Impact of selenium on the leukotriene B4 synthesis pathway during isoproterenol-induced myocardial infarction in experimental rats.

Selenium (Se), an essential micronutrient, exerts its biological functions through selenoproteins. There are evidences that show Se to have an impact on the course and outcome of a number of etiologically inflammatory diseases. Leukotriene B(4) (LTB(4)) is an inflammatory mediator, and its production is mediated through two specific enzymes--lipooxygenase (LOX) and leukotriene A(4) hydrolase (LTA(4)H). We examined the effect of Se on LTB(4) synthesis during isoproterenol (ISP)-induced myocardial infarction (MI) in rats. Rats were divided as: control, ISP, Se, and Se + ISP. Sodium selenite was administered at dose of 8 µg/100 g/day. ISP was injected subcutaneously twice (10 mg/100 g body weight). The rats pretreated with Se had increased concentration of phospholipids and enhanced biosynthetic enzymes compared with that of ISP. The activities of phospholipases decreased on Se treatment. The level of calcium was increased in ISP group whereas, on Se treatment, it was near normal levels. Activities of LOX and expression of LTA(4)H were down-regulated in the case of Se-pretreated rats. Our study shows the anti-inflammatory mechanism of selenium during MI.

Spermicidal action of a protein isolated from ethanolic root extracts of Achyranthes aspera: an in vitro study.

A previous study conducted in our department, showed that 50% ethanolic extract of the roots of Achyranthes aspera possess spermatotoxic effects. Preliminary studies also revealed that the active principle may be a protein. In this study a 58 kDa Achyranthes protein (Ap) was isolated from Achyranthes aspera using standard protocols and their effects on the rat sperm was studied in vitro in comparison with nonoxynol-9 (N-9). The sperm immobilization studies showed that about 150 µg of Ap was able to immobilize sperms completely within seconds at a lower concentration than N-9 (250 µg). The sperm revival test revealed that the spermicidal effect was irreversible. There was also a significant reduction in sperm viability and hypo-osmotic swelling in the Ap-treated and N-9 treated groups in comparison to the control. In the Ap and N-9 treated groups the number of acrosome reacted cells were found to be high and it also caused agglutination of the sperms indicating the loss of intactness of the plasma membrane which was further supported by the significant reduction in the activity of membrane bound 5' nucleotidase and acrosin enzyme. Hence this study showed that the protein isolated from the roots of Achyranthes aspera possess spermicidal activity in vitro and can act as a spermicide similar to that of nonoxynol 9. Ap also possessed spermicidal activity against human sperms in vitro.

Effects on spermatogenesis in swiss mice of a protein isolated from the roots of Ricinus communis (Linn.) (Euphorbiaceae).

This study was aimed to evaluate the effect on spermatogenesis of a 62 kDa protein (Rp) isolated from 50% ethanolic extract of the root of Ricinus communis in mice. A dose response study in mice revealed that 25mg/kg body weight/day was the most effective dose. Swiss strain mature male mice of 30 days old were divided into two group namely control and Rp treated (25mg/kg body weight/day). The study showed that sperm motility and count were decreased significantly in the treated group as compared to the control. The fertility index of the treated groups was reduced by 100%. The activity of HMG Co A reductase and cholesterol were increased significantly in the treated group. The testicular activities of 3ßHSD, 17ßHSD, glucose 6-phosphate dehydrogenase and malic enzyme and the level of serum testosterone were decreased significantly in the treated group. The expression of 3ßHSD and 17ßHSD were decreased and the expression of StAR increased significantly in the treated group as compared to the control. Proteolytic digestion of the native protein with trypsin and chymotrypsin showed that the proteolytic cleavage did not affect the spermicidal action of Rp. Hence this study can be concluded that Rp impaired spermatogenesis in vivo by suppressing the production of testosterone.

The Ayurvedic drug, Ksheerabala, ameliorates quinolinic acid-induced oxidative stress in rat brain.

One of the mechanisms of neurotoxicity is the induction of oxidative stress. There is hardly any cure for neurotoxicity in modern medicine, whereas many drugs in Ayurveda possess neuroprotective effects; however, there is no scientific validation for these drugs. Ksheerabala is an ayurvedic drug which is used to treat central nervous system disorders, arthritis, and insomnia. The aim of our study was to evaluate the effect of Ksheerabala on quinolinic acid-induced toxicity in rat brain. The optimal dose of Ksheerabala was found from a dose escalation study, wherein it was found that Ksheerabala showed maximum protection against quinolinic acid-induced neurotoxicity at a dose of 15 microL/100 g body weight/day, which was selected for further experiments. Four groups of female albino rats were maintained for 21 days as follows: 1. Control group, 2. Quinolinic acid (55 microg/100 g body weight), 3. Ksheerabala (15 microL/100 g body weight), 4. Ksheerabala (15 microL/100 g body weight) + Quinolinic acid (55 microg/100 g body weight). At the end of the experimental period, levels of lipid peroxidation products, protein carbonyls, and activities of scavenging enzymes were analyzed. The results revealed that quinolinic acid intake caused enhanced lipid and protein peroxidation as evidenced by increased levels of peroxidation products such as malondialdehyde, hydroperoxide, conjugated dienes, and protein carbonyls. On the other hand, the activities of scavenging enzymes such as catalase, superoxide dismutase (SOD), glutathione peroxidase, and glutathione reductase as well as the concentration of glutathione were reduced. On coadminstration of Ksheerabala along with quinolinic acid, the levels of all the biochemical parameters were restored to near-normal levels, indicating the protective effect of the drug. These results were reinforced by histopathological studies.

