Disruption of the alveolar−endothelial barrier caused by inflammation leads to the progression of septic acute lung injury (ALI). In the present study, we investigated the beneficial effects of simvastatin on the endotoxin lipopolysaccharide (LPS)-induced ALI and its related mechanisms. A model of ALI was induced within experimental sepsis developed by intraperitoneal injection of a single non-lethal LPS dose after short-term simvastatin pretreatment (10−40 mg/kg orally). The severity of the lung tissue inflammatory injury was expressed as pulmonary damage scores (PDS). Alveolar epithelial cell apoptosis was confirmed by TUNEL assay (DNA fragmentation) and expressed as an apoptotic index (AI), and immunohistochemically for cleaved caspase-3, cytochrome C, and anti-apoptotic Bcl-xL, an inhibitor of apoptosis, survivin, and transcriptional factor, NF-kB/p65. Severe inflammatory injury of pulmonary parenchyma (PDS 3.33 ± 0.48) was developed after the LPS challenge, whereas simvastatin significantly and dose-dependently protected lung histology after LPS (p < 0.01). Simvastatin in a dose of 40 mg/kg showed the most significant effects in amelioration alveolar epithelial cells apoptosis, demonstrating this as a marked decrease of AI (p < 0.01 vs. LPS), cytochrome C, and cleaved caspase-3 expression. Furthermore, simvastatin significantly enhanced the expression of Bcl-xL and survivin. Finally, the expression of survivin and its regulator NF-kB/p65 in the alveolar epithelium was in strong positive correlation across the groups. Simvastatin could play a protective role against LPS-induced ALI and apoptosis of the alveolar−endothelial barrier. Taken together, these effects were seemingly mediated by inhibition of caspase 3 and cytochrome C, a finding that might be associated with the up-regulation of cell-survival survivin/NF-kB/p65 pathway and Bcl-xL.

• Klíčová slova
• NF-kB/p65, alveolar epithelial cells, apoptosis, simvastatin, survivin,
• MeSH
• akutní poškození plic * chemicky indukované   farmakoterapie   metabolismus   MeSH
• apoptóza MeSH
• cytochromy c metabolismus   MeSH
• endotoxiny škodlivé účinky   MeSH
• kaspasa 3 genetika   metabolismus   MeSH
• lidé MeSH
• lipopolysacharidy toxicita   MeSH
• NF-kappa B * metabolismus   MeSH
• plíce patologie   MeSH
• pneumocyty metabolismus   MeSH
• simvastatin škodlivé účinky   MeSH
• survivin genetika   MeSH
• upregulace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cytochromy c MeSH
• endotoxiny MeSH
• kaspasa 3 MeSH
• lipopolysacharidy MeSH
• NF-kappa B * MeSH
• simvastatin MeSH
• survivin MeSH

Hypertension is one of the most prevalent and powerful contributors of cardiovascular diseases. Malignant hypertension is a relatively rare but extremely severe form of hypertension accompanied with heart, brain, and renal impairment. Resveratrol, a recently described grape-derived, polyphenolic antioxidant molecule, has been proposed as an effective agent in the prevention of cardiovascular diseases. This study was designed to examine chronic resveratrol administration on blood pressure, oxidative stress, and inflammation, with special emphasis on cardiac structure and function in two models of experimental hypertension. The experiments were performed in spontaneously (SHRs) and malignantly hypertensive rats (MHRs). The chronic administration of resveratrol significantly decreased blood pressure in both spontaneously and malignant hypertensive animals. The resveratrol treatment ameliorated morphological changes in the heart tissue. The immunohistochemistry of the heart tissue after resveratrol treatment showed that both TGF-β and Bax were not present in the myocytes of SHRs and were present mainly in the myocytes of MHRs. Resveratrol suppressed lipid peroxidation and significantly improved oxidative status and release of NO. These results suggest that resveratrol prevents hypertrophic and apoptotic consequences induced by high blood pressure with more pronounced effects in malignant hypertension.

