Therapeutic effects of gold nanoparticles synthesized using Musa paradisiaca peel extract against multiple antibiotic resistant Enterococcus faecalis biofilms and human lung cancer cells (A549).

Botanical-mediated synthesis of nanomaterials is currently emerging as a cheap and eco-friendly nanotechnology, since it does not involve the use of toxic chemicals. In the present study, we focused on the synthesis of gold nanoparticles using the aqueous peel extract of Musa paradisiaca (MPPE-AuNPs) following a facile and cheap fabrication process. The green synthesized MPPE-AuNPs were bio-physically characterized by UV-Vis spectroscopy, FTIR, XRD, TEM, Zeta potential analysis and EDX. MPPE-AuNPs were crystalline in nature, spherical to triangular in shape, with particle size ranging within 50 nm. The biofilm inhibition activity of MPPE-AuNPs was higher against multiple antibiotic resistant (MARS) Gram-positive Enterococcus faecalis. Light and confocal laser scanning microscopic observations evidenced that the MPPE-AuNPs effectively inhibited the biofilm of E. faecalis when tested at 100 µg mL-1. Cytotoxicity studies demonstrated that MPPE-AuNPs were effective in inhibiting the viability of human A549 lung cancer cells at higher concentrations of 100 µg mL-1. The morphological changes in the MPPE-AuNPs treated A549 lung cancer cells were visualized under phase-contrast microscopy. Furthermore, the ecotoxicity of MPPE-AuNPs on the freshwater micro crustacean Ceriodaphnia cornuta were evaluated. Notably, no mortality was recorded in MPPE-AuNPs treated C. cornuta at 250 µg mL-1. This study concludes that MPPE-AuNPs are non-toxic, eco-friendly and act as a multipurpose potential biomaterial for biomedical applications.

Preeclamptic cord blood hemolysis and the effect of Monascus purpureus and Saccharomyces cerevisiae in modulating preeclamptic stress.

BACKGROUND: Preeclampsia is associated with impaired antioxidant defense that results in materno- fetal complications. In addition to antioxidant deficiency, hemolytic disorder has also been observed in preeclamptic mother. METHODS: This study aims in analyzing the fetal complications using cord blood RBC (red blood cell); further the antihemolytic and antioxidant efficiency of two common probiotic yeasts Monascus purpureus and Saccharomyces cerevisiae in preeclamptic and normotensive RBCs were assessed. RESULTS: There was a significant decrease in the antioxidant status (p<0.05) with increased oxidative stress, nitrative stress (p<0.05) and hemolysis (p<0.001) in preeclamptic RBC comparatively. M. purpureus demonstrated a highly significant reactive oxygen radical scavenging activity (p<0.001) whereas S. cerevisiae exhibited a highly significant nitric oxide radical scavenging activity (p<0.001). It was noted that oxidative stress hemolysis was decreased with increased antioxidant level in cord blood RBC from both samples after incubation with both yeasts in a similar manner. The antihemolytic property of M. purpureus and S. cerevisiae suggests that S. cerevisiae functions efficiently with increasing stress. CONCLUSION: This study demonstrates for the first time that despite their differential scavenging activities, a diet rich in M. purpureus and S. cerevisiae could equally serve as a good natural supplement to alleviate the stress status in the preeclamptic fetus (Tab. 4, Fig. 1, Ref. 39).

Formulation and evaluation of solid lipid nanoparticles of ramipril.

Solid lipid nanoparticles are typically spherical with an average diameter between 1 and 1000 nm. It is an alternative carrier system to tradition colloidal carriers, such as, emulsions, liposomes, and polymeric micro and nanoparticles. Ramipril is an antihypertensive agent used in the treatment of hypertension. Its oral bioavailability is 28% and it is rapidly excreted through the renal route. This drug has many side effects such as, postural hypotension, hyperkalemia, and angioedema, when given as an immediate dosage form. To overcome the side effects and to increase the bioavailability of ramipril, solid lipid nanoparticles of ramipril are prepared by using lipids (glyceryl monostearate and glyceryl monooleate) with stabilizers (tween 80, poloxamer 188, and span 20). The prepared formulations have been evaluated for entrapment efficiency, drug content, in-vitro drug release, particle size analysis, scanning electron spectroscopy, Fourier transform-infrared studies, and stability. A formulation containing glyceryl monooleate, stabilized with span 20 as surfactant showed prolonged drug release, smaller particle size, and narrow particle size distribution, as compared to other formulations with different surfactants and lipids.

