Effect of trichloroethylene (TCE) toxicity on the enzymes of carbohydrate metabolism,brush border membrane and oxidative stress in kidney and other rat tissues

Trichloroethylene (TCE), an industrial solvent, is a major environmental contaminant. Histopathological examinations revealed that TCE caused liver and kidney toxicity and carcinogenicity. However, biochemical mechanism and tissue response to toxic insult are not completely elucidated. We hypothesized that TCE induces oxidative stress to various rat tissues and alters their metabolic functions. Male Wistar rats were given TCE (1000 mg/kg/day) in corn oil orally for 25 d. Blood and tissues were collected and analyzed for various biochemical and enzymatic parameters. TCE administration increased blood urea nitrogen, serum creatinine, cholesterol and alkaline phosphatase but decreased serum glucose, inorganic phosphate and phospholipids indicating kidney and liver toxicity. Activity of hexokinase, lactate dehydrogenase increased in the intestine and liver whereas decreased in renal tissues. Malate dehydrogenase and glucose-6-phosphatase and fructose-1, 6-bisphosphatase decreased in all tissues whereas increased in medulla. Glucose-6-phosphate dehydrogenase increased but NADP-malic enzyme decreased in all tissues except in medulla. The activity of BBM enzymes decreased but renal Na/Pi transport increased. Superoxide dismutase and catalase activities variably declined whereas lipid peroxidation significantly enhanced in all tissues. The present results indicate that TCE caused severe damage to kidney, intestine, liver and brain; altered carbohydrate metabolism and suppressed antioxidant defense system.     

Induction antibody therapy in renal transplantation using early steroid withdrawal: long-term results comparing anti-IL2 receptor and anti-thymocyte globulin

Background

The present study intends to investigate the effects of anti-IL2 receptors (anti-IL2R) vs. lymphocyte-depleting agents in the early steroid withdrawal (ESW) scheme.

Methods

This is a retrospective cohort of 167 consecutive adult renal transplant recipients. Immunosuppression was based on tacrolimus and mycophenolate mofetil. Antibody induction therapy was carried out with lymphocyte-depleting agent (thymoglobulin) or anti-IL2R (Basiliximab or Daclizumab). ESW protocol was performed by administering intravenous methlyprednisolone as follows: 500 mg on day 0, 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, and then stopped.

Results

Among the 167 studied patients, 79 (47.3%) received anti-IL2R and 88 (52.7%) received thymoglobulin induction. Significantly fewer episodes of acute rejection were seen at one year in patients treated with thymoglobulin as compared to anti-IL2R (25.6% vs. 11.4%, p = 0.01). At five years, a significant difference in graft survival was observed in anti-IL2R-treated patients compared with thymoglobulin (83.5% vs. 95.5%, p = 0.01). Multivariate analysis disclosed that female sex, antibody induction therapy using thymoglobulin and a trough tacrolimus level higher than 10 were protective factors against acute rejection, while there was a trend to increased risk of acute rejection at first year post-transplantation in patients presenting delayed graft function (DGF). Antibody induction was independently associated with patient and graft survival at five years (OR 0.213, 95% CI 0.046–0.991, p = 0.04).

Conclusion

ESW scheme seems to be safe and its use is beneficial since there are fewer adverse effects. Thymoglobulin induction therapy is associated with fewer rejection episodes. Induction therapy with thymoglobulin is associated with higher patient and allograft survival when comparing with anti-IL2R.