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ABSTRACT: Amphetamines (AMP) are potent psychostimulants and commonly used drugs of abuse. Its chronic administration creates tolerance and addiction and also associated with neurotoxicity and hepatocellular damage through oxidative stress. The present study was designed to evaluate the cytotoxic effects as well as the oxidative stress induced by d-amphetamines in isolated rat hepatocytes. Hepatocytes were isolated by collagenase perfusion technique and were exposed to different concentrations of AMP (0.2, 0.4, 0.8 and 1.6mM) in a time-course experiment for up to 2h. AMP exposure induced a significant decrease in cell viability and a significant increase in the leakage of hepatic enzymes {lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and asparate aminotransferase (AST)} in a concentration and time-related manner. In the same experiment, GSH content and thiobarbituric acid reactive substances (TBARS) generation were determined as indices of oxidative stress and lipid peroxidation respectively. AMP exposure results in a significant decrease in cellular GSH content as well as a significant enhancement of TBARS accumulation in a concentration and time-related manners. The obtained results suggested that 2-h exposure of hepatocytes to AMP (0.8mM) was accompanied by submaximal responses. Therefore, a subsequent dose-response experiment was designed to evaluate the role of GSH modulation and oxidative stress in AMP toxicity in hepatocytes at 2h. LDH release and TBARS generation were used as indicators in this experiment. Pretreatment with the GSH-depleting agents, chlorodinitrobenzene (CDNB), buthionine sulfoximine (BSO), or bis(chloroethyl)-nitrosurea (BCNU) enhanced the cytotoxicity of AMP. Conversely, pretreatment with GSH or sulfhydryl compounds such as methionine (MT), cysteine (CYS) or dithiothreitol (DTT) attenuated AMP toxicity. Similarly, co-incubation with enzymatic antioxidants, superoxide dismutase (SOD) or catalase (CAT) or iron chelator, desferroxiamine (DFO) or the hydroxyl radical scavengers, dimethylsulfoxide (DMSO) exhibited significant protection against AMP cytotoxicity. The present results indicate that AMP has a potential cytotoxic effect in isolated rat hepatocytes. AMP cytotoxicity is concentration-dependent. GSH depletion and oxidative stress play an important role in enhancing hepatotoxic potential of AMP in isolated rat hepatocyte. Thiol group-donors, antioxidants, free radical scavengers and iron chelators can play a critical role against AMP-induced cellular damage.
Pathophysiology 05/2011; 18(4):279-85.
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Toxicolgest. 05/2006; 85(85: 118.).
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ABSTRACT: Vanadium is a ubiquitous trace metal present in most plant and animal tissues. Environmental exposure to trivalent and pentavalent inorganic vanadium compounds has been related to impaired different phases of reproduction. Therefore, the effects of a pentavalent inorganic vanadium compound on general reproductive performance and fertility were investigated in male and female rats. Sexually mature male and female rats were exposed to 200 ppm ammonium metavanadate in drinking water. Male rats were exposed for 70 days, while the female rats exposed for 14 days premating, during mating, and throughout the whole length of gestation and lactation periods till weaning. The effects on male sex organ weights and fertility were evaluated at the end of exposure period. However, the effects on female fertility as well as developmental and postnatal effects were evaluated throughout the exposure period. The fertility was significantly reduced in both treated groups, with more pronounced suppressive effects in the male treated group. The number of implantation sites and the number of viable fetuses were significantly reduced in pregnant females of both treated groups. However, the number of resorptions, dead fetuses, and pre- and postimplantation losses were significantly increased. The incidence of resorptions was significantly increased in treated female group compared with untreated female group. The behavioral responses as well as fetal survival and viability indices were decreased in both treated groups during the lactation period. The incidence of these effects was more pronounced in the treated female group. The morphological, visceral, and skeletal anomalies were recorded significantly increased in fetuses of both treated groups, with more pronounced effects on fetuses of treated females. In conclusion, the exposure of adult male and female rats to ammonium metavanadate would cause adverse effects on fertility and reproduction.
Pharmacological Research 02/2003; 47(1):75-85. · 4.44 Impact Factor
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J. Egypt Soc. Toxicol., 27:23-29 2002. 07/2002;
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ABSTRACT: Tributyltin oxide (TBTO) is a commonly used biocide. The purpose of this study is to correlate the toxicity of TBTO with the alterations of brain neurotransmitters and ATPases. TBTO was given by stomach tube to rats at either 37.5 or 75 mg x kg (-1)for 3 consecutive days. Nervous signs appeared in treated animals and the mortality reached 12 and 30%, respectively. The levels of brain dopamine, norepinephrine and serotonin decreased in a dose-dependent manner. The activities of brain total ATPase, Mg (2+)-ATPase and Na (+)/K (+)- ATPase were suppressed. The activity of Na (+)/K (+)- ATPase was more severely affected than that of Mg (2+)-ATPase. Histopathological changes in brain included hyperaemia, focal haemorrhages in vacuolated myelinated fibres, chromatolysis, or complete necrosis of neurons, degenerative changes, or complete absence of purkinje cells in the cerebellum.
Pharmacological Research 04/2002; 45(3):201-6. · 4.44 Impact Factor
