Biomedical subjects

Daniel L Morgan

Publications and source records attributed to Daniel L Morgan.

23 records · Page 2Linked to original sources

PubMed2003

Vitamin C, glutathione, or lipoic acid did not decrease brain or kidney mercury in rats exposed to mercury vapor.

UNLABELLED: Some medical practitioners prescribe GSH and vitamin C alone or in combination with DMPS or DMSA for patients with mercury exposure that is primarily due to the mercury vapor emitted by dental amalgams. HYPOTHESIS: This study tested the hypothesis that GSH, vitamin C, or lipoic acid alone or in combination with DMPS or DMSA would decrease brain mercury. METHODS: Young rats were exposed to elemental mercury by individual nose cone, at the rate of 4.0 mg mercury per m3 air for 2 h per day for 7 consecutive days. After a 7-day equilibrium period, DMPS, DMSA, GSH, vitamin C, lipoic acid alone, or in combination was administered for 7 days and the brain and kidneys of the animals removed and analyzed for mercury by cold vapor atomic absorption. RESULTS: None of these regimens reduced the mercury content of the brain. Although DMPS or DMSA was effective in reducing kidney mercury concentrations, GSH, vitamin C, lipoic acid alone, or in combination were not. CONCLUSION: One must conclude that the palliative effect, if any, of GSH, vitamin C, or lipoic acid for treatment of mercury toxicity due to mercury vapor exposure does not involve mercury mobilization from the brain and kidney.

Administration, Inhalation↗

PubMed2002

Effect of mercury vapor exposure on metallothionein and glutathione s-transferase gene expression in the kidney of nonpregnant, pregnant, and neonatal rats.

Elemental mercury (Hg(0)) is a ubiquitous toxic pollutant. Exposure to Hg(0) vapor typically is by inhalation, and the kidney is the primary target organ. Glutathione (GSH) and metallothionein (MT) appear to mitigate mercury toxicity. However, little is known about GSH or MT regulation after Hg(0) vapor exposure, particularly during pregnancy, a time of high sensitivity to most metals. Thus, this study sought to determine renal mercury accumulation and MT- and GSH-related gene expression following Hg(0) vapor exposure in nonpregnant, pregnant, and neonatal rats exposed in utero. Groups (n = 5) of pregnant rats (Long-Evans) were exposed to Hg(0) vapor (4 mg/m(3)) or air (control) for 2 h/d from gestational day (GD) 6 to 15, and kidneys from dams and pups were removed at various times during and after the onset of exposure. For comparative purposes, nonpregnant female rats were exposed to Hg(0) for 10 d under the same conditions. Renal mercury, MT protein, and GST activity were assayed by standard analytical techniques. Western blot analysis was also performed using antibodies against MT and GST-pi. GSH-related gene expression was studied by cDNA microarray. Hg(0) vapor exposure produced renal accumulation of mercury in nonpregnant, pregnant, and neonatal rats. However, the transplacentally exposed neonates accumulated approximately 1000-fold less mercury than adults. Hg(0) vapor exposure produced a time-dependent increase in renal MT protein in nonpregnant and pregnant rats, but not in neonatal rats. Maximum MT increases were observed on d 10 (fivefold) in nonpregnant and GD 15 (threefold) in pregnant rats. Activation of the MT gene by Hg(0) was confirmed at the translational level by Western blot analysis and at the transcriptional level by Northern blot analysis. Microarray analysis revealed a significant upregulation in the renal expression of the GST-pi, GST-Ya, and microsomal GST and GST5-5 genes in nonpregnant and pregnant rats. Western blot and enzyme assay confirmed the upregulation of GST genes after Hg(0) exposure. Thus, in response to Hg(0) vapor exposure, the expression of the MT gene and various GST genes is activated in nonpregnant and pregnant rats. Activation of these genes could be part of a defensive response directed at decreasing renal mercury toxicity, and may help divert the metal away from the fetus.

Administration, Inhalation↗

PubMed2002

Susceptibility of cyclooxygenase-2-deficient mice to pulmonary fibrogenesis.

