Combined saline and vildagliptin induced M2 macrophage polarization in hepatic injury induced by acute kidney injury.

Acute kidney injury (AKI) is a prevalent medical condition accompanied by mutual affection of other organs, including the liver resulting in complicated multiorgan malfunction. Macrophages play a vital role during tissue injury and healing; they are categorized into "classically activated macrophages" (M1) and "alternatively activated macrophages" (M2). The present study investigated and compared the conventional fluid therapy vs Dipeptidyl peptidase 4 inhibitor (DPP-4i) vildagliptin on the liver injury induced by AKI and evaluated the possible molecular mechanisms. Thirty rats comprised five groups (n = 6 rats/group): control, AKI, AKI+saline (received 1.5 mL of normal saline subcutaneous injection), AKI+vildagliptin (treated with oral vildagliptin 10 mg/kg), AKI+saline+vildagliptin. AKI was induced by intramuscular (i.m) injection of 50% glycerol (5 ml/kg). At the end of the work, we collected serum and liver samples for measurements of serum creatinine, blood urea nitrogen (BUN), alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrotic factor-α (TNF-α), and interleukin-10 (IL-10). Liver samples were processed for assessment of inducible nitric oxide synthase (iNOS) as a marker for M1, arginase 1 (Arg-1) as an M2 marker, c-fos, c-Jun, mitogen-activated protein kinase (MAPK), activator protein 1 (AP-1), and high-mobility-group-box1 (HMGB1) protein. The difference was insignificant regarding the relative expression of AP-1, c-Jun, c-fos, MAPK, and HMGB between the AKI+saline group and the AKI+Vildagliptin group. The difference between the same two groups concerning the hepatic content of the M1 marker (iNOS) and the M2 marker Arg-1 was insignificant. However, combined therapy produced more pronounced changes in these markers, as the difference in their relative expression between the AKI+saline+Vildagliptin group and both the AKI+saline group and the AKI+Vildagliptin group was significant. Accordingly, we suggest that the combined saline and vildagliptin hepatoprotective effect involves the downregulation of the MAPK/AP-1 signaling pathway.

Serum miR-122 and miR-192 as biomarkers of intrinsic and idiosyncratic acute hepatotoxicity: A quantitative real-time polymerase chain reaction study in adult albino rats.

miR-122 and miR-192 were investigated as indicators of toxic liver injury caused by acetaminophen, but their role in idiosyncratic toxic liver injury remains controversial. So, this work aimed to assess and compare the expressions of miR-122 and miR-192 in two different types of toxic liver injury (intrinsic [acetaminophen] and idiosyncratic [diclofenac]). Forty male adult Wistar albino rats were divided into equal five groups, in which serum liver enzymes; microRNAs (miRNAs) expressions (miR-122 and miR-192) and histopathological findings were studied. The present study showed that (1) miR-122 and miR-192 are good serum biomarkers of toxic liver injury whatever its etiology, as their serum levels exhibited a significantly earlier increase and earlier return to normal baseline levels as compared to serum aminotransferase levels; (2) miR-122 is more specific than miR-192; and (3) both serum levels of miR-122 and miR-192 showed non-significant differences in relation to the type of toxic liver injury.

Exendin-4, a glucagon-like peptide-1 receptor agonist downregulates hepatic receptor for advanced glycation end products in non-alcoholic steatohepatitis rat model.

CONTEXT: Exendin-4, a glucagon-like peptide-1 receptor agonist has been shown to have curative effects on hepatic steatosis in murine models. OBJECTIVE: The present study aimed to elucidate the effect of Exendin-4 on hepatic receptor for advanced glycation end products (RAGE) mRNA expression in non-alcoholic steatohepatitis (NASH) rat model induced by high-fat diet. METHODS: NASH was induced by high-fat diet intake, and Exendin-4 was given in two different doses. After 12 weeks, liver enzyme levels, hepatic triglycerides, antioxidant enzymes and malondialdehyde (MDA) levels, and mRNA RAGE was detected using RT-PCR. RESULTS: Exendin-4 in high dose reduced significantly liver enzymes activity, hepatic triglycerides, MDA levels and hepatic mRNA RAGE expression levels with significantly higher antioxidant enzymes activity. CONCLUSIONS: Our results give further insights into the mechanisms underlying the curative role of Exendin-4 in NASH, suggesting that interference with RAGE may be a useful therapeutic approach to NASH.