Piroxicam-induced hepatic and renal histopathological changes in mice

Piroxicam is a non-steroidal anti-inflammatory drug widely used in rheumatic diseases. The aim of this study was to investigate Piroxicam-induced histopathological changes in livers and kidneys of male albino mice. Animals were classified into a control group and 4 treated groups. Piroxicam was injected intraperitoneally using 0.3 mg/kg every day for four weeks. Each week a group of mice was sacrificed. Liver and kidneys were obtained for histological and histochemical examination. Animals were classified into a control group and 4 treated groups. Piroxicam was injected intraperitoneally using 0.3 mg/kg every day for four weeks. Each week a group of mice was sacrificed. Liver and kidneys were obtained for histological and histochemical examination. Liver sections appeared with inflammatory cellular infiltration, vacuolated hepatocytes, dilated sinusoids, and increased number of Kupffer cells. Kidney sections appeared with some cellular inflammations. The glomeruli were shrunk resulting in widening of the urinary space. Oedema and vacuolations were noticed in the tubular cells. There was a positive correlation between these pathological changes and the increased treatment periods. Histochemical staining revealed that glycogen and protein contents had decreased in the hepatocytes. This depletion worsened gradually in liver cells after two, three, and four weeks. Similar depletion of the glycogen content was observed in kidney tissue. However, protein content appeared to be slightly decreased in the kidney tubules and glomeruli. Incensement of coarse chromatin in the nuclei of hepatocytes, Kupffer cells and most inflammatory cells were detected by Fuelgen method. Kidney tissues appeared with a severe decrease in coarse chromatin in the nuclei. Liver sections appeared with inflammatory cellular infiltration, vacuolated hepatocytes, dilated sinusoids, and increased number of Kupffer cells. Kidney sections appeared with some cellular inflammations. The glomeruli were shrunk resulting in widening of the urinary space. Oedema and vacuolations were noticed in the tubular cells. There was a positive correlation between these pathological changes and the increased treatment periods. Histochemical staining revealed that glycogen and protein contents had decreased in the hepatocytes. This depletion worsened gradually in liver cells after two, three, and four weeks. Similar depletion of the glycogen content was observed in kidney tissue. However, protein content appeared to be slightly decreased in the kidney tubules and glomeruli. Incensement of coarse chromatin in the nuclei of hepatocytes, Kupffer cells and most inflammatory cells were detected by Fuelgen method. Kidney tissues appeared with a severe decrease in coarse chromatin in the nuclei. Piroxicam has a time-dependent toxic effect on both liver and kidney tissues

Do molecular markers predict the electromagnetic field treatment of cancer through p53 suppressor gene?

In recent years there have been enormous studies made toward understanding diagnosis and treatment of cancer. Although there has been a great deal learned about cancer, the treatments available for it have not progressed nearly as much. Attempted removal of the tumor followed by chemotherapy and radiotherapy still prevail as the most effective treatments used. The present study used the electromagnetic fields [4.5 Hz] to treat tumor implanted in mice. The Polymerase Chain Reaction/Restriction Fragment Length Polymorphisms [PCR/RFLPs] technique was selected as a biomarker to evaluate the effect of exposure to electromagnetic fields in implanted Ehrlich tumor of female BALB/C mice. Eighty mice used and divided into four groups [20 each]; control, radiated [control exposed to 4.5 Hz], infected [control infected by Ehrlich tumor] and infected exposed [infected exposed to 4.5 Hz]. The duration of exposure was for two hours every two days. Electromagnetic field exposure includes group 2 and group 4. DNA genome was extracted and p53 suppressor gene detected [tilde 2130 bp]. AatI, BanII, EaeI restriction endonucleases did not differentiate between the PCR products [p53 genes] of the four groups [control, radiated, infected and infected exposed mice groups]. BanI, DraI, DraIII, HaeII and PstI differentiated between the four groups. The results approved that the electromagnetic fields could treat the tumor and PCR/RFLPs could be useful diagnostic technique

Genotoxicity induced by drug-drug interaction between the antidepressant sertraline and the antibiotic erythromycin in mice bone marrow cells

Drug-drug interaction represents a widely distributed health problem. The pharmacological action and side effects of two or more drugs can act additively or antagonistically. The present study was designed to evaluate the possible genotoxicity of concurrent treatment with the antidepressant sertraline, one of the serotonin reuptake inhibitors [SSRI] and the broad spectrum macrolide antibiotic erythromycin. Sertraline and erythromycin are metabolized through CYP3A4 which is one of the cytochrome P-450 enzymes in liver and are responsible for the metabolism of large number of endogenous substrates and therapeutic agents. The frequency of micronucleated polychromatic erythrocytes [MNPCEs], micronucleated normochromatic erythrocytes [MNNCEs] and the ratio PCE/NCE were evaluated to measure the genotoxicity of separate and combined treatment with the tested two drugs. Clinical doses of both sertraline [0.71 mg /kg b.w.] and erythromcyin strearate [14.30 mg / kg b.w.] were used. Groups of animals received single separate or combined doses of either sertraline and/or erythromycin, and sacrificed after 24 hours. Other groups of mice were treated in the same way but for five consecutive days and sacrificed 24 hours after the last injection. In all treated groups, the percentage of PCEs increased significantly when compared with that of the negative control group which may indicate a stimulation of proliferative activity to an early phase of cell depletion. The genotoxicity of multiple treatment for 5 consecutive days with sertraline alone or in combination with erythromcyin was expressed in increased number of MNPCEs. The observed increased genotoxicity after multiple combined treatment with sertraline and erythromycin may indicate increased risk of toxicity-based drug-drug interaction. This toxicity may be due to the ability of sertraline and erythromycin to inhibit the activity of CYP3A4 which lead to a prolonged storage period of drugs in the body and hence increased toxicity

Molecular biological studies on the effect of the electromagnetic fields on ETS-1 oncogene

ETS-1 is the founding member of the ETS family of transcription factors. ETS factors have important roles in oncogenesis, signal transduction and development. In human tumors, ETS-1 is expressed in endothelial cells and fibroblasts of the tumor stroma and is proposed to play a role in tumor vascularization and invasion by upregulating expression of matrix-degrading proteases. In human carcinomas, ETS-1 is also expressed by neoplastic cells, but little is known about the functional implications of this observation. The present study aimed to detect the tumor by using electromagnetic fields through ETS-1 oncogene. The detection of point mutations correlated with diseases is currently performed by digestion of PCR products [PCR/RFLP] by using restriction endonucleases. It has been described here a method based modified on primers during the PCR, and using some restriction endonucleases [AatI, BanI, BanII, DraI, DraIII, EaeI, PstI and SacII] which create a restriction fragment length polymorphism [RFLP] indicative of the studied mutation. The present study used the electromagnetic fields [4.5 Hz]; PCR/RFLPs technique was selected as a biomarker to evaluate the effect of exposure to electromagnetic fields in implanted Ehrlich tumor of female BALB/C mice. Eighty mice were used and divided into four groups [20 each]; normal, exposed [exposed to 4.5 Hz], infected [normal infected by Ehrlich tumor] and infected exposed [infected exposed to 4.5 Hz]. DNA genome was extracted and ETS-1 oncogene detected [tilde 4460 bp]. AatI, BanII and EaeI restriction endonucleases did not differentiate between the PCR products [ETS-1 genes] of the four groups [normal, exposed, infected and infected exposed mice groups]. DraIII, SacII, PstI, BanI and DraI differentiated between the four groups. The results proved that the electromagnetic fields could treat the tumor and PCR/RFLPs were able to be a useful diagnostic technique