Biomedical subjects

P J Vuchetich

Publications and source records attributed to P J Vuchetich.

6 recordsLinked to original sources

PubMed1999

Rhodesian trypanosomiasis in a splenectomized patient.

We report the first apparent case of a splenectomized individual who developed severe trypanosomiasis with central nervous system involvement. The patient was a 41-year-old man who participated in an east African safari. Upon his return to the United States, the patient presented with an infection with Trypanosoma brucei rhodesiense that was treated successfully with suramin and melarsoprol. The onset of symptoms, laboratory studies, and disease progression did not differ from previously reported cases in the literature. The role of the spleen in trypanosomiasis is not well understood and the few reports available describe only animal models. This report suggests that asplenia had no apparent effect on the onset of symptoms and overall severity of illness. Further studies are necessary to ultimately define the role of the spleen in trypanosomiasis.

Adult↗

PubMed1998

Protective effects of zinc salts on TPA-induced hepatic and brain lipid peroxidation, glutathione depletion, DNA damage and peritoneal macrophage activation in mice.

1. The comparative protective abilities of zinc L-methionine, zinc DL-methionine, zinc sulfate, zinc gluconate, L-methionine, DL-methionine, and vitamin E succinate (VES) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced lipid peroxidation, DNA fragmentation, and glutathione depletion in the hepatic and brain tissues, and production of reactive oxygen species by peritoneal macrophages were assessed. In addition, mice were fed a zinc-deficient diet for 5 weeks, and treated with TPA and/or zinc L-methionine or zinc DL-methionine, and similar studies were conducted. 2. The zinc-deficient diet induced oxidative stress in the hepatic and brain tissues as well as in the peritoneal macrophages as evidenced by significantly enhanced lipid peroxidation. DNA fragmentation, glutathione depletion, and production of reactive oxygen species. 3. Treatment of mice with zinc L-methionine, zinc DL-methionine, and VES decreased TPA-induced reactive oxygen species production as evidenced by significant decreases in chemiluminescence in peritoneal macrophages by approximately 45%, 31%, and 47%, respectively, and cytochrome c reduction by approximately 54%, 35%, and 41%, respectively, as compared with control values. Similar results were observed with liver and brain lipid peroxidation, DNA fragmentation, and glutathione depletion. 4. Zinc salts and antioxidants provided significant protection against TPA-induced oxidative damage. Zinc L-methionine provided the best protection.

Animals↗

PubMed1998

Induction of oxidative stress and DNA damage by chronic administration of naphthalene to rats.

Naphthalene is a bicyclic aromatic compound that is widely used in various domestic and commercial applications including lavatory scent disks, soil fumigants and moth balls. Little information is available regarding the mechanism of naphthalene toxicity. We have assessed the oral, low dose (0.05 LD50) chronic effects of naphthalene (110 mg/kg/day p.o. in corn oil) for 120 consecutive days on lipid peroxidation and DNA fragmentation in the liver and brain tissues of female Sprague-Dawley rats. The animals were sacrificed on 0, 15, 30, 45, 60, 75, 90, 105 and 120 days of treatment. Maximum increases in hepatic and brain lipid peroxidation and DNA fragmentation were observed between 90 and 105 days of treatment. Following administration of naphthalene for 90 days, approximately 1.4- and 1.3-fold increases in lipid peroxidation were observed in the hepatic and brain tissues, respectively, while under the same conditions and time points 1.9- and 2.5-fold increases in hepatic and brain DNA fragmentation were observed, respectively. These results demonstrate that low dose chronic administration of naphthalene induces an oxidative stress resulting in tissue damaging effects that may contribute to the toxicity and carcinogenicity of naphthalene.

Administration, Oral↗

PubMed1997

Induction of oxidative stress by chronic administration of sodium dichromate [chromium VI] and cadmium chloride [cadmium II] to rats.

Recent studies have demonstrated that both chromium (VI) and cadmium (II) induce an oxidative stress, as determined by increased hepatic lipid peroxidation, hepatic glutathione depletion, hepatic nuclear DNA damage, and excretion of urinary lipid metabolites. However, whether chronic exposure to low levels of Cr(VI) and Cd(II) will produce an oxidative stress is not shown. The effects of oral, low (0.05 LD50) doses of sodium dichromate [Cr(VI); 2.5 mg/kg/d] and cadmium chloride [Cd(II); 4.4 mg/kg/d] in water on hepatic and brain mitochondrial and microsomal lipid peroxidation, excretion of urinary lipid metabolites including malondialdehyde, formaldehyde, acetaldehyde and acetone, and hepatic nuclear DNA-single strand breaks (SSB) were examined in female Sprague-Dawley rats over a period of 120 d. The animals were treated daily using an intragastric feeding needle. Maximum increases in hepatic and brain lipid peroxidation were observed between 60 and 75 d of treatment with both cations. Following Cr(VI) administration for 75 d, maximum increases in the urinary excretion of malondialdehyde, formaldehyde, acetaldehyde, and acetone were 2.1-, 1.8-, 2.1-, and 2.1-fold, respectively, while under the same conditions involving Cd(II) administration approximately 1.8-, 1.5-, 1.9-, and 1.5-fold increases were observed, respectively, as compared to control values. Following administration of Cr(VI) and Cd(II) for 75 d, approximately 2.4- and 3.8-fold increases in hepatic nuclear DNA-SSB were observed, respectively, while approximately 1.3- and 2.0-fold increases in brain nuclear DNA-SSB were observed, respectively. The results clearly indicate that low dose chronic administration of sodium dichromate and cadmium chloride induces an oxidative stress resulting in tissue damaging effects that may contribute to the toxicity and carcinogenicity of these two cations.

