The effects of ursodeoxycholic acid in the management of sepsis-induced cholestasis in rodents

Abstract Background: Cholestasis is a condition in which there is impairment of bile flow from the liver to the small bowel. It is a common complication of bacterial infection and sepsis. Treatment is usually directed towards the eradication of bacterial infection and consequences of sepsis. Ursodeoxycholic acid (UDCA) has been under investigation as a possible therapeutic option for the treatments of sepsis-associated cholestasis.Methods: Sixty male albino rats (weighing 100–150g) were subjected to daily doses of UDCA (100 mg/kg, p.o.) for 10 days before or after lipopolysaccharides (LPS) induction of cholestasis. Then, the following liver enzyme activity was assessed: plasma aspartate transferase (AST), plasma alkaline transferase (ALT), plasma alkaline phosphatase (ALP), total bilirubin (TBIL). Hepatocyte apoptosis and immunomodulatory activity were assessed by flow cytometric analysis. Plasma pro-inflammatory cytokines (TNF-, IL-1 and IL-4) were measured by ELISA. Liver histology changes were assessed by hematoxylin and eosin (H&E) staining.Results: Our results showed that LPS-induced cholestasis resulted in a significant rise in the TBIL and liver enzymes including GGT, ALP, AST, and hepatocytes death. UDCA improves serum liver chemistries and halts bile acid cytotoxicity when it was used either as a treatment or prevention, compared to the LPS group. Moreover, UDCA has immunomodulatory properties: the effect of UDCA on the percentage of natural killer (NK) cells did not change in either the treatment or prevention group when compared to LPS induced cholestasis. However, significant decrease in the CD3 has been found in the treatment group as compared to the LPS group, and an unexpected increase in the prevention group compared to the LPS treated group. UDCA failed to ameliorate the increase in plasma TNF-α concentration in the treatment group. On the other hand, UDCA caused reduction in plasma TNF-α in the prevention group. We also found significant reduction in the liver tissue apoptosis in the UDCA treated groups. Conclusion: Prophylactic treatment and treatment with UDCA appear to exert a beneficial effect against the damaging effect of hydrophobic bile acids by LPS-induced secretary failure. This involved multiple mechanisms of action.

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The Effect of Ursodeoxycholic Acid on Small Intestinal Bacterial Overgrowth in Patients with Functional Dyspepsia: A Pilot Randomized Controlled Trial

Nutrients ◽

10.3390/nu12051410 ◽

2020 ◽

Vol 12 (5) ◽

pp. 1410

Author(s):

Bom-Taeck Kim ◽

Kwang-Min Kim ◽

Kyu-Nam Kim

Keyword(s):

Randomized Controlled Trial ◽

Treatment Group ◽

Ursodeoxycholic Acid ◽

Controlled Trial ◽

Bacterial Overgrowth ◽

Small Intestinal Bacterial Overgrowth ◽

Treated Group ◽

Randomized Controlled ◽

Intestinal Bacterial Overgrowth ◽

Small Intestinal

Functional dyspepsia (FD) is associated with small intestinal bacterial overgrowth (SIBO). Several animal studies have reported that ursodeoxycholic acid (UDCA) has antibacterial and anti-inflammatory effects in the intestine. We hypothesized that UDCA may be effective against dyspeptic symptoms and SIBO in patients with FD. We conducted this randomized controlled trial to investigate the effects of UDCA in FD patients with SIBO. Twenty-four patients diagnosed with FD and SIBO based on lactulose breath test (LBT) were randomly assigned to either a UDCA treatment group or an untreated group. The treatment group received 100 mg of UDCA three times per day for two months; the untreated group was monitored for two months without intervention. After two months in both groups, we reevaluated LBT and FD symptoms using the Nepean dyspepsia index-K. FD symptoms in the UDCA-treated group were significantly reduced after two months compared with baseline and FD symptom scores between the UDCA-treated and untreated groups showed statistically significant differences after two months. In addition, the total methane gas levels for 90 minutes in LBT were significantly decreased after two months compared with baseline in the UDCA-treated group. In this preliminary exploratory study, we found that two months of UDCA treatment resulted in FD symptom improvement and reduced methane values during 90 minutes on the LBT, suggesting that methane-producing SIBO were associated with symptoms of dyspepsia and that UDCA was helpful in these patients. These findings need to be validated via large-scale controlled and well-designed studies.

