R. Goutier

Human myeloperoxidase activity is inhibited in vitro by quercetin. Comparison with three related compounds

Quercetin is an effective inhibitor of human myeloperoxidase (MPO) activity, both with purified enzyme (IC50=3.5 μM) and in a system using stimulated human neutrophils. Quercetin is significantly more potent than three other related compounds (rutin, rutin sulfate and troxerutin) and than methimazole, a previously-known myeloperoxidase inhibitor. The inhibitory activity of quercetin is of the competitive type. Moreover, quercetin is directly able to scavenge hypochlorous acid (HOCl), a chlorinated species generated by the, MPO/H2O2/Cl− system.

Thromboxane and prostacyclin release in adult respiratory distress syndrome

Plasma thromboxane B2 (TXB2) and 6-ketoprostaglandin F1α (6-keto-PGF1α) were measured in 84 patients at risk of developing adult respiratory distress syndrome (ARDS) (44 patients following multiple trauma, 29 patients following abdominal surgery and 11 patients with acute pancreatitis). Forty-nine of these 84 patients developed an ARDS. High (>140 pg/ml plasma) TXB2 values were found in 52/84 patients. The median values of TXB2 were: 360 pg/ml in multiple injured, 250 pg/ml in abdominal surgery and 410 pg/ml in acute pancreatitis patients. The median TXB2 value was 575 pg/ml in patients developing ARDS and 140 pg/ml in those without this complication: this difference was statistically significant (p<0.05). The median values of 6-keto-PGF1α were 55pg/ml in multiple injured, 25 pg/ml in abdominal surgery and 120 pg/ml in acute pancreatitis patients. The median 6-keto-PGF1α value was 122 pg/ml in ARDS patients and 25 pg/ml in non-ARDS patients (statistically significant: p<0.05). High TXB2 and 6-keto-PGF1α values were particularly related to sepsis in abdominal surgery patients (p<0.05) and in multiple injured patients (p<0.01). No relation could be established between abnormal TXB2 or 6-keto-PGF1α values and death. High TXB2 values often persisted for several days and were observed particularly at the time ARDS diagnostic criteria were fulfilled. An imbalance between TXB2 and 6-keto-PGF1α was observed: 6-keto-PGF1α values were always lower than TXB2 values and did not persist for more than 24 h except in four cases. Our data demonstrate a significant production of prostanoids in ARDS patients particularly in sepsis and indicate a disturbance in balance of the prostacyclin/thromboxane axis.

Complementary procedures for pro- and anti-lipoperoxidant activity measurements

Evaluation of lipoperoxidation is performed by 2 methods, the first one measuring the amount of peroxyfunction (−OOH) at a given time, and the second one measuring the accumulation of a degradation product against time. The combination of the 2 methods allows us to investigate the kinetics of lipoperoxidation and to demonstrate, for example, the accelerating effect of lidocaine on autoxidation processes.

Stimulation of cyclooxygenase by activated human neutrophils is enhanced by uric acid

Activated human neutrophils supernatant enhances prostanoids production by bull seminal cyclooxygenase (455% of control). Superoxide anion and hydrogen peroxide are not involved in this stimulation, in these experimental conditions. Myeloperoxidase (by its hemic nature) and HPETEs (by their -OOH function) could trigger cyclooxygenase. In the presence of uric acid (10(-3) M), a potent hydroxyl radical scavenger, the cyclooxygenase stimulation by supernatant is increased until 709% of the control.

Oxygen, Free Radicals, Shock and Trauma

In atoms and molecules, the electrons generate, by rotation, a magnetic field represented by a vector, the spin. Generally, all the electrons are paired, opposing their spins, the resulting magnetic field being null. In molecules, electrons of neighbouring atoms are paired, forming covalent bonds, which can be broken by a sufficient amount of energy; after this rupture, two electrons become unpaired and the implicated atoms or molecules acquire a magnetic field (Fig. 1). The energy can be furnished by radiations (UV, ionizing radiations) and by chemical or enzymatic reactions. Such atoms or molecules presenting an odd number of electrons, and thus a magnetic field, are called free radicals.

Trypsin-like activity and thromboxane release in adult respiratory distress syndrome.

Plasmatic immunoreactive trypsin (IRT), thromboxane and trypsin-like enzymatic activity were measured in 117 patients at risk of developing adult respiratory distress syndrome (ARDS) (53 multiple injury, 30 abdominal surgery, 17 acute pancreatitis, 12 burnt and 5 disseminated intravascular coagulation patients). 69 of these patients developed ARDS. Immunoreactive trypsin and thromboxane were measured by radio-immuno-assay and trypsin-like enzymatic activity by spectrophotometry, using a specific chromogenic substrate. Mean IRT value was 675 ng/ml in ARDS and 265 ng/ml in non ARDS patients (p less than 0.05). Mean IRT value was 685 ng/ml in septic and 170 ng/ml in non septic patients (p less than 0.01). An abnormal trypsin-like enzymatic activity was measured in 26 ARDS patients. In 60 patients (37 ARDS and 23 non ARDS), thromboxane appeared in plasma simultaneously or about 24 hours after the beginning of IRT release. The importance of thromboxane release parallels the intensity of IRT. Originating from pancreas, trypsin can appear in plasma either by absorption from gastrointestinal tract or after pancreatic ischemia.

Trypsin-like Activity in Burn and Sepsis

A variety of insults (such as trauma, burns, acute pancreatitis and so on…) are accompanied by shock and often lead to the development of Adult Respiratory Distress Syndrome (ARDS) which defines a clinical and physiological sydrome characterized by an increase in pulmonary permeability with interstitial edema, subsequent hypoxemia and severe respiratory failure and by a high rate of mortality (50 to 70% of patients) (1,2).