Possible Protective Effect of TNF-α Inhibition and Triad NO/cGMP/VEGF Activation on Gastric Ulcer in Rats

Author(s):  
Ekram Nemr Abd Al Haleem ◽  
Fatma Ibrahim ◽  
Sawsan A. Zaitone ◽  
Hossam El-Deen Arafa

A peptic ulcer is one of the world's major gastrointestinal disorders, embracing both gastric and duodenal ulcers, and affecting 10% of the world population. The current study aimed to investigate the possible protective effect of tadalafil and pentoxifylline on indomethacin-induced peptic ulcers. Male albino rats were divided into five groups. Control group, ulcerated group. Indomethacin+ Tadalafil, in which animals were pretreated with tadalafil orally before indomethacin. Indomethacin+ PTX, in which animals were pretreated with PTX orally before indomethacin. Indomethacin + combination of two drugs. Indomethacin revealed histopathological changes, ulcer scoring, and ulcer index were markedly increased. Serum levels of PGE2 and HO-1 were significantly decreased. The ulcerogenic also induced marked oxidative stress as evident from the increased MDA, decreased in gastric GSH content and SOD activity, while the gastric MPO was increased. Gastric NO content was decreased and the expression of VEGF was downregulated while the TNF-a level was dramatically increased. Pretreatment of the ulcerative group by either tadalafil or pentoxifylline or their combination improved all these pathological changes. Tadalafil or PTX may have a role in protecting gastric mucosa damage caused by indomethacin which may be useful in the future for the treatment of gastric ulceration.

2021 ◽  
Author(s):  
Ahmed S. Alazzouni ◽  
Mohamed Abdel Daim ◽  
Mohamed S. Gabri ◽  
Aya S. Fathalla ◽  
Ashraf Albrakati ◽  
...  

Abstract Background: Pomegranate peel extract (PPE) is known to possess bioactive compounds such as phenolics and flavonoids, considered among the more potent antioxidants and anti-inflammatory sources.Aims: This study was designed to evaluate PPE activity's protective effect as a natural therapeutic against peptic ulcers induced by Brexin.Methods: 40 rats were divided into four groups: Control group: ten rats received normal saline treatment; Brexit group: ten rats received a single oral dose of Brexit to induce the stomach ulcer; Antodine group: ten rats received Antodine (50 mg/kg) as a commercial drug for the peptic ulcer treatment once for two weeks following a peptic ulcer; Pomegranate group: ten rats of the group received PPE (43 mg/kg) treatments. Histological, histochemical, immunohistochemical techniques were used to detect histopathological damages in stomach rats in all groups.Results: The histopathological results showed that PPE treatments following Brexin-induced peptic ulcer ameliorated histological degenerative changes in the gastric glandular. Chief and surface mucous cells that are lining gastric mucosa were regained when compared with the other groups. The histochemical results showed that PPE treatment following ulcer provided an improvement in the secretion and distribution of the polysaccharides in the epithelial cells when compared with the other groups. Also, immunohistochemical results indicated a significant decrease in immunoreactivity of cytokeratin-20, cyclooxygenase-2, and proliferating cell nuclear antigen (PCNA) in epithelial cells of rats in ulcer-model when compared with the other groups.Conclusion: PPE revealed its antiulcer activity and is recommended as a natural remedy against gastric mucosal injury induced by Brexin.


2021 ◽  
Author(s):  
Kani Bilginaylar ◽  
Asli Aykac ◽  
Serkan Sayiner ◽  
Hanife Özkayalar ◽  
Ahmet Özer Şehirli

Abstract I. Background: Methotrexate (MTX), a chemotherapeutic agent, is known to cause oral mucositis. Chitosan has been shown to have a protective effect in inflammatory animal models. This research aimed to examine the protective effect of chitosan against oral mucositis caused by MTX. II. Methods and Results: Wistar albino rats were randomly divided into three groups, 8 in each group as follow: Control (saline via oral gavage for 5 days), MTX (60 mg/kg single dose MTX intraperitoneally on 1st day and for following 4 days saline via oral gavage), and MTX+Chitosan(1st day single dose 60 mg/kg MTX intraperitoneally and followed with 200 mg/kg Chitosan via oral gavage for 4 days). After 24 hours of the last dose, animals were euthanised. Blood, tongue, buccal and palatal mucosa tissues were collected. Serum interleukin 1-beta (IL1-β), tumour necrosis factor-alpha (TNF-α), matrix metalloproteinase (MMP-1, and MMP-2) activities, and tissue bcl-2/bax ratio and the expression of caspase-3 (casp-3), and casp-9 were detected. The tissues were also examined histologically. Serum TNF-α, IL1-β, MMP-1 and MMP-2 activities and tissue casp-3 and casp-9 activities significantly increased but the bcl-2/bax ratio significantly decreased in the MTX group compared to the control group. Histologically, diffuse inflammatory cells were observed in MTX group. However, In the MTX + Chitosan group, all parameters approached the values of control group. III. Conclusion: Chitosan has been found to have a protective effect against oral mucosal damage caused by MTX. Thus, it may be a candidate agent against MTX induced oral mucositis.