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Potential Therapeutic Effects of Ursodeoxycholic Acid in Comparison to Ramipril in a Rat model of Diabetic Nephropathy

QJM ◽

10.1093/qjmed/hcab114.003 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Maha Safwat Abd-elrahman Elsheemy ◽

Ahmed Abdel-Salam M Elmelegy ◽

Lobna Fouad Abd Elaziz ◽

Nadia Galal M El hefnawy ◽

Mohammad Mahmoud El shaer ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Er Stress ◽

Ursodeoxycholic Acid ◽

Therapeutic Option ◽

Treated Group ◽

Clinical Feature ◽

Control Group ◽

Therapeutic Effects ◽

Biliary Cirrhosis ◽

Progressive Disorder

Abstract Background & Aim Diabetic nephrectomy (DN) is a chronic progressive disorder that complicates long standing diabetes. Albuminuria is a prominent clinical feature of DN. Ursodeoxycholic acid (UDCA) is a physiologic hydrodrophillic bile acid that is therapeutically used in the treatment of primary biliary cirrhosis. It is known to alleviate endoplasmic reticulum (ER) stress in podocytes. In comparison to Ramipril as a standard ACEI therapy of DN, the present study was designed to investigate the effect of UDCA treatment on DN in association with renal biomarkers changes. Method Four groups of male Wister rats (6 per group) were designed; Normal control group, DN untreated group (High fat diet + STZ injection of 45 mg/kg + uninephrectomy), DN/Ramipril group; (1 mg/kg/d orally for 12 weeks) and DN/UDCA group (40 mg/kg/d orally for 12 weeks). Results DN rats treated with UDCA for 12 weeks exhibited significant decrease in ER stress marker, ATF6 with mean percentage value of 73.8% and improvement of podocyte structural deformities that is accompanied by a significant reduction in albuminuria by mean percentage value of 43.8% comparatively to Ramipril that caused reduction in ATF6 level with mean percentage value of 65.5% and reduction in albuminuria by mean percentage value of 50.2%. The remarkable improvement in metabolic profile and the neutral effect on blood pressure in UDCA treated group could explain the renoprotection at histopathological basis rather than the proved hemodynamic effect of ramipril. Conclusion Participation of ER stressmediated apoptosis in the pathophysiology of diabetic nephropathy make the UDCA a potential therapeutic option or add-on therapy due to its anti-apoptotic property apart from classic metabolic and hemodynamic aspects.

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Metformin and l-glutamine ameliorate pancreatic damage induced by chronic nicotine exposure in adult male albino rats

International Journal of Pharmacology and Toxicology ◽

10.14419/ijpt.v7i2.29937 ◽

2019 ◽

Vol 7 (2) ◽

pp. 44

Author(s):

Eman Abdel-Mohsen Abdel-Aziz ◽

Asmaa Y. A. Hussein ◽

Heba A Elnoury

Keyword(s):

Blood Glucose ◽

Heat Shock ◽

Heat Shock Protein 70 ◽

Plasma Insulin ◽

Insulin Level ◽

Treated Group ◽

Pancreatic Tissue ◽

Albino Rats ◽

Pancreatic Damage ◽

Tnf Α

Nicotine is a major addictive component of tobacco and cigarettes. It is believed to play a major role in the development of many diseases of pancreas including induction of pancreatitis and pancreatic cancer. This study was designed to assess the ameliorative effect of metformin & L-glutamine administered either individually or in combination on pancreatic damage induced by chronic exposure to nicotine. Fifty-six adult male albino rats were divided into 7 weight matched groups of 8 animals per each group and treated once daily for a period of 10 weeks according to the following protocol; group I (normal control): left without intervention ; they were allowed to free access to balanced diet & distilled water for the end of the experiment, group II (metformin treated group; Met): metformin was administrated to normal rats at a dose of (150 mg/kg /day /orally); group III (glutamine group ; LG): in which L-glutamine was given to normal rats at a dose of 500 mg/kg by oral gavage); group IV (diseased non-treated group ;Nicotine) were injected subcutaneously with nicotine (1.5 mg/kg/day after day) to induce pancreatitis; group V (Nicotine +Met), VI (Nicotine +LG) &VII (Nicotine +Met + LG) were treated by (Nicotine +Met, Nicotine +LG & Nicotine +Met + LG respectively) by the same doses and routs described above. At the end of the experiment the following biochemical parameters were measured (fasting blood glucose, plasma insulin level, serum amylase and lipase level, tumor necrosis factor alpha (TNF-α), heat shock protein 70 (HSP70) & reduced glutathione; GSH) to investigate the protective effect of either or both drugs on pancreas. Additionally, histopathological evaluations of pancreatic tissues were assessed. The current study documented the damaging effect of nicotine on pancreas evidenced by significant increase of (blood glucose level due to decrease in plasma insulin level, serum lipase and amylase & TNF-α levels along with significant reduction of GSH in pancreatic tissue & heat shock protein -70. This was accompanied by histopathological alteration in pancreatic tissue. The previously mentioned parameters illustrate partial significant improvement in concomitant administration of individual or both metformin & L glutamine along with nicotine. In conclusion, co- supplementation of metformin and L glutamine documented to be anti-hyperglycemic, antioxidant and anti-inflammatory which can ameliorate the damaging effect of nicotine on pancreas. The combination use of both drugs produces more protective effect than each other alone.