A reversal by L-arginine and sodium nitroprusside of ageing-induced memory impairment in rats by increasing nitric oxide concentration in the hippocampus.

In the present study, memory formation to an acquired pole-climbing shock avoidance task was tested in young adult (3-4 month-old) and aged (24-25 month-old) rats. The data were correlated with the activity of nitric oxide synthase (NOS) and the concentration of nitric oxide (NO) in the hippocampus, midbrain, cortex and cerebellum. Motor co-ordination was tested in both groups. Memory test and NO determination were carried out in another set of young and aged groups, 15 min after intraperitoneal administration of NO precursor, L-arginine (500, 1000 mg/kg) or NO donor, sodium nitroprusside (SNP) (1.25, 2.5 mg/kg). No difference was found between the motor co-ordination performances of young and aged animals. But the aged animals were not able to perform the shock avoidance pole-climbing task as readily as the young animals. It is suggestive of an impairment of memory formation of the acquired task in the aged animals. The synthesis of NO which is known to regulate memory process in the hippocampus, was lower in this brain region of aged animals as compared to that in young animals. L-arginine (1000 mg/kg) and SNP (2.5 mg/kg) increased the concentration of NO in the hippocampus and shortened the time of pole-climbing shock avoidance task in young as well as in aged animals. These results lead to a conclusion that a decreased synthesis of NO in the hippocampus in responsible for an impairment of memory formation in aged animals and that an increase in the concentration of NO in the hippocampus by L-arginine (1000 mg/kg) or SNP (2.5 mg/kg) results in a promotion of memory formation in the young adult rats and a reversal of memory deterioration in the aged animals. Thus, NO precursor and NO donor may be effective in reverting cognitive dysfunction associated with Alzheimer's disease, an ageing-induced neurodegenerative disease.

The effect of L-arginine on the memory impairing action of phenobarbitone in rats that convulsed after the injection of picrotoxin.

Nitric oxide (NO) has been demonstrated to enhance memory formation in experimental animals. However, the effect of NO precursor, L-arginine has never been tested on the memory impairing action of the aniepileptic drug, phenobarbitone independently and concurrently with the convulsant, picrotoxin (PCT). In view of this, in the present study, rats that acquired the shock avoidance task were treated with PCT (5 mg/ kg). Twenty four h later these animals were injected with L-arginine (500, 1000 mg/kg) and phenobarbitone (10, 20 mg/kg). Retention of the acquired task was tested 30 min later. The effect of these compounds were correlated with the changes produced by them on the concentration of NO in the brain. PCT and phenobarbitone (20 mg/kg) inhibited memory process independently and concurrently. NO concentration was not altered by phenobarbitone but was decreased in PCT-treated animals. L-arginine (1000 mg/kg) increased the concentration of NO in PCT and phenobarbitone treated animals and prevented these compounds from impairing memory process independently and concurrently. These results lead to a conclusion that L-arginine may be used in combination with phenobarbitone to prevent both the cognitive side effect of the antiepileptic drug and the impairment of memory that is associated with the convulsion disorder.

Demonstrating the dose- and time-related effects of 7-nitroindazole on picrotoxin-induced convulsions, memory formation, brain nitric oxide synthase activity, and nitric oxide concentration in rats.

