stilbenes and Multiple-Organ-Failure

Therapeutic effects of continuous intravenous infusions of solvent-free low doses of resveratrol on organ injury and systemic consequences resulting from severe hemorrhagic shock in rats were studied. Hemorrhagic shock was induced by withdrawing arterial blood until a mean arterial blood pressure (MAP) of 25-30 mmHg was reached. Following a shock phase of 60 min, rats were resuscitated with the withdrawn blood plus lactated Ringer's. Resveratrol (20 or 60 μg/kg × h) was continuously infused intravenously starting with the resuscitation phase (30 min) and continued until the end of the experiment (total treatment time 180 min). Animals of the shock control group received 0.9% NaCl solution. After the observation phase (150 min), rats were sacrificed. Resveratrol significantly stabilized the MAP and peripheral oxygen saturation after hemorrhagic shock, decreased the macroscopic injury of the small intestine, significantly attenuated the shock-induced increase in tissue myeloperoxidase activity in the small intestine, liver, kidney and lung, and diminished tissue hemorrhages (particularly in the small intestine and liver) as well as the rate of hemolysis. Already very low doses of resveratrol, continuously infused during resuscitation after severe hemorrhagic shock, can significantly improve impaired systemic parameters and attenuate multiple organ damage in rats.

Topics: Animals; Blood Glucose; Blood Pressure; Disease Models, Animal; Dose-Response Relationship, Drug; Hematocrit; Hemoglobins; Intestine, Small; Isotonic Solutions; Kidney; Lactic Acid; Liver; Lung; Male; Multiple Organ Failure; Peroxidase; Rats; Rats, Wistar; Resuscitation; Resveratrol; Ringer's Lactate; Shock, Hemorrhagic; Sodium Chloride; Stilbenes

Polydatin (PD), a monocrystalline and polyphenolic drug isolated from a traditional Chinese herb (Polygonum cuspidatum), is protective against mitochondrial dysfunction and has been approved for clinical trials in the treatment of shock. However, whether the administration of PD has a therapeutic effect on multiple-organ dysfunction syndrome (MODS) requires investigation.. MODS was induced in Sprague-Dawley rats via hemorrhage and ligation and puncture of cecum-induced sepsis. The rats were divided into three groups as follows: MODS + PD, MODS + normal saline, and a control group (no treatment). Survival time, blood biochemical indexes, and histopathologic changes in various organs were evaluated; serum oxidative stress (advanced oxidative protein products [AOPPs]) and proinflammatory cytokines (tumor necrosis factor-α, interleukin 1β, and interleukin 6) were assayed using enzyme-linked immunosorbent assay. Apoptosis-related protein expression (B-cell lymphoma-2 [Bcl-2] and Bax) was assayed by immunohistochemical and Western blotting methods, whereas caspase-3 activity was assayed by spectrophotometry.. PD improved organ function, prolonged survival time, and reduced MODS incidence and serum levels of AOPPs and proinflammatory cytokines. It also decreased Bax levels and caspase-3 activity and increased Bcl-2 levels in the kidney and liver.. PD may serve as a potential therapeutic for MODS, as it suppresses oxidative stress, inhibits inflammatory response, attenuates apoptosis, and protects against mitochondrial dysfunction.

Topics: Animals; Caspase 3; Cytokines; Female; Glucosides; Multiple Organ Failure; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; Stilbenes

This paper presents a primary study of the treatment of experimental multiple system organ failure (MSOF) in rats. The rats were pretreated with xanthine oxidase inhibitor allopurinol, the energy metabolism regulator fructose-1,6-diphosphate (FDP) and purified Chinese herbal medicine polydatin. The incidence of MSOF decreased from 71.4% in the untreated group to 35.7%, 47.1% and 16.7% in treated groups, respectively, while the mean survival time was prolonged to 38.5h, 30.2h and 41.7h in treated groups, respectively, as compared with 26.4h in the untreated group. In addition to the known antioxidant effect of the allopurinol, this study also suggests that FDP and polydatin enhance the capacity of antioxidtion.

Topics: Allopurinol; Animals; Antioxidants; Free Radicals; Fructose-Bisphosphatase; Glucosides; Glutathione Peroxidase; Male; Malondialdehyde; Multiple Organ Failure; Oxygen; Rats; Rats, Inbred Strains; Stilbenes; Superoxide Dismutase