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THE ROLE OF HEPARIN IN TREATMENT OF EXPERIMENTAL PERITONITIS

10.36106/gjra/0800937 ◽

2019 ◽

pp. 1-5

Author(s):

Pradeep Kumar Saxena

Keyword(s):

Single Dose ◽

Survival Rate ◽

Treatment Group ◽

Normal Saline ◽

Adhesion Formation ◽

Treated Group ◽

Repeated Dose ◽

Control Group ◽

Albino Rats ◽

Bowel Loop

Background: To produce peritonitis experimentally in albino rats by creation of a necrotic loop of terminal Ileum. Study of peritonitis and gross changes in peritoniteal cavity and to study the effect of single dose heparin (Anticoagulant) in experimentally produced peritonitis. Also to study and compare the effect of repeated small dosage of heparin in peritonitis. Material and Methods The rats were divided into 6 groups, under the 2 experiments. So each group comprised of 8 rats. The peritonitis was proceduced by Rasto's method, in which the peritonitis was caused by a gangrenous loop of small intestine . two types of experiment were carried out: 1. Experiment 1 : The gangrenous loop which produced peritonitis was excised after 24 hours, normal saline was given in control group,whereas heparin as a single dose and heparin in small repeated dose were given by sub-cutaneous or intraperitoneal route for 3 days. No abdominal toilet or antibiotics were given during the time. The surviving as well as the dead rats during observation period were subjected to laparotomy and detailed pathology of peritoneum was studied. 2. Experiment 2 : In this group the gangrenous loop was not resected after 24 hours and normal saline was given in control group 0.2 ml., or heparin in a single dose 50 I.U. or heparin in small repeated dose 20 I.U. twice a day for three days.All the rats were continuously observed during the post-operative period for evidence of any complications. Results: The peritonitis produced by a necrotic bowel loop was severe & brino-purulent.The formation of inter-mesentric abscess in control group was much more evident than the heparinised rats. The size of inter-mesentric abscess was smaller in treated group of albino rats than in control.The incidence of adhesion formation was much more in control group, than in the heparin group, the adhesion were very less friable and easily breakable. The survival rate in heparin treatment group was 75% to 87.5% as compared to the control group, where the survival rate was 50% only.The mortality in the control group, where the necrotic loop, was not resected was as high as 87.5% and rats died within 8 days after operation whereas the mortality rate in treatment group was low that is, from 50% to 60% only. Conclusion: By comparison and contrast of the results of the difference treatment group, it become evident that survival in the treated group was signicantly better than control group. About the evidence of intra-peritoneal infection, it shows that in treated group clearance of peritonitis was much faster than the control group of albino rats:The number and size of intramesentric abscesses were also smaller in treated group. There was also a little benecial effect on adhesion in heparinised albino rats as compared to control group.So heparin in small repeated doses has denitely a signicant effect on secondary bacterial peritonitis and its subsequent results.

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Assessment of gentamicin and cisplatin-induced kidney damage mediated via necrotic and apoptosis genes in albino rats

BMC Veterinary Research ◽

10.1186/s12917-021-03023-4 ◽

2021 ◽

Vol 17 (1) ◽

Author(s):

Tarek Kamal Abouzed ◽

Eman Abd Elrahman Sherif ◽

Mohamed El Sayed Barakat ◽

Kadry Mohamed Sadek ◽

Adil Aldhahrani ◽

...