The cyclooxygenase (COX)-2 enzyme has been implicated as an important mediator of pulmonary fibrosis. In this study, the lung fibrotic responses were investigated in COX-1 or COX-2-deficient (-/-) mice following vanadium pentoxide (V(2)O(5)) exposure. Lung histology was normal in saline-instilled wild-type and COX-deficient mice. COX-2(-/-), but not COX-1(-/-) or wild-type mice, exhibited severe inflammatory responses by 3 days following V(2)O(5) exposure and developed pulmonary fibrosis 2 weeks post-V(2)O(5) exposure. Western blot analysis and immunohistochemistry showed that COX-1 protein was present in type 2 epithelial cells, bronchial epithelial cells, and airway smooth muscle cells of saline or V(2)O(5)-exposed wild-type and COX-2(-/-) mice. COX-2 protein was present in Clara cells of wild-type and COX-1(-/-) terminal bronchioles and was strongly induced 24 hours after V(2)O(5) exposure. Prostaglandin (PG) E(2) levels in the bronchoalveolar lavage (BAL) fluid from wild-type and COX-1(-/-) mice were significantly up-regulated by V(2)O(5) exposure within 24 hours, whereas PGE(2) was not up-regulated in COX-2(-/-) BAL fluid. Tumor necrosis factor-alpha was elevated in the BAL fluid from all genotypes after V(2)O(5) exposure, but was significantly and chronically elevated in the BAL fluid from COX-2(-/-) mice above wild-type or COX-1(-/-) mice. These findings indicate that the COX-2 enzyme is protective against pulmonary fibrogenesis, and we suggest that COX-2 generation of PGE(2) is an important factor in resolving inflammation.

Animals↗

PubMedDate not supplied

Effects of mercury vapor inhalation on reactive oxygen species and antioxidant enzymes in rat brain and kidney are minimal.

Metals are known to induce the formation of reactive oxygen species (ROS) that initiate oxidative stress, an important mechanism of cell injury. The brain is particularly sensitive to oxidative attack because of its high level of unsaturated lipids and high rate of oxidative metabolism. The objective of this study was to determine if elemental mercury (Hg(0)) vapor inhalation increases ROS production and affects activities or levels of antioxidant-related biomolecules in the rat brain and kidney. Adult female Sprague-Dawley rats were exposed for 2 h per day for 11 consecutive days to Hg(0) vapor (1, 2, and 4 mg Hg(0) m(-3)). Brain regions (frontal cortex, cerebellum, brain stem) and kidney were assayed for total Hg, ROS and glutathione (GSH) levels, and for enzyme activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD). Marked exposure-related increases (2500-5600-fold) in total Hg were detected in the brain regions and in kidney. A statistically significant increase in ROS production (ca. 30% above controls) was observed only in the cortex of rats exposed to 1 mg m(-3) Hg vapor, but no significant changes were apparent at other exposures. Although a trend towards increasing ROS production was observed in the kidney, these effects were not statistically significant. Mercury vapor exposure had no significant effects on GSH levels or GPx activity in the three brain regions, however, statistically significant decreases in GSH and GPx activity were detected in the kidneys of rats exposed to 2 mg m(-3). Mercury exposure did not cause significant effects on SOD activity in the brain or kidney. The data indicate that oxidative stress and changes in GSH and activities of antioxidant enzymes do not play a major role in Hg(0) vapor toxicity in brain and kidney.

Administration, Inhalation↗

PubMedDate not supplied

Contribution of magnetic resonance microscopy in the 12-week neurotoxicity evaluation of carbonyl sulfide in Fischer 344 rats.

In this carbonyl sulfide (COS) study, magnetic resonance microscopy (MRM) and detailed light microscopic evaluation effectively functioned in parallel to assure that the distribution and degree of pathology in the brain was accurately represented. MRM is a powerful imaging modality that allows for excellent identification of neuroanatomical structures coupled with the ability to acquire 200 or more cross-sectional images of the brain, and the ability to display them in multiple planes. F344 rats were exposed to 200-600 ppm COS for up to 12 weeks. Prior to MRM, rats were anesthetized and cardiac perfused with McDowell Trump's fixative containing a gadolinium MR contrast medium. Fixed specimens were scanned at the Duke Center for In Vivo Microscopy on a 9.4 Tesla magnetic resonance system adapted explicitly for microscopic imaging. An advantage of MRM in this study was the ability to identify lesions in rats that appeared clinically normal prior to sacrifice and the opportunity to identify lesions in areas of the brain which would not be included in conventional studies. Other advantages include the ability to examine the brain in multiple planes (transverse, dorsal, sagittal) and obtain and save the MRM images in a digital format that allows for postexperimental data processing and manipulation. MRM images were correlated with neuroanatomical and neuropathological findings. All suspected MRM images were compared to corresponding H&E slides. An important aspect of this study was that MRM was critical in defining our strategy for sectioning the brain, and for designing mechanistic studies (cytochrome oxidase evaluations) and functional assessments (electrophysiology studies) on specifically targeted anatomical sites following COS exposure.

Administration, Inhalation↗