Antiperoxidative and antiinflammatory effect of Sida cordifolia Linn. on quinolinic acid induced neurotoxicity.

Sida cordifolia is a plant belonging to the Malvaceae family used in many ayurvedic preparations. This study aimed at assessing the effects of ethanolic extract of Sida cordifolia root on quinolinic acid (QUIN) induced neurotoxicity and to compare its effect with the standard drug deprenyl in rat brain. Rats were divided into six groups: (1) control group (2) QUIN (55 microg/100 g bwt/day) (3) 50% ethanolic plant extract treated group (50 mg/100 g bwt/day) (4) Deprenyl (100 microg/100 g bwt/day) (5) QUIN (55 microg/100 g bwt/day) + 50% ethanolic plant extract treated group (50 mg/100 g bwt/day) (6) QUIN (55 microg/100 g bwt/day) + Deprenyl (100 microg/100 g bwt/day). At the end of the experimental period a status of lipid peroxidation products, protein peroxidation product, activities of the scavenging enzymes and the activities of the inflammatory markers were analyzed. Results revealed that the lipid peroxidation products decreased and the activities of the scavenging enzymes increased significantly in the brain of the plant extract treated group, deprenyl treated group and also in the coadminstered groups. The activities of markers of inflammatory responses such as cyclooxygenase and lipoxygenase were found to be significantly increased in the QUIN treated rats and this was decreased upon the administration of plant extract and deprenyl. In short, the study revealed that 50% ethanolic extract of Sida cordifolia has got potent antioxidant and antiinflammatory activity and the activity is comparable with the standard drug deprenyl.

Impact of selenium on NFκB translocation in isoproterenol-induced myocardial infarction in rats.

NFκB is a major transcription factor that controls the expression of various genes. Its activation is a complex process that can be triggered by many agents and one among them is reactive oxygen species. The aim of this study was to investigate the effect of selenium on NFκB activation in rats induced with myocardial infarction by isoproterenol (ISP). The markers of myocardial infarction showed increased activity in the serum of rats induced with ISP compared to the group that was pretreated with selenium along with ISP. Cellular selenium status was also found to be very low in the ISP-induced group of rats. The concentration of cytosolic NFκB was comparatively lower in the ISP group than in the group treated with selenium and ISP. Whereas higher levels of NFκB were found in the nuclear extract of the ISP-treated animals than in the selenium + ISP group. Elevated levels of malondialdehyde, hydroperoxides, and conjugated diens in the ISP-treated rats revealed the higher levels of oxidative stress in this group. Thus, our studies reveal the inhibitory effect of selenium in the nuclear translocation of NFκB during myocardial infarction. Histopathological studies of the heart also support the cardioprotective role of selenium.

Protective effect of selenium on nicotine-induced testicular toxicity in rats.

Effect of exogenous selenium at a dose of 10 mug/kg body weight on the testicular toxicity induced by nicotine in rats was investigated. Male albino rats were maintained for 60 days as follows: (1) control group (normal diet), (2) nicotine group (0.6 mg /kg body weight), (3) selenium (10 microg/kg body weight), and (4) nicotine (0.6 mg/kg body weight) + selenium (10 microg/ kg body weight). Administration of nicotine caused reduction in sperm count and sperm motility. Activity of HMG CoA reductase and concentration of cholesterol were increased in the testes of the nicotine administered group. Activities of testicular enzymes 3beta hydroxysteroid dehyrogenase (3 betaHSD), 17beta hydroxysteroid dehyrogenase (17 betaHSD) were decreased. Levels of testosterone in the serum were also reduced. However, the extent of these alterations was lesser in the group administered with nicotine along with selenium. Analysis of plasma revealed reduced quantity of cotinine in the group co-administered with nicotine along with selenium in comparison with the nicotine group. Nondetectable levels of nicotine were present in the co-administered group. This indicates altered metabolism of nicotine when administered along with selenium.

Effect of exogenous selenium on the testicular toxicity induced by ethanol in rats.

The effects of supplementation of selenium at a dose of 10 microg/ kg body weight were investigated on ethanol induced testicular toxicity in rats. In the present study, four groups of male albino rats were maintained for 60 days, as follows: (1) Control group (normal diet) (2) Ethanol group (4g/kg body weight) (3) Selenium (10 microg/kg body weight) (4) Ethanol + Selenium (4g/kg body weight + 10 microg/kg body weight). Results revealed that ethanol intake caused drastic changes in the sperm count, sperm motility and sperm morphology. It also reduced the levels of testosterone and fructose. The activities of 3betaHSD, 17betaHSD in the testis and SDH in the seminal plasma were also reduced. Lipid peroxidation was also enhanced as the lipid peroxidation products were increased and the activities of the scavenging enzymes were reduced. But on coadministration of selenium along with alcohol all the biochemical parameters were altered to near normal levels indicating a protective effect of selenium. These results were reinforced by the histopathological studies.