• Klíčová slova
• heart, resveratrol, spontaneously and malignant hypertension,
• MeSH
• antiflogistika farmakologie   terapeutické užití   MeSH
• antioxidancia terapeutické užití   MeSH
• apoptóza * účinky léků   MeSH
• hemodynamika účinky léků   MeSH
• hypertenze maligní farmakoterapie   enzymologie   patologie   patofyziologie   MeSH
• kardiotonika farmakologie   terapeutické užití   MeSH
• krysa rodu Rattus MeSH
• látky reagující s kyselinou thiobarbiturovou metabolismus   MeSH
• myokard patologie   MeSH
• NG-nitroargininmethylester chemie   farmakologie   MeSH
• oxidace-redukce MeSH
• potkani inbrední SHR MeSH
• protein X asociovaný s bcl-2 metabolismus   MeSH
• resveratrol chemie   farmakologie   terapeutické užití   MeSH
• srdeční komory účinky léků   patologie   patofyziologie   MeSH
• tělesná hmotnost účinky léků   MeSH
• velikost orgánu účinky léků   MeSH
• zánět komplikace   farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antiflogistika MeSH
• antioxidancia MeSH
• kardiotonika MeSH
• látky reagující s kyselinou thiobarbiturovou MeSH
• NG-nitroargininmethylester MeSH
• protein X asociovaný s bcl-2 MeSH
• resveratrol MeSH

In this paper, the potential antidote efficacy of commercially available formulations of various feed additives such as Minazel-Plus®, Mycosorb®, and Mycofix® was considered by recording their incidence on general health, body weight, and food and water intake, as well as through histopathology and semiquantitative analysis of gastric alterations in Wistar rats treated with the T-2 toxin in a single-dose regimen of 1.67 mg/kg p.o. (1 LD50) for 4 weeks. As an organic adsorbent, Mycosorb® successfully antagonized acute lethal incidence of the T-2 toxin (protective index (PI) = 2.25; p < 0.05 vs. T-2 toxin), and had adverse effects on body weight gain as well as food and water intake during the research (p < 0.001). However, the protective efficacy of the other two food additives was significantly lower (p < 0.05). Treatment with Mycosorb® significantly reduced the severity of gastric damage, which was not the case when the other two adsorbents were used. Our results suggest that Mycosorb® is a much better adsorbent for preventing the adverse impact of the T-2 toxin as well as its toxic metabolites compared with Minazel-plus® or Mycofix-plus®, and it almost completely suppresses its acute toxic effects and cytotoxic potential on the gastric epithelial, glandular, and vascular endothelial cells.

• Klíčová slova
• T-2 toxin, adsorbents, antidote, rats,
• MeSH
• adsorpce MeSH
• antidota chemie   farmakologie   MeSH
• časové faktory MeSH
• cévní endotel účinky léků   patologie   MeSH
• jodofory farmakologie   MeSH
• LD50 MeSH
• molekulární struktura MeSH
• otrava farmakoterapie   patologie   MeSH
• potkani Wistar MeSH
• potravinářské přísady chemie   farmakologie   MeSH
• T-2 toxin otrava   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• žaludeční sliznice účinky léků   patologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• antidota MeSH
• jodofory MeSH
• Mycofix MeSH Prohlížeč
• potravinářské přísady MeSH
• T-2 toxin MeSH

