scholarly journals A Novel Role of SIRT1/ FGF-21 in Taurine Protection Against Cafeteria Diet-Induced Steatohepatitis in Rats

2017 ◽  
Vol 43 (2) ◽  
pp. 644-659 ◽  
Author(s):  
Azza H. Abd Elwahab ◽  
Basma K. Ramadan ◽  
Mona F. Schaalan  ◽  
Amina M. Tolba

Background: Non-alcoholic fatty liver disease (NAFLD) is one of the alarmingly rising clinical problems in the 21st century with no effective drug treatment until now. Taurine is an essential amino acid in humans that proved efficacy as a non-pharmacological therapy in a plethora of diseases; however, its impact on NAFLD remains elusive. The aim of the current study is to evaluate the protective mechanism of taurine in experimental steatohepatitis induced by junk food given as cafeteria-diet (CAF-D) in male albino rats. Methods: Forty adult male albino rats of local strain between 8-10 weeks old, weighing 150 ± 20 g, were divided into four equal groups: Group I (control group), Group II (Taurine group), Group III (CAF-D for 12 weeks) and Group IV (CAF-D +Taurine). CAF-D was given in addition to the standard chow for 12 weeks, where each rat was given one piece of beef burger fried in 15 g of sunflower oil, one teaspoonful of mayonnaise, and one piece of petit pan bread, weighing 60g/ piece. In the serum, liver function tests; ALT, AST, ALP, GGT and the lipid profile; TG, TC, HDL-C added to reduced glutathione (GSH) were assessed colorimetrically, while fibroblast growth factor (FGF)-21, adiponectin & interleukin (IL)-6 via ELISA. The same technique was used for the assays of the hepatic levels of FGF-21, silent information regulator (SIRT1), malondialdehyde (MDA),IL-10, tumor necrosis factor-α (TNF-α) as well as the apoptotic markers; caspase-3 and B-cell lymphoma (Bcl-2). Results: The cafeteria-diet induced steatohepatitis was reflected by significantly increased body and liver weight gain, elevation of liver enzymes; ALT, AST, ALP and GGT added to the dyslipidemic panel, presented as increased TC, TG, LDL-C and decreased HDL-C levels. The steatosis-induced inflammatory milieu, marked by elevated serum levels of FGF-21, IL-6, hepatic TNF-α, as well as reduced IL-10 and adiponectin, was associated with steatosis- induced hepatic oxidative stress, reflected by increased hepatic MDA and decreased GSH levels, along with stimulated caspase-3 and decline in BcL-2 hepatic levels. These pathological disturbances were significantly ameliorated by taurine supplementation and evidenced histopathologically. The cross talk between hepatic FGF-21 and SIRT1 and their association to the induced perturbations are novel findings in this study. Taurine's efficacy in restoration of hepatic structure and function is partially via the increase in SIRT1 and associated reduction of FGF-21. Conclusion: The findings of the current study prove the protective role of taurine in NAFLD via a novel role in the amelioration of FGF-21/ SIRT1 axis, which could be considered a new therapeutic target.

Author(s):  
HEBA A. M. MOUSA

Objective: This study aimed to investigate the possible protective effect of rutin in management of TiO2NPs-induced renal injury in mice. Methods: Forty male Swiss albino mice were randomly divided into four groups (n=10). Group (I) served as a control group, group (II) received 100 mg/kg body weight (b. wt) of rutin (orally), group (III) received 70 mg/kg b. wt of TiO2NPs,injected intraperitoneally (i. p.), Group (IV) received 70 mg/kg b. wt of TiO2NPs plus 100 mg/kg b. wt of rutin; for 14 successive days. The renal toxicity was determined through evaluating the renal function biomarkers (serum creatinine, urea, and uric acid) and the levels of malondialdehyde (MDA), reduced glutathion (GSH), nuclear factor kappa B (NF-kB), tumor necrosis factor-α (TNF)-α, B-cell lymphoma (BCL)-2 and caspase-3 in renal tissues. Results: Administration of TiO2NPs plus rutin prevented the deleterious effect of TiO2NPs on mice kidneys through improving the renal functions, and alleviating the increase in MDA, NF-kB, TNF-α, and caspase-3 levels, as well as the decrease in GSH andBCL-2 levels, in renal tissues. Conclusion: Taken together, these findings suggested that rutin plays a role in alleviating TiO2NPs-induced oxidative stress, inflammation, and apoptosis, and exerts renal protective effects.


2011 ◽  
Vol 31 (6) ◽  
pp. 565-573 ◽  
Author(s):  
M Tutanc ◽  
V Arica ◽  
N Yılmaz ◽  
A Nacar ◽  
I Zararsiz ◽  
...  

