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Inflammation and fibrosis are two pathological features of chronic kidney disease (CKD). Renal fibrosis is considered to be one of the most important conditions, as it may be the result of excessive extracellular matrix protein production and deposition, or prolonged exposure to nephrotoxic substances or drugs. Unfortunately, no suitable therapies or medications are currently available to prevent renal fibrosis. We conducted this study for the evaluation of the protective potential of vanillin by reversing TAA (250 mg/kg TAA for 6 weeks) induced renal injury in rats. The concentrations of the proteins tumour necrosis factor alpha (TNFα), interleukin-6 (IL-6), extracellular signal regulated kinase 1/2 (Erk1/2), and transforming growth factor beta-1 (TGF-β1) in kidney tissues were assessed using ELISA. Kidney Injury Molecule-1 (KIM-1) and mothers against decapentaplegic homologue 2, 3 (SMAD 2, 3) expressions were evaluated using real time PCR. We also estimated the expression of α-smooth muscle actin (α-SMA) using immunohistochemistry. Treatment with vanillin (100 mg/kg) significantly ameliorated kidney Injury and improved the kidney function. Vanillin treatment also significantly decreased the malondialdehyde (MDA) content, and elevated glutathione peroxidase (GPx) and catalase (CAT) activities in kidney tissues. Vanillin also reduced α-SMA renal expression and TNFα, IL-6, TGF-β1, and Erk1/2 renal levels. Vanillin significantly decreased the expression of the genes encoding KIM-1 and SMAD 2, 3 and ameliorated histological abnormalities in kidney architecture. Our molecular docking findings showed that vanillin has a good binding mode inside TGF-β type I receptors (ALK5) biding site.

Liver fibrosis is a significant health problem that can cause serious illness and death. Unfortunately, a standard treatment for liver fibrosis has not been approved yet due to its complicated pathogenesis. The current study aimed at assessing the anti-fibrotic effect of taurine against thioacetamide induced liver fibrosis in rats through the modulation of toll like receptor 4/nuclear factor kappa B signaling pathway. Both concomitant and late taurine treatment (100 mg/kg, IP, daily) significantly reduced the rise in serum ALT and AST activities and significantly reversed the decrease in serum albumin and total protein. These results were confirmed by histopathological examinations and immunehistochemical inspection of α-SMA, caspase-3 and NF-κB. The antioxidant potential of taurine was verified by a marked increase of GSH content and a reduction of MDA level in liver tissue. The anti-fibrotic effects of taurine were evaluated by investigating the expression of TLR4, NF-κB. The protein levels of IL-6, LPS, MyD88, MD2, CD14, TGF-β1 and TNF-α were determined. Docking studies were carried out to understand how taurine interacts inside TLR4-MD2 complex and it showed good binding with the hydrophobic binding site of MD2. We concluded that the anti-fibrotic effect of taurine was attributable to the modulation of the TLR4/NF-κB signaling.

Alpha-lipoic acid (α-LA) is characterized by its unpleasant odor, poor bioavailability and stability. Nanotechnology was applied to overcome this limitation. So we aimed in this study to formulate α-LA in two different forms of chitosan nanoparticles (CsNPs) and solid lipid nanoparticles (SLNPs) and characterize them in terms of physical properties and biological activities against aluminum chloride (AlCl3)-induced neurotoxicity in rats. The vivo study was processed on 50 rats divided into 5 groups as follow: control, neurotoxic, treated α-LA, treated α-lipoic acid-loaded chitosan nanoparticles (α-LA-CsNPs) and treated α-lipoic acid-loaded solid lipid nanoparticles (α-LA-SLNPs) groups. The result was depicted by transmission electron microscopy (TEM) revealed that α-LA-SLNPs had a regular spherical shape while α-LA-CsNPs showed an irregular spherical form. Dynamic light scattering (DLS) analysis showed that the average particle size for α-LA-SLNPs was about 71 nm and for α-LA-CsNPs was about 126 nm. After the experimental period, we observed that AlCl3 administration significantly increased oxidative stress, neuroinflammation and apoptosis and decreased brain fatty acid contentsand brain-derived neurotrophic factor,while α-LA, α-LA-CsNPs and α-LA-SLNPs were able to ameliorate these negative changes in the neurotoxic rats. However, the effect of the α-LA-loaded NPs was more prominent than that of pristine α-LA but the α-LA-SLNPs group was almost close to the control group. Conclusion: α-LA can attenuate neurotoxicity induced by AlCl3, attributed to its anti-inflammatory, antioxidant and anti-apoptotic activities in addition to the effectiveness of the encapsulation technique that can increase the efficiency and stability of α-LA. Moreover, α-LA-SLNPs are more efficient than α-LA-CsNPs.

