Publications by authors named "Amal M H Ghanim"

7 Publications

  • Page 1 of 1

Vanillin augments liver regeneration effectively in hioacetamide induced liver fibrosis rat model.

Life Sci 2021 Oct 9;286:120036. Epub 2021 Oct 9.

Department of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt; Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Alexandria University, Alexandria 21500, Egypt. Electronic address:

Aims: 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.

Materials And Methods: 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 H&E and Sirius red and immunostained for Ki-67 and α-SMA for histological and immunohistological changes analysis.

Key Findings: 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.

Significance: 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.
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http://dx.doi.org/10.1016/j.lfs.2021.120036DOI Listing
October 2021

Taurine ameliorates thioacetamide induced liver fibrosis in rats via modulation of toll like receptor 4/nuclear factor kappa B signaling pathway.

Sci Rep 2021 06 10;11(1):12296. Epub 2021 Jun 10.

Department of Biochemistry, Faculty of Pharmacy, Delta University, Gamasa, 35712, Egypt.

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.
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http://dx.doi.org/10.1038/s41598-021-91666-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192756PMC
June 2021

Ganoderma lucidum ameliorates the diabetic nephropathy via down-regulatory effect on TGFβ-1 and TLR-4/NFκB signalling pathways.

J Pharm Pharmacol 2021 Aug;73(9):1250-1261

Department of Biochemistry, Faculty of Pharmacy, Fayoum University, Fayoum, Egypt.

Objectives: Diabetic nephropathy (DN) is one of the most important complications of diabetes mellitus and it is considered as a principal cause for end-stage renal failure. Ganoderma lucidum (GL) has been studied for its reno-protective effect against different kidney injury models. The aim of our study is to investigate the mechanisms by which GL can improve kidney injury and consequent renal inflammation and fibrosis.

Methods: GL either in a low dose (250 mg/kg, i.p.) or high dose (500 mg/kg, i.p.) was administered to DN rat model, and nephropathy indices were investigated.

Key Findings: GL treatment significantly down-regulated kidney injury molecule-1 (KIM-1) gene expression and inhibited TLR-4 (Toll-like receptor-4)/NFκB (nuclear factor kappa B) signalling pathway. As well, GL treatment significantly decreased the pro-inflammatory mediator; IL-1β (interleukin-1 beta) level and fibrosis-associated growth factors; FGF-23 (fibroblast growth factor-23) and TGFβ-1 (transforming growth factor beta-1) levels. In addition, GL remarkably inhibited (Bax) the pro-apoptotic protein and induced (Bcl-2) the anti-apoptotic protein expression in kidneys. Moreover, GL treatment significantly alleviates kidney injury indicated by correcting the deteriorated kidney function and improving oxidative stress status in DN rats.

Conclusions: GL significantly improved renal function indices through dose-dependent kidney function restoration, oxidative stress reduction, down-regulation of gene expression of KIM-1 and TLR4/NFκB signalling pathway blockage with subsequent alleviation of renal inflammation and fibrosis.
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http://dx.doi.org/10.1093/jpp/rgab058DOI Listing
August 2021

Novel complementary antitumour effects of celastrol and metformin by targeting IκBκB, apoptosis and NLRP3 inflammasome activation in diethylnitrosamine-induced murine hepatocarcinogenesis.

Cancer Chemother Pharmacol 2020 02 27;85(2):331-343. Epub 2020 Jan 27.

Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, International Coastal Road, Gamasa City, P.O. Box: +11152, Mansoura, Dakahlia, Egypt.

One promising strategy for minimizing chemotherapeutic resistance in hepatocellular carcinoma (HCC) is the use of effective chemosensitizers. We studied the complementary multi-targeted molecular mechanisms of metformin and celastrol in mice with diethylnitrosamine-induced HCC to investigate whether metformin could augment the sensitivity of HCC tissue to the effect of celastrol. Simultaneous administration of celastrol (2 mg/kg) and metformin (200 mg/kg) improved liver function, enhanced the histological picture and prolonged survival. Additionally, combination therapy exerted anti-inflammatory activity, as indicated by the decreased levels of TNF-α and IL-6. This protective role could be attributed to inhibition of inflammasome activation. Herein, our data revealed downregulated NLRP3 gene expression, suppressed caspase-1 activity and reduced levels of the active forms of IL-1β and IL-18. Under this condition, pyroptotic activity was suppressed. In contrast, in the celastrol and celastrol + metformin groups, the apoptotic potential was amplified, as revealed by the increase in the caspase-9 and caspase-3 levels and Bax:BCL-2 ratio. In addition to their repressive effect on the gene expression of NFκBp65, TNFR and TLR4, metformin and celastrol inhibited phosphorylation-induced activation of IκBκB and NFκBp65 and decreased IκBα degradation. Combination therapy with metformin and celastrol repressed markers of angiogenesis, metastasis and tumour proliferation, as revealed by the decreased hepatic levels of VEGF, MMP-2/9 and cyclin D1 mRNA, respectively. In conclusion, by inhibiting NLRP3 inflammasome and its prerequisite NFκB signalling, simultaneous administration of metformin and celastrol appears to have additive benefits in the treatment of HCC compared to cela monotherapy. This effect warrants further clinical investigation.
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http://dx.doi.org/10.1007/s00280-020-04033-zDOI Listing
February 2020

Mebendazole augments sensitivity to sorafenib by targeting MAPK and BCL-2 signalling in n-nitrosodiethylamine-induced murine hepatocellular carcinoma.

