and elevated blood pressure has been considered as a compensatory to maintain placental perfusion. Therefore antihypertensive treatment in these patients should cause uterine vasodilatation in order to avoid diversion of the placental circulation. Calcium channel blockers of the dihydropyridine group [nifedipine] characterized by their ability to influence transmembrane calcium influx. These are clinically useful peripheral vaso dilators effects and seen effective in lowering maternal Mood pressure in pre-eclampsia [Constantin et al., 1987; Barton etal., 1990]. In 1993, Lechner demonstrated an excellent uterus-relaxing properties of verapamil in addition to their efficacy as hypotensive agents in the treatment of pre-eclampsia

effect of calcium antagonists in controlling hypertension and its relation to the increased level of lipid peroxidation during pre-eclampsia

Thirty nine out patients with pre-eclampsia from Abu-Ghraib hospital were involved in this study to test the effect of calcium antagonists [nifedipine and verapamil] in lowering blood pressure and its relation to serum lipid peroxidation and serum glutathione level. Oral administration of each drugs resulted in lowering blood pressure, a decrease in the level of lipid peroxidation [decrease in MDA] concentration, and in increase serum GSH level. These observation suggest that, calcium antagonists may be effective in acutely reducing elevated blood pressure in pre-eclamptic patients, and that lipid peroxidation may play a role in the etiology of pre-eclampsia. pre-eclampsia, is a clinical syndrome which complicates pregnancy afer the twentieth weeks of gestation, is characterized by hypertension. Proteinuria, and edema [Whigham, 1978]. The etiology of it remains obscure. It has been suggested that lipid peroxidation may be involved [Hubel et al., 1989; Uotila et. al., 1993]. The pathologic features of pre-eclampsia were general agreement exists is that the syndrome is characterized by a decrease in PGI[2]: TXA[2] ratio. The cause of the decline is unknown but may have a genetic component [Moncada and Vane, 1979]. In 1985, Walsh demonstrated that the placenta of pre-eclamptic women produce a greater generation of TXA[2] about three times as much TXA[2] as the normal placenta. This study contrasted with the production rates of PGL[2]. Because of the biological actions of these eicosasnoids, this imbalance could significantly contribute to the increased vaso-constriction, platelet aggregation, increased lipid peroxide generation and reduced utero -placental blood flow characterized of pre-eclampsia [Saleh et al., 1987; Hubel et al., 1989]. The antihypertensive effect of calcium antagonists should cause uterine vasodilatation [Guazzi et al., 1983] and may have a role in inhibition of TXA[2] [Mehta, 1985]. This investigation was designed to evaluate the efficacy of calcium antagonists in controlling hypertension and its relation to the increased to the increased level of lipid peroxidation during pre-eclampsia.