Zbigniew Srebro

Effects of aspirin on the levels of hydrogen sulfide and sulfane sulfur in mouse tissues

This study was designed to investigate the effect of aspirin (ASA) on anaerobic cysteine metabolism, which yields sulfane sulfur-containing compounds and hydrogen sulfide (H(2)S), in mouse liver and brain. In order to solve this problem, we determined the levels of sulfane sulfur and H(2)S, and the activities of cystathionase, the enzyme directly engaged in H(2)S synthesis, and rhodanese, the enzyme that catalyzes sulfane sulfur transfer to different acceptors. Moreover, we examined the effect of ASA on glial Gomori-positive cells (GGPC) in the brain that contain sulfur-rich glial Gomori-positive material (GGPM). The studies indicated an ASA-induced decrease in H(2)S levels in the brain and an increase in the liver. ASA-treated animals had lower cerebral levels of GGPM-containing GGPCs but the sulfane sulfur level was not affected. Conversely, the sulfane sulfur content in the liver dropped. ASA did not change cystathionase and rhodanese activity in either organ. The obtained results revealed that ASA was able to influence anaerobic cysteine metabolism, leading to the formation of sulfane sulfur and H(2)S in the mouse liver and brain, and to affect the numbers of GGPM-containing GGPCs.

The glial Gomori-positive material is sulfane sulpfur.

The Gomori-positive glia are periventricular astrocytes with abundant cytoplasmic granular material, predominantly occupying a periventricular site in the brain. These granular inclusions are strongly stained with chrome hematoxylin in the Gomoris method as well as exhibit red autofluorescence and non-enzymatic peroxidase activity. The glial Gomori-positive material (GGPM) granules are positive in the performic acid Alcian blue method indicating the presence of protein-bound sulfur, what has been shown by our previous studies. The number of cells containing glial Gomori-positive granules dropped after administration of cyanide and increased under the influence of sulfane sulfur donor (diallyl disulfide). This suggests, that sulfur of these granules is a sulfane sulfur, possibly in the form of protein-bound cysteine persulfide. Sulfane sulfur is labile, reactive sulfur atom covalently bound to another sulfur atom. In this paper we present evidence that GGPM exhibit affinity to cyanolysis and its stainability in Gomoris method is due to the presence of protein-bound sulfane sulfur. The biological role of the Gomori-positive glia connected with protective properties of sulfane sulfur has been discussed.

Lipopolysaccharide Aggravates Cerebral Pathology in B10.PL-derived CD1-/-,β2m-/-, TCRα-/-, and TCRδ-/- Knockout Mice

Adult B10.PL-derived immunological genes knockout mice injected with 100 microg lipopolysaccharide (LPS) showed severe hydrocephalus and meningitis. A consequence of the hydrocephalus is pineal hyperplasia, sponginess of periventricular parenchyma, gliosis and, at the last stage of hydrocephalus formation, disappearance of the ependymal layer and the Gomori-positive subependymal astrocytes. Possible mechanisms for the aggravation of cerebral pathology induced by LPS are discussed.

Cerebral pathology in immunodeficient gnotobiotic laboratory mice.

Gnotobiotic autoimmunity prone, antigen presentation, T lymphocyte receptor gene knockout mice show cerebral pathology in the form of meningitis, venous blood statis with subarachnoid hemorrhages and massive hemosiderin deposits. A more or less severe hydrocephalus was present in all animals examined. In all cases except the CD 1(-/-) animals, the pineal gland was considerably reduced in mass. Only in the latter strain was a strong pineal hypertrophy in the form of a benign tumor present in ca. 50% of the animals. A possible sequence of events leading to hydrocephalus is discussed. Endogenous vertically transmitted facultative pathogens, active in the immunocompromised animals, probably play a primary etiological role. The results show that caution is needed in planning immunobiological studies on the B10.PL and B10.PL-derived mice, and possibly other strains not examined for possible neuropathological changes.