Liliana Torres-González

Temporal relationship of serum markers and tissue damage during acute intestinal ischemia/reperfusion.

OBJECTIVE: It is essential to identify a serological marker of injury in order to study the pathophysiology of intestinal ischemia reperfusion. In this work, we studied the evolution of several serological markers after intestinal ischemia reperfusion injury in rats. The markers of non-specific cell damage were aspartate aminotransferase, alanine aminotransaminase, and lactic dehydrogenase, the markers of inflammation were tumor necrosis factor alpha, interleukin-6, and interleukin-1 beta, and the markers of intestinal mucosal damage were intestinal fatty acid binding protein and D-lactate. We used Chiús classification to grade the histopathological damage. METHODS: We studied 35 Wistar rats divided into groups according to reperfusion time. The superior mesenteric artery was clamped for 30 minutes, and blood and biopsies were collected at 1, 3, 6, 12, 24, and 48 hours after reperfusion. We plotted the mean ± standard deviation and compared the baseline and maximum values for each marker using Students t-test. RESULTS: The maximum values of interleukin-1 beta and lactic dehydrogenase were present before the maximal histopathological damage. The maximum tumor necrosis factor alpha and D-lactate expressions coincided with histopathological damage. Alanine aminotransaminase and aspartate aminotransferase had a maximum expression level that increased following the histopathological damage. The maximum expressions of interluken-6 and intestinal fatty acid binding protein were not significantly different from the Sham treated group. CONCLUSION: For the evaluation of injury secondary to acute intestinal ischemia reperfusion with a 30 minute ischemia period, we recommend performing histopathological grading, quantification of D-lactate, which is synthesized by intestinal bacteria and is considered an indicator of mucosal injury, and quantification of tumor necrosis factor alpha as indicators of acute inflammation three hours after reperfusion.

Hepatic Ischemia/Reperfusion Injury Is Diminished by Atorvastatin in Wistar Rats

BACKGROUND AND AIMS Temporal occlusion of the hepatoduodenal ligament (HDL) is often used during liver surgeries in order to reduce blood loss, resulting in ischemia/reperfusion injury (I/R). The aim of the study was to investigate the effects of atorvastatin (ATOR) on hepatic I/R injury and on serum levels of tumor necrosis factor-alpha (TNF-α), endothelin-1 (ET-1), antithrombin III (ATIII) and intracellular adhesion molecule-1 (ICAM-1). METHODS Liver ischemia was induced in Wistar rats by clamping the HDL for 60 min, followed by either 60 or 180 min reperfusion. Rats received either vehicle or 10 mg/kg ATOR before hepatic I/R. Control group received sham surgery. Livers were examined for histological damage and serum AST, ALT, TNF-α, ET-1, ATIII and ICAM-1 concentrations were measured. RESULTS After I/R, AST and ALT were significantly elevated, ATIII levels were significantly depleted, both TNF-α and ICAM-1 levels increased and ET-1 was significantly elevated (at 180 min). ATOR pretreatment attenuated these alterations and diminished histological injury scores. CONCLUSIONS Our results show that ATOR protects the liver from I/R injury.

Hepatoprotective effect of commercial herbal extracts on carbon tetrachloride-induced liver damage in Wistar rats

Background: Various hepatoprotective herbal products from plants are available in Mexico, where up to 85% of patients with liver disease use some form of complementary and alternative medicine. However, only few studies have reported on the biological evaluation of these products. Objective: Using a model of carbon tetrachloride (CCl4)-induced hepatotoxicity in rats, we evaluated the effects of commercial herbal extracts used most commonly in the metropolitan area of Monterrey, Mexico. Materials and Methods: The commercial products were identified through surveys in public areas. The effect of these products given with or without CCl4 in rats was evaluated by measuring the serum concentrations of aspartate amino transferase (AST) and alanine amino transferase (ALT), and histopathological analysis. Legalon® was used as the standard drug. Results: The most commonly used herbal products were Hepatisan® capsules, Boldo capsules, Hepavida® capsules, Boldo infusion, and milk thistle herbal supplement (80% silymarin). None of the products tested was hepatotoxic according to transaminase and histological analyses. AST and ALT activities were significantly lower in the Hepavida+CCl4-treated group as compared with the CCl4-only group. AST and ALT activities in the silymarin, Hepatisan, and Boldo tea groups were similar to those in the CCl4 group. The CCl4 group displayed submassive confluent necrosis and mixed inflammatory infiltration. Both the Hepatisan+CCl4 and Boldo tea+CCl4 groups exhibited ballooning degeneration, inflammatory infiltration, and lytic necrosis. The silymarin+CCl4 group exhibited microvesicular steatosis. The Hepavida+CCl4- and Legalon+CCL4-treated groups had lower percentages of necrotic cells as compared with the CCl4-treated group; this treatment was hepatoprotective against necrosis. Conclusion: Only Hepavida had a hepatoprotective effect.