Acetaldehyde↗

PubMed1997

Protection against chemically-induced oxidative gastrointestinal tissue injury in rats by bismuth salts.

Oxygen free radicals (OFR) are implicated in the pathogenesis of stress, chemically induced gastric lesions, and gastrointestinal injury. The concentration-dependent scavenging abilities of bismuth subsalicylate (SBS), colloidal bismuth subcitrate (CBS), and selected OFR scavengers, including superoxide dismutase (SOD), catalase, mannitol, and allopurinol were examined against biochemically or chemically generated superoxide anion, hydroxyl radical, and hypochlorite radical plus hypochlorous acid based on a chemiluminescence assay. Furthermore, both gastric (GM) and intestinal mucosa (IM) were individually exposed in vitro to these free radical generating systems, and the concentration-dependent protective abilities of SBS and CBS against lipid peroxidation (LP) were compared with selected OFR scavengers. In addition, 24-hr fasted rats were orally treated with the necrotizing agents 0.6 M HCl, 0.2 M NaOH, 80% ethanol, and aspirin (200 mg/kg). The extent of tissue injury in the GM and IM was determined by assessing LP, DNA fragmentation, and membrane microviscosity. Dose- and time-dependent in vivo protective abilities of CBS (100 mg/kg) and SBS (15 mg/kg) were also assessed. Following incubations with superoxide anion and hydroxyl radical generating systems in the presence of 125 mg SBS/liter, approximately 47% and 61% inhibitions were observed in the chemiluminescence response, respectively, while 48% and 46% inhibitions were observed with 125 mg CBS/liter. SBS and CBS exerted similar abilities towards hypochlorite radical plus hypochlorous acid. Approx. 3.1- and 3.7-fold increases in LP were observed in the GM and IM of rats following oral administration of 0.6 M HCl. Pretreatment of the rats with SBS and CBS decreased 0.6 M HCl-induced LP in the GM by approx. 39% and 27%, respectively, with similar decreases in LP in the IM. SBS exhibited better protective abilities towards 0.6 M HCl and 0.2 m NaOH-induced GM and IM injury as compared to CBS. SBS and CBS provided similar protection towards 80% ethanol-induced gastric injury, while CBS exerted a superior protective ability towards aspirin-induced gastric injury. The results demonstrate that both SBS and CBS can scavenge reactive oxygen species and prevent tissue damage produced by OFR.

Animals↗

PubMed1996

Naphthalene-induced oxidative stress in rats and the protective effects of vitamin E succinate.

Quinone metabolites of naphthalene (NAP) are known to produce lipid peroxidation. However, the ability of naphthalene to induce oxidative stress in experimental animals has not been extensively investigated. Furthermore, the effects of vitamin E succinate [(+)-alpha-tocopherol acid succinate; VES] on naphthalene-induced oxidative stress and tissue damage were assessed. Female Sprague-Dawley rats were treated with a single oral dose of 1100 mg naphthalene/kg (0.50 LD50) in corn oil. Vitamin E succinate-treated rats received 100 mg VES/kg/day orally for 3 d before naphthalene treatment, and 40 mg VES/kg/d after NAP administration. Hepatic and brain tissues and urine samples were collected 0, 12, 24, 48, and 72 h after NAP treatment. Naphthalene treatment resulted in a 2.1-fold increase in lipid peroxidation in liver and brain mitochondria at the 24-h time point. Increases in hepatic and brain mitochondrial lipid peroxidation in VES plus NAP-treated rats were 39-46% less than NAP treated rats at 24 h. DNA-single strand breaks increased 3.0-fold in hepatic tissues in NAP treated rats, and increased only 1.6-fold in VES protected rats at the 24-h time point. Glutathione (GSH) decreased by 83 and 49% in hepatic and brain tissues, respectively, in NAP-treated rats at the 24-h time point, while GSH content in VES plus NAP-treated rats decreased 47 and 21% in hepatic and brain tissues, respectively, at this same time point. Microsomal membrane fluidity, a measurement of membrane damage, increased 1.9- and 1.7-fold in liver and brain tissues, respectively, in NAP-treated rats, and only 1.3- and 1.2-fold in NAP plus VES-treated rats at the 24-h time point. The urinary excretion of malondialdehyde (MDA), formaldehyde (FA), acetaldehyde (ACT), and acetone (ACON) was determined at 0-96 h after NAP administration. Between 12-24 h after NAP administration maximal excretion of the four urinary lipid metabolites was observed, with increases of 4.5-, 2.7-, 2.3-, and 2.8-fold for MDA, FA, ACT, and ACON, respectively, at the 24-h time point. VES reduced the NAP-induced excretion of these urinary metabolites by 28-49% 24 h after NAP administration. These results support the hypothesis that NAP induces oxidative stress and tissue damage, and that vitamin E succinate provides significant protection.

Animals↗