Aim: In cyclosporin-A (CsA)-induced toxicity, oxidative stress has been implicated as a potential responsible mechanism. Therefore, we aimed to investigate the protective role of erdosteine against CsA-induced nephrotoxicity in terms of tissue oxidant/antioxidant parameters and light microscopy in rats. Materials and methods: Wistar albino rats were randomly separated into four groups. Group 1 rats treated with sodium chloride served as the control, group 2 rats were treated with CsA, group 3 with CsA plus erdosteine, and group 4 with erdosteine alone. Animals were killed and blood samples were analyzed for blood urea nitrogen (BUN), serum creatinine (Cr), uric acid (UA), total protein (TP), and albumin (ALB) levels. Kidney sections were analyzed for malondialdehyde (MDA) and nitric oxide (NO) levels and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities, as well as for histopathological changes. Results: In the CsA group, MDA, GSH-Px, BUN, and Cr levels were increased. The TP and ALB levels were decreased. These changes had been improved by erdosteine administration. Other biochemical parameters did not show any significant change. Conclusion: These results indicate that erdosteine produces a protective mechanism against CsA-induced nephrotoxicity and suggest a role of oxidative stress in pathogenesis.


2020 ◽  
pp. 096032712094745
Author(s):  
Marwa G Ahmed ◽  
Mona El-Demerdash Ibrahim ◽  
Hoda R El Sayed ◽  
Samah M Ahmed

The declining rate of male fertility is a growing concern. Tributyltin (TBT) is a well-known endocrine disruptor (ED), that induces imposex in female gastropods and is widely used in various industrial applications. The aim of this study was to evaluate the toxic effects of TBT on the testes of adult albino rats and the possible role of omega-3. Forty two adult male albino rats were divided into five groups; control group (Group I) and four experimental groups: omega-3 treated group, TBT treated group, TBT & omega-3 treated group and follow up group. At the end of the study, the rats were subjected to biochemical, histological, immunohistochemical staining for Ki-67 and seminal examinations. Our results clarfied that TBT induced a significant decrease in testosterone, FSH, LH and serum glutathione peroxidase levels and a significant increase in the serum Malondialdehyde as compared to the control group. Tributyltin induced disorganization and shrinkage of seminiferous tubules, apoptosis, cellular damage and marked reduction in the germinal epithelium. A significant decrease in the cell proliferation and arrested spermatogenesis were also detected. Seminal analysis of TBT group showed a significant affection of all parameters as compared to other groups. Omega-3 ameliorated all of these hazardous effects. Follow up group still showed toxic effects. In conclusion, TBT has a toxic effect on the testis. Increased testicular oxidative stress, cellular damage and arrest of spermatogenesis with attenuation in antioxidant defenses are all contributing factors. Omega-3 can protect against TBT induced reproductive toxicity.


Biomedicines ◽  
2019 ◽  
Vol 7 (2) ◽  
pp. 39
Author(s):  
Sahar Youssef ◽  
Marwa Salah

Olanzapine is an antipsychotic drug effective in the treatment of stress-associated psychiatric illnesses, but its effect on the spleen remains unclear. Vitamin C is essential for the optimum function of the immune system. We aim to investigate the effect of Olanzapine on spleen structures and to assess the protective effect of vitamin C. Forty adult male albino rats were divided into four groups: group (I), a control; group (II), rats were given vitamin C at 40 mg/kg body weight; group (III), rats were given Olanzapine at 2 mg/kg body weight; and group (IV), rats were given vitamin C and Olanzapine at the same dose of group (II) and group (III) for one month. The hematoxylin and eosin (H&E) of the olanzapine treated group showed focal areas of cellular depletion and a decrease in the size of the white pulp. The red pulp was expanded and showed marked congestion and dilatation of blood sinusoids. Cluster of differentiation 3 (CD3) was significantly reduced, however both tumor necrosis factor alpha (TNF-α), and vascular endothelial growth factor (VEGF) were significantly higher. The administration of vitamin C repaired structural and immunohistochemical changes via increased CD3 and decreased TNF-α and VEGF. Therefore, the oxidative and the inflammatory pathways may be the possible mechanisms underlying olanzapine immunotoxicity. Vitamin C exerted immune modulator and antioxidant effects against olanzapine.


