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1.
Pakistan Journal of Pharmaceutical Sciences. 2018; 31 (4 [Supp.]): 1463-1467
em Inglês | IMEMR | ID: emr-199536

RESUMO

Thallium has been shown to significantly influence various tissues of living organisms; Exposure to Thallium can disturb mitochondrial function, degenerate neurons, and interfere with the function of critical metabolic enzymes and co-enzymes. Glutathione [GSH] an essential biomarker is considered a key factor in harnessing the thallium toxicity. In the present study the interaction of Thallium [Thallium Chloride] and glutathione was investigated spectro- photometrically in aqueous media. The renowned Elman's experimental protocol was followed at a wavelength of 412nm for Glutathione quantification in each sample. The pH of each sample was maintained at 7.6 using Phosphate buffer during the entire course of the experiment. A concentration as well as time dependent depletion of glutathione after exposure to various concentration of Thallium metal was observed, revealing chemical interaction between the metal and glutathione. The exact mechanism of interaction of Thallium and glutathione is still to be investigated. However, this piece of research suggests that a decrease in the concentration of Glutathione may be due to Thallium-GSH abduct or oxidize glutathione [GSSG] formation. This study was performed in-vitro as a model of in vivo

2.
Pakistan Journal of Pharmaceutical Sciences. 2018; 31 (6 Supp.): 2617-2622
em Inglês | IMEMR | ID: emr-205139

RESUMO

Ivy leaf is used for the treatment of respiratory diseases with the intensive mucus formation, respiratory infections, and irritating cough coming from the common cold. Conferring to clinical trials, the efficacy, and tolerability of ivy leaf is good. The main compounds accountable for biological activity are triterpene and saponins. Ivy leaves show convulsive/antispasmodic, anti-inflammatory, antimicrobial, analgesic, anthelmintic and anti-thrombin activity. Not only ivy but also marshmallow and mustard seeds are used for these indications. This study was conducted to evaluate the efficacy and safety of Cough [EMA; European Medicines Agency] granules used for upper respiratory disorders. This clinical trial was conducted on 150 patients, out of which 75 received the Cough [EMA] granules and 75 received the placebo. The age range of patients was 3 years to above 15 years. The sample paired t-test was applied to evaluate the significant level. Cough [EMA] granules were found effective in the treatment of cough, cold, and flu symptoms. The new treatment Cough [EMA] granules were safe and well tolerated in patient at given specific age group. The study recommends that Cough [EMA] granules can be used effectively in the treatment of upper respiratory tract infection

3.
Pakistan Journal of Pharmaceutical Sciences. 2018; 31 (1): 213-219
em Inglês | IMEMR | ID: emr-191411

RESUMO

The metalloelement Palladium has a number of potential Pharmaco-clinical advantages. Palladium compounds have antiviral, antibacterial, neuroprotective and antitumor properties. However studies have also indicated some mild to serious toxic effects of Palladium metalloelements. Biothiols are important antioxidants that provide protection against metals toxicity. The interaction of metalloelements with biothiols can provide valuable information about the level of toxicity of the metalloelements and about the protective role of biothiols thereof. In this piece of work the effect of salt and complexes of Palladium on the status of different thiols [GSH, NAC, and D-Pen] in aqueous medium, were examined, The thiol quantification was carried out using Elman's method through UV-visible spectrophotometry and 1 HNMR. Results of the study performed in aqueous medium showed that level of different thiols depleted after the addition of the inorganic salts and organic complexes of Palladium. The mechanism of interaction of Palladium with thiols was examined using H-NMR. The results indicate that the depletion in the level of thiols may be due to 1:1 or 1:2 conjugation of Palladium with thiols. These conjugation reactions further suggest that the Palladium have xenobiotic nature causing oxidative stress and thiols play their role in detoxification and biotransformation of these metalloelements