Is Ischemic Preconditioning a Useful Therapeutic Strategy in Liver Transplantation? Results from the First Pilot Study in Mexico.

BACKGROUND AND AIMS The protective effect of ischemic preconditioning (IP) in liver transplantation (LT) has been studied with controversial results. We undertook this study to investigate whether IP of cadaveric donor livers is protective to allografts. METHODS IP (LT + IP, n = 6) was induced by 10-min hilar clamping. These were compared to cadaver donors with no IP (LT, n = 7). Clinical data and blood were obtained in donors and recipients for biochemical and inflammatory mediator (IM) measurements (P-selectin, leukotriene B4, myeloperoxidase, ICAM-1, IL-1, IL-6, and TNF-α). Liver tissue samples were obtained from donors and recipients (90 min after reperfusion). RESULTS No significant differences were found in demographic characteristics between donors and recipients. When comparing both groups (LT + IP vs. LT only), ICU stay was longer in LT + IP group. For biochemical parameters, a significant difference was found only with a higher total bilirubin at postoperative day 3 in LT + IP group. There was no statistical difference in IM between LT and LT + IP groups at different stages of the study. Histological analysis of donor grafts indicated the presence of steatosis (50%) in one graft from the LT + IP group. However, in post-reperfusion biopsies neither neutrophil infiltration nor grade of necrosis showed significant difference between groups. No incidence of primary graft nonfunction (PGNF) was observed and graft and patient survival was similar in the two groups at 24 months. CONCLUSION IP does not seem to protect against I/R injury in cadaveric LT, and no PGNF was seen.

Autoimmune hepatitis in Mexican patients.

To the Editor: We read with interest the paper by Wong and colleagues in which ethnic differences were observed in patients with autoimmune hepatitis (AIH); Hispanics had the highest prevalence of cirrhosis (55%), and Asians had poorer survival outcomes. They included 20 patients, 19 of whom were alive after a follow-up of 71.7 months. Race/ ethnicity-specific disparities in AIH epidemiology may reflect underlying genetic differences, contributing to variations in disease severity, response to therapy, and overall mortality.1 We recently published our experience in AIH in a group of Mexican patients, and were able to confirm in a larger sample of 73 patients, that cirrhosis was common (56%) on admission2; despite this fact, survival in AIH was 22.2 years (95% confidence interval, 18-26 y), confirming Wong and colleague’s findings. Besides, we applied in this group of patients both the revised classification of AIH (R-IAIHG)3 and the Simplified criteria (SC).4 The R-IAIHG exhibited a sensitivity of 95%, specificity of 90%, and positive predictive value and negative predictive value of 93% for both. In contrast, the SC had a lower sensitivity (65%) but a higher specificity (100%), positive predictive value of 100%, and negative predictive value of 68%. Patients with AIH who were classified as nondiagnostic by the SC system did respond to immunosuppressive treatment, confirming the diagnoses of AIH. These patients exhibited lower levels of immunoglobulin G, titers of non-organ–specific autoantibodies, and less features of typical AIH in the liver biopsy. The frequency of cirrhosis at the initial evaluation in our study is intermediate between that of black North American patients (85%) and white North American patients (38%).5 Mexican mestizos have a high level of genetic biological diversity, mainly with racial admixture of EuroAmerican, Afro-American, and IndoAmerican genes and differ greatly among geographical regions and ethnic groups.6 This may help to explain the differences in the outcome and different clinical manifestations of AIH.