2020 ◽  
Vol 19 (7) ◽  
pp. 1465-1471
Author(s):  
Osama Abdelaziz Hassan ◽  
Entesar Farghally Amin ◽  
Rabab Ahmed Moussa

Purpose: To study the possible mitigating effect of erdosteine (ERD) against methotrexate (MTX)-induced liver toxicity.Methods: Male albino Sprague-Dawley rats were randomly assigned to four groups of 8 rats each, viz, vehicle control, MTX (20 mg/kg i.p.), MTX (20 mg/kg i.p.) + ERD (300 mg/kg) and ERD (300 mg/kg) groups. Serum levels of alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were determined by enzymatic colorimetric commercial kits while Hepatic tissue content of malondialdehyde (MDA), reduced glutathione (GSH), SOD and catalase (CAT) were also evaluated. In addition, measurement of the inflammatory cytokine, TNF-α, as well as histopathological  examination and histochemical assessment were carried out.Results: The results indicate that, compared to the control group, MTX group showed a remarkable elevation in oxidative stress as indicated by significantly lower levels of SOD, CAT and reduced glutathione, and increased tissue malondialdehyde (p < 0.05). MTX group exhibited significantly higher blood activities of ALT, AST and TNF-α, reflective of hepatocyte damage and inflammation (p < 0.05). In MTX group, significant hepatic degenerative changes were detected on histological examination, while marked apoptotic alternations were observed following  immunohistochemical analysis of caspase-3 expression, when compared to control group. However, administration of ERD to rats ameliorated thechanges in these parameters (p < 0.05).Conclusion: Treatment with ERD in rats produced alleviation in hepatic oxidative stress, apoptosis, inflammation, and histological damage, when compared to MTX group. This study is the first to demonstrate the potentially protective effect of ERD-pretreatment against hepatotoxicity associated with MTX. Keywords: Erdosteine, Methotrexate, Hepatotoxicity, Oxidant, Anti-oxidant                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            


2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Dogan Atilgan ◽  
Bekir S. Parlaktas ◽  
Nihat Uluocak ◽  
Fikret Erdemir ◽  
Sahin Kilic ◽  
...  

Aim. We aimed to evaluate the antioxidant effects of weight loss and melatonin on the obesity-induced oxidative damage in rat testes.Materials and Methods. 28 male Wistar albino rats were randomly divided into 4 groups, each consisting of 7 rats: control group (Group 1), obesity group (Group 2), obesity + MLT group (Group 3), and weight loss group (Group 4). Rats were weighed at the beginning and at the end of the study. Bilateral orchiectomy was performed and 5 cc blood samples were obtained from all of the rats. Superoxide dismutase (SOD), malondialdehyde (MDA), and protein carbonyl (PC) levels were analysed in the testicular tissues and serum. Spermatogenesis was evaluated with the Johnsen scoring system.Results. The testicular tissue and serum levels of MDA, PC, and SOD activity were increased in the obesity group in comparison to the sham operated group (P<0.05). Weight loss and melatonin treatment ameliorated MDA, PC, and SOD levels in testicular tissue and serum significantly (P<0.05). There was no significant difference between groups in terms of mean Johnsen score (P=0.727).Conclusion. Experimentally created obesity caused oxidative stress and both melatonin and weight loss reduced oxidative stress parameters in rat testes.