This study investigated the molecular mechanisms by which taurine exerts its reno-protective effects in thioacetamide (TAA) – induced kidney injury in rats. Rats received taurine (100 mg/kg daily, intraperitoneally) either from day 1 of TAA injection (250 mg/kg twice weekly for 6 weeks) or after 6 weeks of TAA administration. Taurine treatment, either concomitant or later as a therapy, restored kidney functions, reduced blood urea nitrogen (BUN), creatinine, and malondialdehyde (MDA), increased renal levels of superoxide dismutase (SOD), and reversed the increase of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase–associated lipocalin (NGAL) caused by TAA. Taurine treatment also led to a significant rise in nuclear factor erythroid 2–related factor 2 (Nrf2), hemoxygenase-1 (HO-1), and NADPH quinone oxidoreductase-1 (NQO-1) levels, with significant suppression of extracellular signal-regulated kinase (ERK) 1/2, nuclear factor kappa B (NF-κB), and tumor necrosis factor α (TNF-α) gene expressions, and interleukin-18 (IL-18) and TNF-α protein levels compared with those in TAA kidney-injured rats. Taurine exhibited reno-protective potential in TAA-induced kidney injury through its antioxidant and anti-inflammatory effects. Taurine antioxidant activity is accredited for its effect on Nrf-2 induction and subsequent activation of HO-1 and NQO-1. In addition, taurine exerts its anti-inflammatory effect via regulating NF-κB transcription and subsequent production of pro-inflammatory mediators via mitogen-activated protein kinase (MAPK) signaling regulation.

This study has been designed to investigate the role of vanillin either as prophylaxis or treatment in liver regeneration augmentation and liver fibrosis regression in thioacetamide (TAA) induced liver damage.Animals were injected with TAA to induce liver injury (200mg/kg twice weekly) for 8 weeks. In vanillin prophylaxis group; rats were administered vanillin (100 mg/Kg; IP, daily) from day 1 of TAA injection for 8 weeks. In vanillin treatment group; rats were confronted with the same dose of TAA injection for 8 weeks then treated with vanillin (100 mg/Kg, IP, daily) for 4 weeks. ALT, AST activities, serum albumin, hepatic GSH, MDA, HGF, VEGF, IL-6 and TNF-α levels were measured and also, MMP-2, TIMP-1 and cyclin D gene expression were determined. Liver sections were stained with HE and Sirius red and immunostained for Ki-67 and α-SMA for histological and immunohistological changes analysis.Vanillin improved liver function and histology. Also, showed a remarkable increase in hepatic HGF and VEGF level, and up-regulation of cyclin D1 expression accompanied by a significant up-regulation of MMP-2 and down- regulation of TIMP-1. All these effects were accompanied by TNF-α, IL-6 and oxidative stress significant attenuation.In conclusion, vanillin enhanced liver regeneration in TAA induced liver damage model; targeting growth factors (HGF, VEGF) and cellular proliferation marker cyclin D1. As well as stimulating fibrosis regression by inhibition of ECM accumulation and enhancing its degradation.