2019 ◽  
Vol 19 (8) ◽  
pp. 1141-1147 ◽  
Author(s):  
Ozlem Ozmen ◽  
Senay Topsakal

Objective: The aim of this study was to examine pancreatic pathology and the prophylactic effects of pregabalin in lipopolysaccharide (LPS) induced sepsis model in aged rats. Methods: Twenty-four female, one-year-old, Wistar Albino rats were assigned to three groups; Group I (control), Group II (study group: 5mg/kg LPS intraperitoneal, single dose) and Group III(treatment group: 5mg/kg LPS+30 mg/kg oral pregabalin one hour before LPS). Animals were sacrificed by exsanguination 6 hours after LPS administration. Blood and pancreatic tissue samples were collected for biochemical, pathological, and immunohistochemical analyses. Results: LPS caused increases in serum amylase and lipase level but led to a reduction in glucose levels. Following histopathological analysis, numerous neutrophil leucocyte infiltrations were observed in vessels and pancreatic tissues. Increased caspase-3 expression was observed in both the endocrine and exocrine pancreas in the LPS group. Similarly, IL-6, caspase-3 (Cas-3), inducible nitric oxide synthase (iNOS), granulocyte colony-stimulating factor (G-CSF) and serum amyloid-A (SAA) expressions were increased by LPS. Pregabalin improved biochemical, histopathological, and immunohistochemical findings. Conclusion: This study showed that LPS causes pathological findings in the pancreas, but pregabalin has ameliorative effects in aged rats with sepsis. Cas-3, IL-6, iNOS, G-CSF, and SAA all play pivotal roles in the pathogenesis of LPS-induced pancreatic damage.


Author(s):  
SABHA E. ELBALLAT ◽  
AL-SHIMAA M. ABAS

Objective: Aspartame (ASP) is one of the most common artificial sweeteners. It has been recorded to be safe by World Health Organization. However, numerous publications have concluded that ASP is a genotoxic and carcinogenic sweetener. Methods: The current study aims to examine the effect of ASP consumption (250 mg/kg body weight/day for 90 d) on some biochemical parameters, oxidative/antioxidative status in different tissues, Tumor Necrosis Factor-α (TNF-α), chromosomal aberration (CA) frequency and mitotic index (MI) percentage in addition to the possible ameliorative role of silymarin (50 mg/kg body weight/day for 90 d) against ASP-induced toxicity in male albino rats. Results: The present results have confirmed that ASP is able to induce significant increase in the blood glucose level, liver, kidney and lipid function tests, Malondialdehyde (MDA) level, serum TNF-α level, frequency of CA and MI%. Meanwhile, Glutathione reduced level (GSH), Glutathione–S-transferase (GST) and catalase activity (CAT) were decreased by ASPadministration. Recovery group showed slight enhancement in all parameters but remained significant as compared to the control group. Co-administration of ASP with silymarin showed greater improvement than the recovery group. Conclusion: Silymarin have an ameliorative role against biochemical oxidative stress, inflammatory changes in blood and different tissues, chromosomal aberrations and MI% induced by ASP administration.


2018 ◽  
Vol 34 (2) ◽  
pp. 110-118 ◽  
Author(s):  
Murat Uysal ◽  
Serhat Karaman

Malathion can be ingested, inhaled, or absorbed through the skin, but acute toxicity is maximized when administered orally. Intravenous lipid emulsion (ILE) treatment is used as a new therapeutic method in cases of systemic toxicity caused by some lipid soluble agents. This study aimed to examine the potential treatment effect of ILE on rat lung tissue in a toxicokinetic model of malathion exposure. Twenty-one adult Wistar albino rats were randomly divided into three equal groups. The groups were organized as group I (control), group II (malathion), and group III (malathion + ILE treatment). Malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were evaluated in lung tissues. Immunohistochemical and Western blot analyses were performed to determine the bax, bcl-2, and caspase-3 expression levels. Tissue GSH-Px and SOD activities were decreased and MDA levels were increased in the malathion group. ILE administration increased GSH-Px and SOD activity and decreased MDA levels compared to the malathion group. Furthermore, expression of bax, bcl-2, and caspase-3 significantly increased in the malathion group, and ILE infusion reduced these expression levels. The present study revealed that acute oral malathion administration increased oxidative stress and apoptosis in the lung tissue of rats. ILE infusion prevented oxidative stress and decreased the deleterious effects of malathion. Taken together, the findings of our study suggest that lipid emulsion infusion has treatment efficacy on malathion-induced lung toxicity.


Author(s):  
Hasan Akduman ◽  
Cuneyt Tayman ◽  
Veli Korkmaz ◽  
Filiz Akduman ◽  
Nurdan D. Fettah ◽  
...  