4.
Pakistan Journal of Pharmaceutical Sciences. 2018; 31 (2 Supp.): 727-731
em Inglês | IMEMR | ID: emr-195043

RESUMO

Glutathione is an essential antioxidant of living organism that provides a primary protection against metals toxicity. A significant amount of glutathione is present in blood erythrocytes, plasma and liver hepatocytes to protect them from oxidative damage from both external and internal oxidants. Metalo-element palladium has numerous pharmacological, clinical and toxicological compensations, like palladium is used as anti-viral, anti-bacterial, neuroprotective and anti-tumor agent. However studies have also indicated some mild to serious toxic effects of palladium metallo-elements. In the presence study the interaction of palladium inorganic salt and organic complex with glutathione [GSH] content of liver homogenate was examined spectro-photometrically. 20% [w/v] liver homogenate was prepared of the collected liver of rabbit in 5% TCA [tri-chloro-acetic acid] solution and 1mm EDTA, using a potter-eveljhem homogenizer with motor driven Teflon pestle. The GSH content quantification was carried out by Elman's method. Our finding showed that there was a depletion of GSH content by both palladium inorganic salts and organic complexes, concentrations wise as well as with time elapse as level of GSH content decrease from [43.6% to 72.62%] with Palladium Nitrate and from [24.09 to 59.5%] with Bis-benzonitrile Palladium II Chloride as compared to control, and further dropped with time incubation from 0-90 minutes from [49.7 to 87.1%], with Palladium Nitrate and from [29.3% to 67.6%] respectively. The result showed that the effect of both inorganic salt of palladium was more enhanced as compare to its organic complex. It was suggested from our finding that the depletion in the glutathione content of liver homogenate may be due to oxidation of glutathione or due to glutathione metal abduct formation by both inorganic salt and organic complex of palladium. This study in situ is a model of in vivo

5.
Pakistan Journal of Pharmaceutical Sciences. 2018; 31 (3 Supp.): 1067-1074
em Inglês | IMEMR | ID: emr-198718

RESUMO

Hypertension is one of cardiovascular disease that is not sufficiently prevented and controlled at both hospital and community levels. Hypertension resulted in significant morbidity and mortality. The benz-imidazole ring is very important pharmacophore in modern drug discovery. The substituted benzimidazoles are the important for medicinal research. Researchers have reported that substituted Benzimidazoles are the structural isosteres of nucleotides, and easily allow them to interact with the different biopolymers, possess pharmacological activity especially antihypertensive activity. Angiotensin II Receptor Antagonists/Blockers [ARBs] compete with angiotensin II at the receptor site and block the contractile effect of angiotensin II in all vascular smooth muscles. Among all Angiotensin II Receptor Antagonists/Blockers [ARBs], Telmisartan, Milfasartan and many others have benzimidazole ring in their structure. In this study Angiotensin II Receptor Antagonists/Blockers [ARBs] have been prepared. Synthesized compounds were characterized by physical data and FTIR spectroscopic technique. Synthesized compounds studied were finally screened for their antihypertensive activity by tail cuff method of measurement of blood pressure by NIBP apparatus [None Invasive Blood Pressure] using Chart 5.0 software. The compounds synthesized were 2-[3-nitrophenyl]-1Hbenzimidazole [1a], 3-[1H benzimidazol-2-yl]aniline [1b] and 5-[1H-benzimidazol-2-yl]-2-methoxyphenol [1c]. The synthesized compounds have shown antihypertensive activity by taking Losartan as lead compound

6.
Pakistan Journal of Pharmaceutical Sciences. 2017; 30 (6 Supp.): 2405-2410
em Inglês | IMEMR | ID: emr-190227

RESUMO

Thiol groups are extensively present across biological systems being found in range of small molecules [e.g. Glutathione, Homo-cysteine] and proteins [e.g. albumin, haemo-globin]. Albumin is considered to be a major thiol containing protein present in circulating Plasma. Albumin contains a single thiolate group located at cysteine-34[cys-34] at its active site. Albumin also binds a wide variety of metals and metals complexes at various sites around the protein. Usually heavy metals are preferentially attached with the thiol group of albumin. The binding of heavy metals at cys-34 provides a mechanism by which the residence time of potentially toxic species in the body can be increased. In this research we have assessed the oxidative modification of and metal binding capacity of cys-34 with heavy metals Palladium and Vanadium to investigate the ease with which it is possible to effect disulfide-thiol exchange at this sites/or remove a metal bound at this position. Both the metals were treated with albumin and then the albumin metals [Pd and V] complexes were treated with small thoil molecules like Glutathione, Cysteine and D-Penicillamine. Our finding showed that the albumin thiol group retained the metals with itself by forming some strong bonding with the Thiols group, it is concluded from this finding that if by chance both the metals enter the living system; strongly disturb the chemistry and physiological function of this bio-molecule

7.
Pakistan Journal of Pharmaceutical Sciences. 2015; 28 (2): 457-464
em Inglês | IMEMR | ID: emr-178141

RESUMO

Arsenic is a major threat to large part of the population due to its carcinogenic nature. The toxicity of Arsenic varies with its chemical form and oxidation states. Glutathione [GSH], a major intra-cellular tripeptide plays a major role in arsenic detoxification. The present study was designed to provide insight into the extent of changes in GSH level by inorganic arsenic in the form of Arsenic trioxide [ATO] and organic arsenic in the form of nitro benzene arsenic acid [NBA]. Lymphocytes [T.cells and B.cells] were investigated for determination of change in GSH metabolic status caused by arsenic. The depletion of GSH level positively correlated with increasing arsenic concentration and time of incubation. The decline in GSH level was consistent with increasing pH and physiological temperature. Our findings show that changes in GSH status produced by Arsenic could be due to adduct [As-[SG][3]] formation. This change in GSH metabolic status provides information regarding mechanism of toxicity of inorganic and organic arsenicals. These findings are important for the rational design of antidote for the prevention of arsenic induced toxicity


