ABSTRACT: The current study was undertaken to investigate the protective role of melatonin (MEL) and acetyl-L-carnitine (ALC) against dexamethasone (DM)-induced neurotoxicity. Adult female rats (60) were divided into: (1) control group, (2) DM-treated group, (3) MEL-treated group, (4) ALC-treated group, (5) MEL- and DM-treated, and (6) ALC- and DM-treated group. Serum acetylcholinesterase (AchE) activity, malondialdehyde (MDA), nitric oxide (NO) level, catalase (CAT), superoxide dismutase (SOD) and glutathione-S-transferase (GST) activities were estimated. Gene expression of the prooxidants (NO synthases NOS-1, NOS-2 and heme oxygenases HO-1, HO-2) and antioxidant enzyme (GST-P1) as well as deoxyribonucleic acid (DNA) fragmentation analysis of brain tissue were investigated. Histological examination of the brain tissue was carried out. DM administration caused significant increase in serum AchE activity, MDA and NO levels accompanied with significant decrease in the antioxidant enzymes activity. Pretreatment with MEL or ALC prior DM has been found to reverse all the former parameters. On the genetic level, DM administration significantly increased the expression level of NOS-1, NOS-2, HO-1, and HO-2 messenger ribonucleic acids (mRNAs) and decreased that GST-P1-mRNA in brain tissue. Also, DM produced DNA fragmentation in brain tissue. Treatment with MEL or ALC prior DM administration tend to normalize the above mentioned parameters. These results were documented by the histological examination of brain tissue. The present study suggests that oxidative stress is involved in the pathogenesis of DM-induced neurotoxicity. The inhibition of oxidative stress via stimulation of the antioxidant enzymes by MEL and ALC pretreatment plays a central protective role in modulation of neurotoxicity induced by DM.
Journal of physiology and biochemistry 03/2012; 68(1):77-90. · 1.71 Impact Factor
ABSTRACT: Dibromoacetonitrile (DBAN) is water disinfectant by-product. Its broad-spectrum toxicity in different test systems in vivo and in vitro has been reported. However, there is a scanty of information regarding dibromoacetonitrile hepatotoxicity. Therefore, this study aimed to investigate the possible mechanisms for dibromoacetonitrile-induced tumor initiation in rat liver cells. Dibromoacetonitrile was orally administered to rats as an acute (60 mg/kg) and fractionated (7.5mg/kg) doses, weekly twice for 4 weeks and once weekly for 8 weeks. Significant increase in malondialdehyde level (approximately 7-, 6- and 4-folds) and extensive depletion in total antioxidant capacity were detected following acute and fractionated doses respectively. Alanine aminotransferase (about 2- and 1-folds) and aspartate aminotransferase (3- and 2-folds) were significantly increased after acute dose and fractionated doses for 4 weeks. Also, these doses of dibromoacetonitrile produced high levels of DNA fragmentation, micronucleated polychromatic erythrocytes and changes in the expression of hepatocyte growth factor gene and proto-oncogenes (c-met and c-myc) in liver tissues. Ability of dibromoacetonitrile to induce DNA damage and alterations in the expression of tumor-initiating genes was suggested to be due to hepatotoxicity, oxidative stress and disturbance in the oxidant/antioxidant status of rat liver.
Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 12/2011; 49(12):3055-62. · 2.99 Impact Factor
ABSTRACT: Cisplatin (CP), a broadly used anticancer drug, is widely known to induce acute renal failure as a result of renal tubular injury.
In this study, the effect of N-acetyl cysteine (NAC) or taurine (TAU) for protection against CP-induced nephrotoxicity was investigated.
A single dose of CP 1 mg/kg b.wt. for 4 days was given IP to the rats, 10 days rest, and then the dose was repeated for other 4 days. After CP administration, NAC or TAU was given IP in a dose of 50 mg/kg b.wt. 3 times weekly for 8 weeks.
CP-induced nephrotoxicity is reflected in high values of blood urea and creatinine levels. In addition, the significant increase in the β(2)-MG and N-acetyl-β-glucosaminidase enzymes exhibited a strong correlation with histology scores of overall proximal tubule damage as compared with the normal control values. Treatment with TAU or NAC after CP administration significantly ameliorated CP-induced nephritic oxidation stress markers as compared with CP-treated group. On the other hand, treatment with TAU or NAC after CP administration significantly ameliorated CP-induced nephritic inflammation with possible attenuation of renal injury.
These data suggest that oxidative stress and inflammation are involved in the pathogenesis of CP-induced acute renal failure. The inhibition in oxidative stress and the elevation of the total antioxidant capacity as well as the inhibition of the inflammatory biomarkers by NAC or TAU after CP administration may play a central role in modulation of nephrotoxicity induced by CP.
NAC and TAU have antioxidant and anti-inflammatory against CP-induced nephrotoxicity.
Toxicology mechanisms and methods 04/2011; 21(7):538-46. · 1.03 Impact Factor