This study aims to investigate the potential synergistic effect of the combined treatment of galloylquinic acid compounds from Copaifera lucens with doxorubicin via the modulation of the Notch pathway in solid Ehrlich carcinoma-bearing mice model.The solid tumor model was induced by subcutaneous inoculation of Ehrlich carcinoma cells in the right hind limb of mice, after serial syngeneic cell passages in the peritoneal cavity. Sixty mice were allocated into five groups including treated groups with galloylquinic acid compounds, doxorubicin, and their combination. Normal and tumor control groups were also assigned. Tissue homogenates were collected to measure the levels of the Notch-1, Hes-1, Jagged-1, TNF-α, IL-6 and VEGF, as well as SOD, MDA, and GSH. Histopathological and immunohistochemical examinations of tumor or control tissues were also performed for the levels of NF-κB p65, cyclin D1 and caspase 3 activity.Our results showed that the combined treatment of galloylquinic acid compounds with doxorubicin significantly decreased the levels of the Notch-1, Hes-1, Jagged-1, TNF-α, IL-6, VEGF, NF-κB p65, and cyclin D1 in tumor tissues. Moreover, the compounds induced cancer cell death as evidence by increasing the caspase 3 activity, and they possessed potent inhibitory effects on oxidative stress.Galloylquinic acid compounds exhibited promising antineoplastic effects and promoted the chemosensitivity of doxorubicin, mainly by modulating the Notch signaling pathway and its downstream effectors. These compounds may be considered in solid tumors treatment for improving the efficacy and reducing the side effects of chemotherapeutic agents.

Aim of work The study was conducted for evaluation of the antitumor activity of SSTN92-119 against HCC induced by thioacetamide in rats. Methods Sixty male Sprague-Dawley rats were randomized into four equal groups: Control, SSTN92-119, HCC, and HCC + SSTN92-119. Liver function tests were measured in serum. Liver homogenate was used for determination of: i) integrinαѴβ3 (ITGαѴβ3), insulin like growth factor-1 receptor (IGF-1R), vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2) and alpha-fetoprotein (AFP) levels by ELISA, ii) syndecan-1 (CD-138), IGF-1R and VEGF genes expressions by qRT-PCR, iii) MDA, NO, GSH concentrations and SOD activity. Histopathological and immunohistochemical examination of liver tissue was performed. Results SSTN92-119 decreased HCC-induced elevation in ALT, AST, ALP and GGT activities and reversed HCC-induced reduction in total protein and albumin concentrations significantly. SSTN92-119 significantly elevated hepatic SOD and GSH and reduced both NO and MDA levels. Protein levels of ITGαѴβ3, IGF-1R, VEGF, FGF-2 and AFP were decreased in HCC- SSTN92-119 group as well as gene expression of CD-138, IGF-1R and VEGF compared with HCC group. Conclusions SSTN92-119 down regulates ITGαѴβ3 receptor and subsequently reduces the activation of angiogenic growth factors VEGF and FGF-2. Therefore, SSTN92-119 is becoming a promising anti-integrin αѴβ3 that inhibits angiogenesis and proliferation in HCC.

Syndecan-1 is a trans-membrane heparan sulfate proteoglycan that localizes in epithelial cells and has been shown to be present in normal hepatocytes. It is thought to be involved in processes such as cell growth, differentiation and adhesion. However, the clinical data regarding syndecan-1 in patients with hepatocellular carcinoma (HCC) are scarce and controversial. Therefore, we need to evaluate the effects of HCC on the serum levels of syndecan-1. Thus, 40 patients with HCC and 31 patients with liver cirrhosis were physically examined. Blood samples were taken for measurements of routine markers (sGPT, sGOT, bilirubin, albumin, and α-fetoprotein), as well as serum levels of interleukin (IL)-6 and syndecan-1. Patients with liver cirrhosis showed significant increase in serum IL-6 as compared with HCC patients and the control subjects. Serum level of syndecan-1 was significantly increased in HCC patients as compared with the cirrhotic and control groups. In addition, significant positive correlations between syndecan-1 and serum levels of ALT, AST in HCC patients were found. Moreover, syndecan-1 increased significantly with increasing stage of Barcelona-Clinic Liver Cancer Group diagnostic and treatment strategy. In conclusion, the development of HCC is accompanied by a significant elevation in serum syndecan-1 levels. The increase in serum syndecan-1 may be linked with progression of HCC.