Sci Rep 2019 12 13;9(1):19095. Epub 2019 Dec 13.

Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt.

Sorafenib (SO) is a multi-kinase inhibitor that targets upstream signals in the MAPK pathway. Drug resistance and transient survival benefits are the main obstacles associated with SO treatment in Hepatocellular carcinoma (HCC) patients. Mebendazole (MBZ), an anthelmintic agent, has demonstrated activity against various cancer types. Therefore, we aimed to investigate the possible mechanisms of MBZ other than its anti-tubulin activity. MBZ (100 mg/kg/day, P.O.) was administered to N-nitrosodiethylamine-induced HCC mice as a monotherapeutic agent or in combination with SO. Our results revealed that MBZ decreased AFP levels, improved liver function and histology and increased survival in HCC mice, particularly when administered in combination with SO. MBZ also reduced hepatic inflammation and fibrogenesis as evidenced by reductions in TNF-α and TGF-β1 levels, respectively. Increased hepatic caspases-3 and -9 and decreased BCL-2 levels suggest induced-cell death. In addition, MBZ demonstrated anti-angiogenic, anti-metastatic, and anti-proliferative effects, as indicated by reduced VEGF levels, MMP-2:TIMP-1 ratios, and reduced cyclin D1 levels and Ki67 immunostaining, respectively. Our main finding was that MBZ targeted downstream signal of the MAPK pathway by inhibiting ERK1/2 phosphorylation. Targeting downstream MAPK signalling by MBZ and upstream signalling by SO is a novel approach to minimizing resistance and prolonging survival.
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http://dx.doi.org/10.1038/s41598-019-55666-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6911098PMC
December 2019

Bone marrow-derived mesenchymal stem cells effectively regenerate fibrotic liver in bile duct ligation rat model.

Exp Biol Med (Maywood) 2016 Mar 24;241(6):581-91. Epub 2016 Jan 24.

Biochemistry Department, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt.

Mesenchymal stem cells (MSCs) have attracted lots of attention for the treatment of acute liver failure and end-stage liver diseases. This study aimed at investigating the fundamental mechanism by which bone marrow-derived MSCs (BM-MSCs) induce liver regeneration of fibrotic liver in rats. Rats underwent bile duct ligation (BDL) surgery and four weeks later they were treated with either BM-MSCs (3 × 10(6) cells /rat, once, tail vein injection) or silymarin (100 mg/kg, daily, orally) for four weeks. Liver function tests and hepatic oxidative stress were determined. Hepatic injury and fibrosis were assessed by H and E, Sirus red staining and immunohistochemical expression of α-smooth muscle actin (α-SMA). Hepatocyte growth factor (HGF) and the gene expression of cytokeratin-19 (CK-19) and matrix metalloproteinase-2 (MMP-2) in liver tissue were determined. BDL induced cholestatic liver injury characterized by elevated ALT and AST activities, bilirubin and decreased albumin. The architecture damage was staged as Metavir score: F3, A3. Fibrosis increased around proliferating bile duct as indicated by sirus red staining and α-SMA immunostaining. Fibrogenesis was favored over fibrolysis and confirmed by decreased HGF with increased expression of CK-19, but decreased MMP-2 expression. BM-MSCs treatment restored deteriorated liver functions and restored the histological changes, resolved fibrosis by improving liver regenerative capabilities (P < 0.001), increases in HGF and MMP-2 mRNA and downregulating CK-19 mRNA. Sliymarin, however, induced similar but less prominent effects compared to BM-MSCs. In conclusion, liver regenerative capabilities can be stimulated by BM-MSCs via augmentation of HGF that subsequently up-regulate MMP-2 mRNA while downregulating CK-19 mRNA.
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http://dx.doi.org/10.1177/1535370215627219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4950332PMC
March 2016

Effect of erythropoietin therapy on the progression of cisplatin induced renal injury in rats.

Exp Toxicol Pathol 2013 Jan 15;65(1-2):197-203. Epub 2011 Sep 15.

Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Sharkia Gov., Zagazig 44519, Egypt.

Cisplatin is one of the most important chemotherapeutic agents useful in the treatment of a variety of solid tumors; however, it has several side effects such as nephrotoxicity. In the present study, the effect of rhEPO on acute kidney injury induced by i.p. injection of rats with 9.0 mg/kg cisplatin was studied. It was observed that EPO treated group showed a significantly lower rate in the extent and severity of the histological signs of kidney injury than untreated one. This is attributed to (i) a decrease in the elevated oxidative and nitrosative stress markers, (ii) reduction of the expression of VEGF, HO-1 and iNOS as well as (iii) improvement of Bcl2 immunoreaction in most tubular cells. Thus, EPO may be one of the futures therapeutic possibilities to overcome the side effects of anti-cancer drugs induced acute renal injury through various mechanisms including down regulation of vascular endothelial growth factor (VEGF), hemeoxygenase-1 (HO-1) and inducible nitric oxide synthase (iNOS) expressions in addition to stimulation of tubular cell regeneration.
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http://dx.doi.org/10.1016/j.etp.2011.08.006DOI Listing
January 2013
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