Lidocaïne test for easier and less time consuming assessment of liver function in several hepatic injury models.

PURPOSE: In this study, we developed an ex vivo functional assay to assess liver metabolic capacity adapted from the lidocaïne test in rats. METHODS: Animals used were subjected to different models of liver injury: hypothermic ischemia (H/I, n = 8), ischemia-reperfusion (I/R, n = 8) and CCl4 induced liver cirrhosis (n = 11), and compared with sham operated rats (n = 5). Livers were then extracted and a fragment of whole tissue was incubated with lidocaïne for 15, 30, 60, 120, 240, 360, and 720 min at which both lidocaïne and its major metabolite monoethylglycinexylidide (MEGX) were measured by high performance liquid chromatography (HPLC). A histological study and biochemical assays (transaminase levels) were also performed to further evaluate and confirm our data. RESULTS: Pharmacokinetic profile of lidocaïne metabolism in sham-operated animals revealed that the maximum concentration of MEGX is achieved at 120 min. Both lidocaïne metabolism and MEGX formation levels were significantly altered in all three models of hepatic injury. The extent of hepatic damage was confirmed by increased levels of transaminase levels and alteration of hepatocyte's structure with areas of necrosis. CONCLUSION: Our method provides reliable and reproducible results using only a small portion of liver which allows for a fast and easy assessment of liver metabolic capacity. Moreover, our method presents an alternative to the in vivo technique and seems more feasible in a clinical setting.

[Drug induced colitis: review article]. / Les colites médicamenteuses: revue de la littérature.

Frequency of colitis induced by drugs is often under estimated. Antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDS) are usually incriminated. In this study, we classified colitis according to the main responsible drug with a focus on clinical symptomatology, physiopathology, evolution, and complications. We describe colitis due to antibiotics, NSAIDS, laxatives, vasoconstrictive agents, oestroprogestatives, chemotherapy and drugs induced microscopic colitis. The last one represents a particular case; it can be idiopathic, infectious or drugs induced. Its physiopathology is not well known and its diagnosis is based only on histologic criterion. Drug responsibility is easy to determine only for pseudomembranous colitis. In the other cases, chronology is very variable and the clinical, endoscopic and histological elements are rarely specific. Because of the large number of drugs that may induce colitis, it is necessary to search for potentially responsible drugs, especially if there is no obvious cause of the colitis.

Protection of cellular and mitochondrial functions against liver ischemia by N-benzyl-N'-(2-hydroxy-3,4-dimethoxybenzyl)-piperazine (BHDP), a sigma1 ligand.

We investigated the antiischemic properties of a new compound N-benzyl-N'-(2-hydroxy-3,4-dimethoxybenzyl)-piperazine (BHDP), having high affinity and selectivity for the sigma(1) receptor, in two different models of ischemia. The first was an experimental model of rat liver normothermic ischemia-reperfusion. Rats were pretreated with different doses of BHDP (0.5, 2.5 or 10 mg/kg/day, or solvent alone) and subjected to 90 min normothermic ischemia followed by either 30 or 120 min reperfusion. The second model was a hypothermic model of ischemia in which livers were incubated for 24 h at 4 degrees C in a preservation solution in the absence or presence of increasing BHDP concentrations (0.5, 2.5 or 10 microg/ml). These different ischemic conditions induced huge alterations in hepatocyte functions (membrane leakage of alanine aminotransferase and aspartate aminotransferase, decreased metabolic capacities evaluated by the ability of the liver to transform lidocaine, alterations of mitochondrial functions characterized by a decrease in ATP synthesis and the appearance of histological damages). Pretreatment of rats with BHDP alleviated these deleterious ischemia-reperfusion effects in a dose-dependent manner at both the cellular and mitochondrial levels. The protection of mitochondrial functions was almost complete at a dosage of 10 mg/kg/day during normothermic ischemia and 10 microg/ml in the preservation liquid during hypothermic ischemia. In addition, BHDP significantly reduced the histological damage. These data demonstrate that BHDP protects liver against the deleterious effects of ischemia-reperfusion and suggest that sigma(1) receptors play an important role in the protective effect.