Assuntos
Humanos , Glutationa , Linfócitos T , Linfócitos B , Arsenicais , Óxidos , Nitrobenzenos
8.
Pakistan Journal of Pharmaceutical Sciences. 2013; 26 (1): 131-135
em Inglês | IMEMR | ID: emr-146758

RESUMO

This piece of research work present the toxicological impact of varied concentrations of Palladium Nitrate [Pd [NO[3][2] by changing the chemical status of glutathione and the way how glutathione plays its role in detoxification and conjugation processes of [Pd [NO[3][2] in whole blood components [plasma and Cytosolic fraction]. The impact of different concentration of [Pd [N03]2] on reduced glutathione level in whole blood component [Plasma and Cytosolic fraction] were measured spectrophotometrically following Standard Ellman's method. Compared with control sample, significant decrease in the GSH content in whole blood components [plasma and Cytosolic fraction] was obtained with various concentrations [100microM-1000microM] of Palladium Nitrate. Depleted GSH level was more pronounced with time incubation period [0-90] minutes. These finding shows that changes in the GSH status produced by palladium nitrate could either be due to palladium nitrate and glutathione [Pd-SG] complex formation or by conversion of reduce glutathione [2GSH + Pd[+2] -> GSSG]. This change in the GSH metabolic status provides information regarding the mechanism of palladium, in blood components


Assuntos
Paládio
9.
Pakistan Journal of Pharmaceutical Sciences. 2012; 25 (2): 395-400
em Inglês | IMEMR | ID: emr-128896

RESUMO

Mercury is harmless in an insoluble form, such as mercuric sulfide, but it is poisonous in soluble forms such as mercuric chloride or methylmercury. Mercury is a neurotoxin. Outbreaks of mercuric chloride poisonings have made it clear that adults, children, and developing fetuses are at risk from ingestion exposure to mercury. It is very important and interesting to study the reaction of mercuric chloride and Glutathione as biomarker of Glutathione role in detoxification and conjugation in components [Plasma and Cytosolic Fraction]. The effect of mercuric chloride's different concentrations was examined on GSH present in plasma and cytosolic fraction. Decrease in GSH level was dependant on mercuric chloride concentration. The decrease in GSH level of blood components was more prominent with the time of incubation of mercuric chloride. Decrease in the concentration of reduced state Glutathione may be due the interaction of reduced state Glutathione [GSH] and mercuric chloride to form oxidized Glutathione [GSSG] or mercuric-glutathione complex. This change in GSH metabolic status provides information regarding the role of GSH in detoxification of mercuric chloride. The effect of mercury metal on Glutathione in blood components has been discussed in this paper in vitro condition as a model for in Vivo condition


Assuntos
Humanos , Intoxicação por Mercúrio/prevenção & controle , Mercúrio/toxicidade , Compostos de Mercúrio/toxicidade , Ácido Ditionitrobenzoico
10.
Pakistan Journal of Pharmaceutical Sciences. 2012; 25 (3): 549-553
em Inglês | IMEMR | ID: emr-144404

RESUMO

Metallo-elements including Vanadium [V] have strong affinity for sulfhydryl [-SH] groups in biological molecules including Glutathione [GSH] in tissues. Because of this fact it was of interest to further investigate the interaction of Ammonium Vanadate [NH[4]VO[3]] with Glutathione as a biomarker of toxicity and the role of Glutathione in the detoxification and conjugation processes in whole blood components including plasma and cytosolic fraction. Effects of different concentrations of Ammonium Vanadate [NH[4]VO[3]] on the level of reduced Glutathione in whole blood components [Plasma and Cytosolic fraction] were examined. GSH depletion in plasma and cytosolic fraction was Ammonium Vanadate's concentration-dependent. Depleted GSH level was more pronounced with more incubation time period. These findings show that changes in the GSH status produced by Ammonium Vanadate could be due to either by adduct formation of Vanadium and glutathione i.e. [V-SG] or by increased production of oxidized Glutathione [2GSH +V[+5] - GSSG]. This change in GSH metabolic status provides some information regarding the mechanism of toxicity by Ammonium Vanadate and the protective role of glutathione


Assuntos
Humanos , Glutationa/sangue , Vanadatos/metabolismo , Dissulfeto de Glutationa/metabolismo , Biomarcadores/sangue , Citosol/metabolismo , Relação Dose-Resposta a Droga
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