PubMed · 4106672
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M L Salkie. 1971-10-23. Too many tests?. https://doi.org/10.1016/s0140-6736(71)92518-9
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Gut regulatory peptides bombesin (BBS) and neurotensin (NT) exert a wide spectrum of biological actions on gastrointestinal tissues and we have previously shown that they improve intestinal barrier function and oxidative stress in experimentally jaundiced rats. In the present study, we explored their potential action on liver histology and oxidative status in bile duct ligated rats. Seventy male Wistar rats were randomly divided into five groups: controls, sham operated, bile duct ligated (BDL), BDL + BBS (10 microg/kg, s.c. x3), BDL + NT (300 microg/kg, i.p.). At the end of the experiment, on day 10, serum total bilirubin and alanine aminotransferase (ALT) levels were determined and endotoxin was measured in portal and aortic blood. Liver tissue samples were examined histologically for evaluation of the ratio of portal tracts presenting changes of obstructive cholangiopathy and neutrophils' number in portal tracts. In addition, hepatic oxidative status was estimated on liver homogenates by measurements of lipid peroxidation (malondialdehyde), protein oxidation (protein carbonyl groups) and thiol redox state [reduced glutathione (GSH), oxidized glutathione (GSSG), total non-protein mixed disulfides (NPSSR) and protein thiols (PSH)]. Administration of BBS or NT significantly reduced portal and aortic endotoxaemia observed in obstructive jaundice. Both agents significantly ameliorated liver injury, as demonstrated by improvement of obstructive cholangiopathy and reduction of ALT. This effect was accompanied by prevention of lipid peroxidation, protein oxidation and decrease of the oxidized forms GSSG and NPSSR. Moreover, neutrophil accumulation in portal tracts was significantly decreased. In conclusion, this study shows that gut regulatory peptides BBS and NT reduce cholestatic liver injury, exerting protective effects on portal tract architecture, neutrophil infiltration and hepatic oxidative stress in bile duct ligated rats.
BACKGROUND: Insulin sensitizing agents may be useful in treatment of non-alcoholic fatty liver disease. AIM: A pilot study to evaluate the efficacy and safety of metformin in non-alcoholic fatty liver disease. METHODS: In an open labelled study, patients with histologically confirmed non-alcoholic fatty liver disease were given metformin (20 mg/kg) for 1 year. Insulin resistance (by log homeostasis assessment model analysis for insulin resistance and Quantitative Insulin Sensitivity Check Index) and post-treatment hepatic histology were compared with pre-treatment histology. RESULTS: Fifteen patients completed 1 year of treatment. During the initial 3 months, there was improvement in alanine aminotransferase and aspartate aminotransferase (P-value 0.01 and 0.02, respectively) along with improvement in insulin sensitivity. However, after 3 months, there was no further improvement in insulin sensitivity and there was gradual rise in aspartate aminotransferase and alanine aminotransferase back to pre-treatment levels. Among the 10 patients with post-treatment biopsy, three (33%), showed improvement in steatosis, two (20%) showed improvement in inflammation score and one (10%) showed improvement in fibrosis. CONCLUSION: Metformin treatment was associated with only a transient improvement in liver chemistries. A progressive, sustainable reduction in insulin sensitivity was not noted during treatment.