Light and electron microscope examination of the effects of methotrexate on the endosalpinx

WOS: 000229276900016PubMed: 15866094Objective: To examine the effects of increasing doses of methotrexate (Mtx) on the fallopian tubes. Study design: The study was carried out on 24 female rats (Albino Wistar type, 250-300 g). The rats were randomly divided into four groups of six. Different doses of Mtx were given to the rats by i.p. injection: 1 mg/kg to those in group 1, 5 mg/kg in group 2 and 10 mg/kg in group 3. Rats in group 4 received injections of physiological serum only and were treated as the control group. Ten days after the injection, the fallopian tubes of the rats were removed for examination separately by light and electron microscopy (EM) for comparison. Results: Light microscopy showed that in group I the surface epithelial cells were normal and the lamina propria was infiltrated by numerous inflammatory cells with a prevalence of polymorphonuclear leucocytes. Findings in groups 2 and 3 were similar: the lamina propria was infiltrated with granulocytes in one specimen from each of the two groups, and granulocytes were also observed among epithelial cells. In the control group all surface structures were found to be in a normal condition. Electron microscopy showed cilial loss in the epithelial cells and central crystolysis in mitochondria in all group I specimens. Findings in groups 2 and 3 were similar. The cytoplasm of the epithelial cells seemed to be dense, there was prominent crystolysis (crystalloid formation) in the mitochondria, and vacuolisation (vacuole formation) in the cytoplasm seemed to be augmented. Cilial loss was prominent, and the basal membrane was irregular. Epithelial cell nuclei were in disorder. Lipid granules were observed extensively in epithelial cells. Eosinophils seemed to be dominant in connective tissues below the epithelium. In all control group specimens the epithelium seemed to be normal with all organelles in place; the condition of intercellular junctions, ciliated epithelium and all mitochondria also seemed to be normal, and the basal membrane was observed to be in order. Conclusion: In view of these findings, we conclude that the ultrastructural derangements resulting from administration of Mtx in doses in excess of I mg/kg can cause a reduction in the surface epithelium's ability to make rhythmic lashing movements and can impair the patency of the fallopian tubes. All these disturbances could be involved to some degree in the causation of infertility and recurrent ectopic pregnancy. Therefore, the dosage of Mtx should be limited to use of the lowest effective dose to avoid these adverse effects. (c) 2004 Elsevier Ireland Ltd. All rights reserved

Effects of amifostine on glycerol-pretreated rabbit kidneys

Glycerol-induced acute renal failure is an experimental model for myoglobinuric nephropathy. Amifostine is a cytoprotective agent which scavenges the free radicals. Since there is enhanced production of reactive oxygen metabolites in glycerol-induced acute renal failure, we wanted to examine whether amifostine has a protective role against vascular reactivity and histological changes in kidneys isolated from glycerol-pretreated rabbits. Perfusion pressure was recorded from kidneys obtained from rabbits injected with glycerol 3 hr before the experiments and from glycerol-pretreated and non-pretreated rabbits injected with amifostine 30 min. before the experiments. Acetylcholine-induced (10(-8)-10(-5) M) vasodilatation was tested following the construction of submaximal vasoconstriction by phenylephrine. Histological investigation was performed using light microscope. Acetylcholine-induced vasodilatation was found to be significantly decreased in glycerol, glycerol+ amifostine and amifostine groups compared to controls at all concentrations. Reduction in acetylcholine-induced vasodilation was more prominent in arnifostine group compared to arnifostine +glycerol group. There was histological renal damage in all experimental groups and this damage was more pronounced in glycerol +amifostine group. In conclusion, contrary to expectation, arnifostine per se led to histological damage and potentiated the histological damage caused by glycerol and produced a decrease in acetylcholine-induced vasodilatation. The mechanisms by which arnifostine exerts its effects are not known