Increasing evidence suggests that apoptosis of tubular cells and renal inflammation mainly determine the outcome of sepsis-associated acute kidney injury (AKI). The study aim was to investigate the molecular mechanism involved in the renoprotective effects of simvastatin in endotoxin (lipopolysaccharide, LSP)-induced AKI. A sepsis model was established by intraperitoneal injection of a single non-lethal LPS dose after short-term simvastatin pretreatment. The severity of the inflammatory injury was expressed as renal damage scores (RDS). Apoptosis of tubular cells was detected by Terminal deoxynucleotidyl transferase-mediated dUTP Nick End Labeling (TUNEL assay) (apoptotic DNA fragmentation, expressed as an apoptotic index, AI) and immunohistochemical staining for cleaved caspase-3, cytochrome C, and anti-apoptotic Bcl-xL and survivin. We found that endotoxin induced severe renal inflammatory injury (RDS = 3.58 ± 0.50), whereas simvastatin dose-dependently prevented structural changes induced by LPS. Furthermore, simvastatin 40 mg/kg most profoundly attenuated tubular apoptosis, determined as a decrease of cytochrome C, caspase-3 expression, and AIs (p < 0.01 vs. LPS). Conversely, simvastatin induced a significant increase of Bcl-XL and survivin, both in the strong inverse correlations with cleaved caspase-3 and cytochrome C. Our study indicates that simvastatin has cytoprotective effects against LPS-induced tubular apoptosis, seemingly mediated by upregulation of cell-survival molecules, such as Bcl-XL and survivin, and inhibition of the mitochondrial cytochrome C and downstream caspase-3 activation.

• Klíčová slova
• Bcl-XL, cytochrome C, endotoxin, simvastatin, survivin, tubular apoptosis,
• MeSH
• akutní poškození ledvin chemicky indukované   farmakoterapie   genetika   patologie   MeSH
• apoptóza účinky léků   MeSH
• cytochromy c genetika   MeSH
• endotoxiny toxicita   MeSH
• epitelové buňky účinky léků   patologie   MeSH
• krysa rodu Rattus MeSH
• ledvinové kanálky účinky léků   patologie   MeSH
• ledviny účinky léků   zranění   metabolismus   patologie   MeSH
• lidé MeSH
• lipopolysacharidy toxicita   MeSH
• protein bcl-X genetika   MeSH
• simvastatin farmakologie   MeSH
• viabilita buněk účinky léků   MeSH
• zánět chemicky indukované   farmakoterapie   genetika   patologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cytochromy c MeSH
• endotoxiny MeSH
• lipopolysacharidy MeSH
• protein bcl-X MeSH
• simvastatin MeSH

Certain AChE reactivators, asoxime, obidoxime, K027, K048, and K075, when taken in overdoses and sometimes even when introduced within therapeutic ranges, may injure the different organs. As a continuation of previously published data, in this study, Wistar rats have sacrificed 24 hrs and 7 days after single im application of 0.1LD50, 0.5LD50 and 1.0LD50 of each reactivator, and examinated tissue samples were obtained for pathohistological and semiquantitative analysis. A severity of tissue alteration, expressed as different tissue damage scores were evaluated. Morphological structure of examinated tissues treated with of 0.1LD50 of all reactivators was comparable with the control group of rats. Moderate injuries were seen in visceral tissues treated with 0.5LD50 of asoxime, obidoxime and K027. Acute damages were enlarged after treatment with 0.5LD50 and 1.0LD50 of all reactivators during the next 7 days. The most prominent changes were seen in rats treated with 1.0LD50 of K048 and K075 (P < 0.001 vs. control and asoxime-treated group). All reactivators given by a single, high, unitary dose regimen, have an adverse effect not only on the main visceral tissue, but on the whole rat as well, but the exact mechanism of cellular injury remains to be confirmed in further investigation.

• MeSH
• biopsie MeSH
• chemické bojové látky škodlivé účinky   chemie   toxicita   MeSH
• histocytochemie MeSH
• krysa rodu Rattus MeSH
• LD50 MeSH
• molekulární struktura MeSH
• orgánová specificita MeSH
• oximy aplikace a dávkování   škodlivé účinky   chemie   toxicita   MeSH
• plíce účinky léků   metabolismus   patologie   MeSH
• vnitřnosti účinky léků   patologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• žaludek účinky léků   patologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chemické bojové látky MeSH
• oximy MeSH