2018 ◽  
Vol 43 (10) ◽  
pp. 1010-1018 ◽  
Author(s):  
Neven M. Aziz ◽  
Maha Y. Kamel ◽  
Manar S. Mohamed ◽  
Sabreen M. Ahmed

One of the major obstacles that males with diabetes may confront is subfertility or infertility. Thus, the present study investigated the effect of co-administration of metformin and zinc (Zn) on the testes of streptozotocin-induced diabetic rats. Male albino rats were randomly divided into 4 groups: control group; untreated diabetic group; diabetic + metformin group, in which diabetic rats were treated orally with metformin (250 mg/kg) once daily for 4 weeks; and diabetic + metformin + Zn group, in which diabetic rats were treated orally with metformin in combination with Zn (10 mg/kg) once daily for 4 weeks. Concomitant administration of metformin and Zn produced a significant decrease in serum levels of glucose and insulin and testicular levels of malondialdehyde and tumor necrosis factor α. Additionally, there was a significant increase in serum levels of Zn, testosterone, and follicle-stimulating hormone, as well as testicular total antioxidant capacity and anti-apoptotic protein Bcl-2, when compared with both the diabetic and metformin-treated diabetic groups. Moreover, co-administration of Zn and metformin significantly improved testicular histopathology, with a significant reduction in percent area of collagen fibers and nuclear factor kappa B (p65) immunoreactivity and a significant increase in seminiferous tubule diameter and connexin 43 immunoreactivity as compared with the diabetic and metformin-treated diabetic groups. In conclusion, the combination of Zn and metformin was an efficacious and safe alternative treatment, as it had superior antihyperglycemic efficacy and provided additional benefits over metformin alone in rats with type 2 diabetes.


2018 ◽  
Vol 38 (5) ◽  
pp. 499-509 ◽  
Author(s):  
H Bouzenna ◽  
N Samout ◽  
S Dhibi ◽  
S Mbarki ◽  
S Akermi ◽  
...  

The present study is planned to examine the antioxidant activity (AA) and the protective effect of the essential oil of Citrus limon (EOC) against aspirin-induced histopathological changes in the brain, lung, and intestine of female rats. For this purpose, 28 albino rats were classified to control group (group C), aspirin group (group A), EOC group (group EOC), and pretreatment with EOC and treated with aspirin group (group EOC + A). The antioxidant activities of EOC were evaluated by three different assays including reducing power, β-carotene, and scavenging of hydrogen peroxide (H2O2). Our results found that EOC represents, respectively (0.064 ± 0.013 and 0.027 ± 00 mg Quer E/100 µL), of flavonoid and flavonol. Then, it exhibited a potential activity of reducing power (at 300 mg/mL, which was found to be 0.82 ± 0.07), β-carotene-linoleic acid (AA% = 69.28 ± 3.5%), and scavenging of H2O2 (IC50 = 0.23 ± 0.008 mg/mL). In vivo, aspirin given to rats at the dose of 600 mg/kg body weight induced histomorphological damage in brain, lung, and intestine. However, our data found that the pretreatment with EOC offered a significant protection against the injury induced by aspirin. It can be concluded that the protective effect of EOC can be due to its antioxidant activities.


2018 ◽  
Vol 96 (6) ◽  
pp. 713-725 ◽  
Author(s):  
Mabrouk Attia Abd Eldaim ◽  
Fatma Mohamed Ibrahim ◽  
Saher Hassan Orabi ◽  
Azza Hassan ◽  
Hesham Saad El Sabagh

In this study, we evaluated the possible mechanisms through which l-carnitine ameliorates the adverse effects from obesity in rats, induced with a high-fat diet (HFD). For this, 56 albino Wister rats were randomly assigned to 7 groups. The control group was fed a basal diet and injected with saline. The second group was fed the basal diet and injected with l-carnitine (200 mg/kg body mass, by intraperitoneal injection; i.p.). The third group were fed the HFD. The fourth group was fed the HFD and injected with l-carnitine (200 mg/kg body mass, i.p.) for 8 weeks. The fifth group was fed the HFD for 10 weeks. The sixth group were fed the HFD for 10 weeks and were also injected with l-carnitine (200 mg/kg body mass, i.p.) during the final 2 weeks. The seventh group was fed the HFD diet for 8 weeks then the basal diet for 2 weeks. The HFD induced significantly increased levels of hyperglycemia, lipid peroxidation, pathological changes, TNF-α and TGF-β1 protein expression in hepatic tissue, food intake, body weight gain, serum levels of total and non-high-density lipoprotein cholesterol, ketone bodies, triacylglycerol, urea, creatinine, AST, and ALT. However, the HFD diet significantly decreased serum levels of high-density lipoprotein (HDL) and hepatic levels of reduced glutathione. l-Carnitine ameliorated the effects of the HFD on the above-mentioned parameters. This study indicated that l-carnitine had protective and curative effects against HFD-induced hepatosteatosis by reducing hepatic oxidative stress and protein expression of TNF-α and TGF-β1.