In this study, the dose (50, 100, 150, and 200 mg/kg)- and time (30 and 60 min)- related effects of 7-nitroindazole (7-NI), a neuronal specific inhibitor of nitric oxide synthase (NOS) were tested on picrotoxin (5 mg/kg)-induced convulsions and memory formation in rats. The changes produced by these doses of 7-NI were determined on NOS activity and nitric oxide (NO) concentration in the brain. The effects of 7-NI were tested in animals pretreated (30 min) with L-arginine (500 and 1000 mg/kg). 7-NI, at 50 and 100 mg/kg, did not produce significant changes in NOS activity and NO concentration in the brain and memory formation. However, the convulsant action of picrotoxin was inhibited in a dose-dependent manner in these animals. A time-dependent decrease in the activity of NOS and the concentration of NO, a promotion of picrotoxin-induced convulsions, and an impairment of memory were found in animals treated with 150 and 200 mg/kg of 7-NI. The larger and not the smaller dose of L-arginine raised the concentration of NO, inhibited picrotoxin-induced convulsions and promoted memory process. Either dose of L-arginine failed to prevent 50 and 100 mg/kg of 7-NI from inhibiting convulsions. The effects of the larger doses of 7-NI (150 and 200 mg/kg) were effectively prevented by the increase of NO and not the ineffective dose of L-arginine. These results suggest that 7-NI (50 and 100 mg/kg) decreases convulsions by a nonspecific mechanism and that an inhibition of NOS by the larger doses of it (150 and 200 mg/kg) results in proconvulsant action and memory impairment. The data further show that the margin between the protective and proconvulsant doses of 7-NI is relatively narrow. These results have been taken together with the earlier reports that 7-NI produces learning impairment and fails to increase the anticonvulsant effect of traditional antiepileptic agents on experimentally induced convulsions to conclude that 7-NI can never emerge as an anticonvulsant agent for clinical use.

Prevention of picrotoxin convulsions-induced learning and memory impairment by nitric oxide increasing dose of L-arginine in rats.

Learning and memory processes were tested in adult male rats using a traditional pole-climbing apparatus 30 min after the administration of L-arginine (500 and 1000 mg/kg), the precursor of nitric oxide (NO), and N-nitro-L-arginine methyl ester (L-NAME) (50 and 100 mg/kg), the inhibitor of NO synthesis. The effects of the convulsant (5.0 mg/kg) and a smaller nonconvulsant (2.5 mg/kg) dose of picrotoxin were tested on learning and memory 120 min and 24 h after their administration. The tests were carried out 30 min after L-arginine in animals treated 120 min previously with the convulsant dose of picrotoxin. A dose-dependent enhancement and an inhibition of learning and memory were observed in animals treated with L-arginine and L-NAME, respectively. The convulsant dose of picrotoxin impaired both learning and memory processes. The effect of picrotoxin was reverted following the administration of L-arginine (1000 mg/kg). An interpretation of these results indicates that convulsions induced by picrotoxin produces learning and memory impairment, and that this defect is reversible if NO synthesis is increased in the brain by the systemic administration of L-arginine.

Effect of 7-nitroindazole alone and in combination with phenobarbitone and diazepam on picrotoxin-induced convulsions in rats.

There are no reports on the effect of 7-nitroindazole (7-NI) on chemically-induced convulsions. Hence, in the present study, its (100 and 200 mg/kg) action was tested alone and in combination with phenobarbitone (20 mg/kg) and diazepam (0.25 mg/kg) on picrotoxin (PCT)-induced convulsions in rats. The changes produced by 7-NI on nitric oxide synthase (NOS) activity and nitric oxide (NO) concentration were determined in the brain. The effect of 7-NI was tested in L-arginine (1000 mg/kg) pretreated (30 min) animals. The smaller dose (100 mg/kg) of 7-NI did not alter NOS activity and NO concentration, but inhibited PCT-induced convulsions indicating that its anticonvulsant action was devoid of an involvement of NO. But, an inhibition of NOS activity, by a larger (200 mg/kg) dose of it, resulted in a promotion of the convulsant action of PCT and in an impairment of the anticonvulsant effect of both phenobarbitone and diazepam. The proconvulsant action of 7-NI was reverted by L-arginine. These results suggest that 100 and 200 mg/kg of 7-NI produce distinguishable action on PCT-induced convulsions because NOS activity is inhibited by 200 mg/kg and not by 100 mg/kg of it. The results further suggest that NO acts as anticonvulsant and that the NOS inhibitors, like 7-NI, cannot be used as an anticonvulsant either alone or in combination with other anticonvulsants.

Modulation of fluoride toxicity in rats by calcium carbonate and by withdrawal of fluoride exposure.