Re-treatment with Highly Purified nIFNα in Mexican Nonresponder Patients with Chronic Genotype 1 Hepatitis C

BACKGROUND AND AIMS We undertook this study to evaluate the virological response to and presence of adverse events to natural interferon α (nIFNα; Multiferon®) treatment in previously nonresponsive Mexican patients chronically infected with genotype 1 hepatitis C. METHODS Thirty-nine patients received a 4-week induction of 5 days/week of 6 MU nIFNα plus weight-based ribavirin followed by 3 MU of nIFNα three times a week for 44 weeks. The relationship between viral response and incidence of adverse events was analyzed. RESULTS Early viral response (EVR) was age- and sex-dependent, with older male patients being less responsive. Sustained viral response (SVR) was evaluated according to: a) intention to treat analysis, b) 48-week treatment and 24-week follow-up (16 patients), and c) patients with EVR (11 patients). None of the factors was significantly different in groups a) and b); however, in group c) there was a better response with a marked viral load decline in younger patients and in patients aged 50 years and older. Five of 39 (13%) patients who completed treatment presented with an SVR. The most common adverse effect was asthenia in 27% of patients. CONCLUSIONS nIFNα could be a useful strategy for re-treatment in chronic hepatitis C, genotype 1, in previously nonresponsive patients. Confirmation of these data in a larger population is required.

Nephroprotective Effect of Sonchus oleraceus Extract against Kidney Injury Induced by Ischemia-Reperfusion in Wistar Rats

Introduction Kidney ischemia-reperfusion (I/R) injury is the main cause of delayed graft function in solid organ transplantation. Sonchus oleraceus is a plant with well-known antioxidant and anti-inflammatory activities; however, its effects on renal I/R are unknown. Objective To evaluate whether S. oleraceus extract (S.O.e.) has nephroprotective activity in an I/R model in Wistar rats. Materials and Methods Animal groups (n = 6): sham, I/R (45 min/15 h), S.O.e (300 mg/kg p.o.), and S.O.e + I/R (300 mg/kg, p.o.; 45 min/15 h). Renal function, proinflammatory cytokines, alanine aminotransferase, markers of oxidative stress, and histology were evaluated. Results None of the mediators evaluated differed significantly between the S.O.e and sham groups. Levels of blood urea nitrogen (BUN), creatinine, malondialdehyde (MDA), and proinflammatory cytokines were higher, and superoxide dismutase (SOD) was lower in the I/R group than in the sham group. Histology showed tubular epithelial necrosis in the medulla and cortex in the I/R group. In the S.O.e + I/R group, S.O.e pretreatment attenuated the I/R-induced increases in BUN, creatinine, MDA, and proinflammatory cytokines induced, SOD was maintained, and histology showed discontinuous necrosis in the medulla but no necrosis in the cortex. Conclusions S.O.e was neither hepatotoxic nor nephrotoxic. S.O.e. pretreatment showed a nephroprotective effect against I/R.

Comparative Effects of Triflusal, S-Adenosylmethionine, and Dextromethorphan over Intestinal Ischemia/Reperfusion Injury

Ischemia/reperfusion (I/R) is a condition that stimulates an intense inflammatory response. No ideal treatment exists. Triflusal is an antiplatelet salicylate derivative with anti-inflammatory effects. S-adenosylmethionine is a metabolic precursor for glutathione, an endogenous antioxidant. Dextromethorphan is a low-affinity N-methyl-D-aspartate receptor inhibitor. There is evidence that these agents modulate some of the pathways involved in I/R physiopathology. Intestinal I/R was induced in rats by clamping the superior mesenteric artery for 60 minutes, followed by 60 minutes of reperfusion. Rats either received saline or the drugs studied. At the end of the procedure, serum concentrations of tumor necrosis factor-alpha (TNF-alpha), malonaldehyde (MDA), and total antioxidant capacity (TAC) were determined and intestinal morphology analyzed. I/R resulted in tissue damage, serum TNF-alpha and MDA elevations, and depletion of TAC. All drugs showed tissue protection. Only triflusal reduced TNF-alpha levels. All drugs lowered MDA levels, but only triflusal and S-adenosylmethionine maintained the serum TAC.