2020 ◽  
Vol 36 (6) ◽  
pp. 446-453
Author(s):  
Salma Awad Taghyan ◽  
Hend El Messiry ◽  
Medhat Ahmed El Zainy

This study aimed to evaluate the toxic effect of silver nanoparticles (AgNPs) on the parotid glands (PGs) of albino rats histologically and ultrastructurally and assess the possible protective effect of ascorbic acid as an antioxidant. Thirty male albino rats weighing between 150 mg and 200 mg were divided into three groups: the control group (C1) contained 10 rats that received 2 mg/kg (body weight (bw)) of aqueous nitrate buffer by intraperitoneal (IP) injection daily for 28 days; the AgNPs group contained 10 rats that received 2 mg/kg (bw) IP AgNPs daily for 28 days; and the AgNPs-vitamin C group contained 10 albino rats that received 2 mg/kg (bw) AgNPs IP daily for 28 days with oral administration of 100 mg/kg (bw) vitamin C in drinking water daily for 28 days. The PG acinar and ductal cells of the AgNPs group showed signs of toxicity and degeneration characterized as pleomorphic nuclei, binucleation, cytoplasmic vacuolations, and stagnated secretion in the ductal lumen. In addition to degenerated mitochondria, dilated rough endoplasmic reticulum and lysosomes were filled with AgNPs ( p < 0.001). The AgNPs-vitamin C group showed significantly less degenerative changes histologically and ultrastructurally compared to the AgNPs group ( p = 0.002). AgNPs produced significant toxic effects on the PG of albino rats, presumably through the generation of reactive oxygen species and toxic ion release, and administration of vitamin C was shown effective in decreasing these toxic effects.


2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Zehui Jiang ◽  
Jun Zhang ◽  
Yuanan Lu

Objective. To explore the protective effect and mechanism of rosuvastatin on acute renal injury induced by a nonionic hypotonic contrast medium in rats. Methods. Forty-eight healthy adult SD rats were randomly divided into three groups: normal control group (NC); contrast medium control group (CM); and rosuvastatin intervention group (RI). The RI group was intragastrically administered with a 10 mg/kg of rosuvastatin 12 h prior to the contrast exposure. All rats in CM and RI groups were inoculated with 10 mL/kg of chemical (IV) while the same volume of saline for the NC group. At 24 h and 72 h posttreatments, pathomorphological changes of renal tubules were documented, respectively, and several biochemical indicators were tested to assess renal injury of experimental rats. Results. Compared with the CM group, rats in the RI group showed significantly reduced injury of kidneys and decreased levels of biochemical indicators such as blood Scr, blood Cys-C, urine NAG, urine α1-MG, and urine mALB. The serum Hs-CRP in the CM group increased significantly from 24 h to 72 h (p<0.05), but this was not observed in the rats of the RI group. In addition, SOD activity in the RI group was significantly increased (p<0.01) while SOD activity in renal tissue decreased significantly with time in the CM group (p<0.05). Conclusion. Short-term intervention with rosuvastatin can lead to reduced kidney damage associated with the contrast agent by reducing the levels of inflammatory factors and oxidative stress. Thus, rosuvastatin intervention has a protective effect on rats from contrast-induced nephropathy.


2020 ◽  
Vol 19 (1) ◽  
pp. 121-127
Author(s):  
Ebtisam A. Marzook ◽  
Fawzy A. Marzook ◽  
Ahmed E. Abd El Moneim

Purpose: To evaluate the possible radioprotective effect of Costus speciosus and carnosine as natural antioxidants in order to control the  hyperglycemia developed in male albino rats exposed to acute oxidative stress induced by gamma radiation. Methods: Twenty-eight adult male albino rats were divided into four groups. The first group was taken as a control group, while the three other groups were exposed to Ɣ irradiation at a single 7.5 Gy dose. Furthermore, the rats in the second and third groups were i.p. injected with Costus speciosus root powder and carnosine, respectively. On the 3rd day, after irradiation, the serum levels of glucose, insulin, C peptide, copper, iron, calcium, total antioxidant capacity (TAC) and malondialdehyde (MDA) were measureded. Results: The results revealed that exposure to Ɣ irradiation induced significant increases in serum glucose, iron, and malondialdehyde. However, the levels of serum calcium, copper, total antioxidant capacity and insulin significantly decreased (p < 0.05). A significant decrease was observed in Cpeptide in the exposed group, compared to control group. All the test parameters indicate improvement after treatment with Costus speciosus and carnosine (p < 0.05). Conclusion: Costus speciosus and carnosine ameliorate the effect of gamma radiation, indicating their role as antidiabetic agents and  radioprotectors; however, Costus speciosus was critically more efficient than carnosine. Keywords: Costus speciosus, Carnosine, Diabetes, Insulin, Gamma radiation protection


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