In order to assess the effect of calcium on the toxic effects of fluoride, adult female Wistar rats were treated with sodium fluoride (NaF, 500 ppm in drinking water) alone or in combination with calcium carbonate (CaCO3, 50 mg/ kg by oral intubation) daily for 60 days. Food, water and fluoride intake were measured daily for 60 days. Body weight gain, exploratory motor activity, rota-rod motor coordination, dental structure, activities of acetylcholinesterase (AchE, brain and skeletal muscle) and Na+ K+ ATPase (erythrocyte membrane and skeletal muscle) and the concentrations of protein (serum and skeletal muscle), calcium (serum) and fluoride (serum) were determined in these animals 24 hr after the last treatment. The same parameters were tested in another group, 60 days after withdrawal of NaF exposure (500 ppm in drinking water daily for 60 days). NaF treatment decreased food and water intake, reduced body-weight gain and impaired exploratory motor activity and rota-rod performance. Dental lesions, inhibition of the activities of AchE and N+ K+ ATPase and a decrease in the concentration of protein, and serum calcium were also observed in these animals. These effects were accompanied by a marked elevation of fluoride concentration in the serum. CaCO3 decreased the concentration of fluoride in the serum of NaF-treated animals. A decrease in serum fluoride concentration was found also after NaF withdrawal. A prevention of locomotor behavioural, biochemical and dental toxicities of fluoride was observed both in these groups. It is concluded that the dose of CaCO3 used in the present study has a potential to prevent the toxicity of fluoride by maintaining serum fluoride at a less toxic level. Further, the toxic effects of fluoride are reversible if its exposure is withdrawn for 2 months.

Calcium preventing locomotor behavioral and dental toxicities of fluoride by decreasing serum fluoride level in rats.

Spontaneous motor activity, rota-rod performance (motor co-ordination), body weight gain, food intake, activities of total cholinesterase (blood) and acetylcholinesterase (brain), and dental structure were determined in adult female rats treated with a very high dose of sodium fluoride (500 ppm in drinking water) alone and in combination with calcium carbonate (50 mg/kg body weight by oral intubation) for 60 days. The concentration of fluoride and calcium were measured in the serum of these animals. Administration of sodium fluoride with drinking water produced both behavioural and dental toxicities and not lethality in the present study. A suppression of spontaneous motor activity, a shortening of rota-rod endurance time, a decreased body weight gain and food intake, a suppression of total cholinesterase and acetylcholinesterase activities and dental lesion were observed in test animals. Serum fluoride concentration was raised markedly and that of calcium was decreased in these animals. The effects of sodium fluoride were prevented significantly when animals received calcium carbonate along with sodium fluoride. Serum fluoride content was decreased and that of calcium was restored to control level in these animals. These results indicate that calcium prevents not only fluoride-induced hypocalcemia but also the locomotor behavioral and dental toxicities of fluoride by decreasing bioavailability of fluoride.

Effects of sodium fluoride on locomotor behavior and a few biochemical parameters in rats.

Spontaneous motor activity and motor coordination were tested in adult female rats after treating with sodium fluoride at 20 or 40 mg/kg dose level daily for 60 days, using an activity chamber and a rota-rod apparatus, respectively. Total protein concentrations were determined in skeletal muscle, liver and serum of similarly treated animals. The activities of total cholinesterase and acetylcholinesterase were determined in blood and brain regions, respectively. Sodium fluoride treatment suppressed spontaneous motor activity. But no change was observed in the motor coordination of these animals. Tissue and serum protein concentrations were decreased. Cholinesterase activity was decreased in the blood and not in brain regions. A failure of sodium fluoride to impair motor coordination indicated that neuromuscular function required for a forced task was not deteriorated in these animals, although skeletal muscles were deprived of protein and blood cholinesterase activity was suppressed. A suppression of spontaneous motor activity suggests that fluoride has, by a central action, inhibited motivation of these animals to exhibit locomotor behavior. A cholinergic mechanism through a change in the activity of acetylcholinesterase may not account for this effect, since sodium fluoride treatment did not alter the activity this enzyme in brain regions. However, an involvement of monoamines may be proposed in view of previously reported finding that excessive fluoride intake has decreased the concentrations of 5-hydroxyindoleacetic acid and increased that of norepinephrine in rat brain.