Objective This study aimed to ascertain the effects of astaxanthin (ASX) in an experimental necrotizing enterocolitis (NEC) model using rat pups. Study Design Forty-two pups born from five Wistar albino rats were randomly divided into three groups as the control group, NEC + placebo (saline), and NEC + ASX. Pups in the NEC + ASX group were given 100 mg/kg/day oral ASX from day 1 to day 4 of the study. Saline of 2 mL/kg was given to the NEC + placebo group. Histopathological, immunohistochemical (caspase-3), and biochemical evaluations including the total antioxidant status (TAS), total oxidant status (TOS), superoxide dismutase (SOD), glutathione (GSH), lipid hydroperoxide (LPO), 8-hydroxydeoxyguanosine (8-OHdG), advanced oxidation protein products (AOPP), myeloperoxidase (MPO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and nuclear factor erythroid 2–related factor 2 (Nfr-2) activities were all performed. Results A better survival rate and weight gain were demonstrated in the NEC + ASX group (p < 0.05). In the histopathological evaluation, the severity of intestinal damage was significantly reduced in the NEC + ASX group, as well as decreased apoptosis (enzyme-linked immunosorbent assay [ELISA] for caspase-3; p = 0.001). The biochemical analyses of intestinal tissue TOS, oxidative stress index (OSI; TOS/TAS), IL-1β, LPO, 8-OHdG, AOPP, caspase-3 (p < 0.001 for all), and TNF-α and MPO (p = 0.001 for both parameters) levels were lower in the NEC + ASX group than in the NEC + placebo group. Nrf-2, TAS, GSH, and SOD levels were higher in the NEC + ASX group than in the NEC + placebo group (p = 0.001, 0.001, <0.001, and 0.01, respectively). Conclusion ASX treatment has been shown to effectively reduce the severity of intestinal damage in NEC due to its antioxidant, anti-inflammatory, and antiapoptotic properties. Key Points


2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Omnia Aly ◽  
Dalia M. Abouelfadl ◽  
Olfat G. Shaker ◽  
Gehan A. Hegazy ◽  
Ahmed M. Fayez ◽  
...  

Abstract Background It has been reported that Moringa oleifera (MO) has different medicinal properties. The aim of this study was to evaluate the hepatoprotective role of Moringa oleifera extract on acetaminophen-induced liver fibrosis in albino rats on a biochemical and histological basis. Forty male albino rats were divided into four groups: group I (control group), healthy rates; group II (acetaminophen group), rates received acetaminophen for induction of liver fibrosis; group III (treated group), liver fibrosis of rates treated with Moringa oleifera extract; and group IV (prophylactic group), rates treated with Moringa oleifera extract before and after induction of liver fibrosis. Serum liver function parameters were quantified using a spectrophotometer, while tumor necrosis factor α (TNF-α) and transformed growth factor beta (TGF- β) in liver tissue homogenate by means of enzyme-linked immunosorbent assay (ELISA), and expression of liver tissue TNF-α and TGF-genes was measured by real-time PCR after extraction and purification. Hepatic tissue was also evaluated under a microscope for histopathological changes. Results Our results showed a significant decrease in liver enzymes, TNF-α, and TGF-β in the treated and prophylactic groups compared to the acetaminophen group, and our biochemical data were consistent with the histopathological findings confirming the hepatoprotective effect of Moringa oleifera extract. Conclusions Biochemical parameters and histopathology results provide evidence that Moringa oleifera ethanolic extract has a great potential to prevent and improve liver damage due to its protective activity.


2020 ◽  
Vol 23 (3) ◽  
Author(s):  
Aseel J Ali ◽  
Jamal N.A. Al-Juboori ◽  
Marwan Al-Nimer

Objective: κ-carrageenan is a food stabilizer agent which has an antiproliferative effect, while vitamin D is a prohormone acts on the nuclear receptor and has a cytotoxic against cancer. This study aimed to show the synergistic effect of using topical κ-carrageenan and oral administration of the vitamin D on the 7, 12-dimethylbenz[a] anthracene (DMBA)-induced oral cancer. Material and Methods: fifty four male albino rats were randomly divided into seven groups: Acetone-treated served as control (Group I), vitamin D (5000UI)-treated (Group II), κ-carrageenan (1%)- treated (Group III), DMBA (0.5%)-treated (Group IV), Acetone, κ-carrageenan and DMBA were administered topically on both cheeks and palate, five times weekly for 12 weeks, while the vitamin D was  administered orally twice weekly for 12 weeks. Groups V, VI, and VII were animals treated with vitamin D, κ-carrageenan, and both vitamin D and κ-carrageenan for 8 weeks after induction of oral cancer. At the end of the study, blood samples were obtained by cardiac puncture for determination of TNF-α and EGFR. Results: In the groups III and IV, serum EGFR showed significant low levels compared with Group I. In the Group VII, serum EGFR showed a significantly (p=0.014) low level compared with Group IV (614.3±69.7 pg/ml versus 882.4±45.6 pg/ml, respectively). Higher percentages of high levels of TNF-α were observed in the Groups VI and VII, while a lower percentage of EGFR was observed in the Group VI. Conclusion: both κ-carrageenan and vitamin D have antiproliferative effect against DMBA-inducing oral cancer by increasing the levels of TNF-α and suppressing the signaling pathway of EGFR. Concomitant using κ-carrageenan and vitamin D reduces the antiproliferative effect of each other. KeywordsOral cancer; 7, 12-dimethylbenz[a] anthracene; Vitamin D; κ-carrageenan; Epidermal growth factor receptor; Tumor necrosis factor-α. 


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