MATERIALS AND METHODS: Wistar male rats (3 months old, 160- 230 grams) were divided into 4 groups that consisted of six rats in each group. The obesity model was induced through the administration of high-fat diet for a month (OB1), two months (OB2), and four months (OB4). Standard chow was provided for the control group for four months. After the specified date the rats were euthanized and the liver and retroperitoneal white adipose tissue (RWAT) were harvested. We performed RT-PCR to assess the mRNA expressions involved in proinflammatory mediators, fibrosis and antifibrosis signaling. Sirius red staining was performed to assess liver fibrosis. Data were analyzed with SPSS 23 for Windows with significance set as p<0.05.

RESULTS: Obesity-induced high-fat diet stimulated an increase of body mass index (BMI) in the OB groups (p<0.05) compared to the control group. Increased BMI was followed by upregulation of proinflammatory mediators (MCP-1, CD68, TLR4, and NFκB) of the RWAT and liver in the obese groups (p<0.05), which promoted hepatic fibrosis in triad portal areas and upregulation of TGFβ (p<0.05) mRNA expression as well as downregulation of HGF and c-Met (p<0.05). In addition, hepatic ppET1 and EDNRB mRNA level expressions (p<0.05) were obviously upregulated in the obese groups followed by downregulation of eNOS (p<0.05) mRNA expressions.

MATERIALS AND METHODS: Diabetic condition was performed with intraperitoneal injection of Streptozotocin 60 mg/kg body weight (BW) in Sprague Dawley rats (2 months old, n=24), and were kept for 1, 2, and 4 months (DM1, DM2, and DM4, respectively). Control group was injected with NaCl 0.9%. Serum glucose level and proteinuria score were assessed, furthermore tubular injury score was quantified based on Periodic-Acid Schiff (PAS) staining. Reverse Transcriptase-PCR (RT-PCR) was carried out for NGAL, Megalin, Cubilin, m-TOR, Bax, and BASP-1 mRNA expression. Data were analyzed using SPSS 22 software.

RESULTS: DM led to kidney injury in this model with significant higher glucose level, proteinuria and tubular injury, especially in DM4 group which represented chronic phase of DN and CKD. These findings associated with upregulation of Megalin,Cubilin and NGAL mRNA expression in DM groups, especially in DM4 group. DM4 group also revealed higher expression of Bax, BASP and mTOR mRNA expression which demonstrated apoptosis.

METHODS AND MATERIALS: Hyperuricemia model was performed in male Swiss Webster mice. Intraperitoneally injection of uric acid (125mg/kg body weight) was done for 7 and 14 days (UA7 and UA14 groups). Meanwhile, the UAL groups were injected with uric acid and followed by the administration of allopurinol (UAL7 and UAL14 groups). On the due date, mice were sacrificed, and liver was harvested. Uric acid, SGOT, SGPT, and albumin level were measured from the serum. The mRNA expression of TLR4, MCP1, CD68, and collagen1 were assessed through RT-PCR. Liver fibrosis was quantified through Sirius red staining, while the number of hepatic stellates cells (HSCs) and TLR4 were assessed through IHC staining.

RESULTS: Uric acid induction for 7 and 14 days stimulated an increase of both SGOT and SGPT serum levels. Followed by enhanced inflammatory mediators: Toll-like receptor-4 (TLR- 4), Monocyte Chemoattractant Protein-1 (MCP-1) and Cluster of Differentiation 68 (CD68) mRNA expression in the liver (p<0.05). The histological findings showed that the UA7 and UA14 groups had higher liver fibrosis scores (p<0.05), collagen I mRNA expression (p<0.05), and the number of HSCs (p<0.05) compared to Control group. Administration of allopurinol showed amelioration of uric acid and liver enzymes levels which followed by inflammatory mediators, liver fibrosis and collagen1, and hepatic stellate cells significantly.

METHODS: Mice were divided into three groups: sham operation (SO, n = 6), 5/6 SN for seven days (SN7, n = 7) and SN7 with oral CeA treatment (SN7-CeA, n = 7). At day 7, mice were euthanised, kidneys were harvested and stained with periodic-acid Schiff (for tubular injury and glomerulosclerosis) and sirius red (for fibrosis and vascular remodeling) staining. mRNA expression of prepro-endothelin-1, nephrin, E-cadherin, bone morphogenic protein-7 (BMP-7), toll-like receptor 4 (TLR4), tumour necrosis factor-α (TNFα) and hepatocyte growth factor (HGF) were quantified using reverse transcriptase-PCR.

RESULTS: SN group demonstrated significant higher interstitial fibrosis, vascular remodeling, tubular injury and glomerulosclerosis (P < 0.01) compared to SO group. Meanwhile, in SN7-CeA demonstrated attenuation of vascular remodeling as shown by significant higher lumen area with lower Wall/Lumen area ratio compared to SN7. RT-PCR analysis showed up-regulation of nephrin, BMP-7 and E-cadherin mRNA expression (P < 0.05) and down-regulation of ppET-1 in SN7-CeA group compared to SN7 group (P < 0.05).

METHODS: Intraperitoneal injection of streptozotocin (STZ) was used to induce diabetes in rats at a single dose (60 mg/kg body weight [BW]). Rats were euthanised at 1 month (DM1 group), 2 months (DM2 group) and 4 months (DM4 group) following diabetes induction with six rats in each group. Immunohistochemistry was performed against SOD1, CD68, p53 and p16 antibodies. Messenger RNA (mRNA) expressions of SOD1, SOD2, GPx, CD68, p53, p21 and caspase-3 genes were measured by reverse transcription-polymerase chain reaction.

RESULTS: Hepatic p53 mRNA expression was significantly higher in DM1, DM2 and DM4 groups compared to the control group. The p21 and caspase-3 mRNA expressions were significantly upregulated in the DM2 and DM4 groups. The p16-positive cells were obviously increased, particularly in the DM4 group. Bivariate correlation analysis showed mRNA expressions of p21 and caspase-3 genes were positively correlated with the p53 gene.