Keyword(s):

Low Cost ◽

Treated Group ◽

Kidney Damage ◽

Control Group ◽

Albino Rats ◽

Bacterial Diseases ◽

Tnf Α ◽

Apoptotic Genes ◽

Factor Α ◽

Necrosis Factor

Abstract Background Gentamicin (GM) is a low-cost, low-resistance antibiotic commonly used to treat gram-negative bacterial diseases. Cisplatin (Csp) is a platinum-derived anti-neoplastic agent. This experiment aimed to identify the early signs of gentamicin and cisplatin-induced nephrotoxicity in rats. Thirty Wistar rats were divided into three groups of 10: a control group, which received no treatment; a gentamicin group administered by a dose of (100 mg/kg, IP) for 7 consecutive days, and a cisplatin group was administered intraperitoneal in a dose of (1.5 mg/kg body weight) repeated twice a week for 3 weeks. Results Both experimental groups exhibited increased levels of creatinine, urea, and uric acid, with the cisplatin-treated group showing higher levels than the gentamicin group. Experimental groups also exhibited significantly increased Malondialdehyde (MDA), reduced glutathione (GSH), and glutathione peroxidase (GSH-Px) with more pronounced effects in the cisplatin-treated group. Further, both experimental groups exhibited significant up-regulation of Tumor Necrosis Factor α (TNF-α), caspase-3, and Bax and down regulation of Bcl-2. Conclusion These findings confirm the use of necrotic, apoptotic genes as early biomarkers in the detection of tubular kidney damage. Further, cisplatin was shown to have a greater nephrotoxic effect than gentamicin; therefore, its use should be constrained accordingly when co-administered with gentamicin.

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Assessment of Gentamicin and Cisplatin-Induced Kidney Damage Mediated via Necrotic and Apoptosis Genes in Albino Rats

10.21203/rs.3.rs-272049/v1 ◽

2021 ◽

Author(s):

Mohamed El_Sayed Barakat ◽

Tarek Kamal Abouzed ◽

Eman Abd Elrahman Sherif ◽

Kadry Mohamed Sadek ◽

Adil Aldhahrani ◽

...

Keyword(s):

Low Cost ◽

Treated Group ◽

Kidney Damage ◽

Control Group ◽

Albino Rats ◽

Bacterial Diseases ◽

Tnf Α ◽

Apoptotic Genes ◽

Factor Α ◽

Necrosis Factor

Abstract Background: Gentamycin (GM) is a low-cost, low-resistance antibiotic commonly used to treat gram-negative bacterial diseases. Cisplatin (Csp) is a platinum-derived anti-neoplastic agent. This experiment aimed to identify the early signs of gentamicin and cisplatin-induced nephrotoxicity in rats. 30 Wistar rats were divided into three groups of 10: a control group, which received no treatment; a gentamicin group administered by a dose of (100 mg/kg, IP) for 7 consecutive days, and a cisplatin group was administered intraperitoneal in a dose of (1.5mg/kg body weight) repeated twice a week for 3weeks. Results: Both experimental groups exhibited increased levels of creatinine, urea, and uric acid, with the cisplatin-treated group showing higher levels than the gentamicin group. Experimental groups also exhibited significantly increased malondialdehyde (MDA), reduced glutathione (GSH), and glutathione peroxidase (GSH-Px) with more pronounced effects in the cisplatin-treated group. Further, both experimental groups exhibited significant up-regulation of Tumor Necrosis Factor α (TNF-α), caspase-3, and Bax and downregulation of Bcl-2. Conclusion: These findings confirm the use of necrotic, apoptotic genes as early biomarkers in the detection of tubular kidney damage. Further, cisplatin was shown to have a greater nephrotoxic effect than gentamicin; therefore, its use should be constrained accordingly when co-administered with gentamicin.

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Saccharomyces boulardii alleviates ulcerative colitis carcinogenesis in mice by reducing TNF-α and IL-6 levels and functions and by rebalancing intestinal microbiota

BMC Microbiology ◽

10.1186/s12866-019-1610-8 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 12

Author(s):

Chunsaier Wang ◽

Wenbin Li ◽

Hongying Wang ◽

Yiming Ma ◽

Xinhua Zhao ◽

...

Keyword(s):

Ulcerative Colitis ◽

Treatment Group ◽

Intestinal Microbiota ◽

Treated Group ◽

Saccharomyces Boulardii ◽

Inhibition Mechanism ◽

Control Group ◽

Rdna Sequencing ◽

Tnf Α ◽

Tumor Load

Abstract Background and Aims To explore the inhibition mechanism of Saccharomyces boulardii (S. boulardii) on ulcerative colitis (UC) carcinogenesis. Methods C57BL/6 mice were treated with azoxymethane and dextran sulfate sodium (AOM/DSS) to develop a UC carcinogenesis model. The treatment group was lavaged with S. boulardii (5 × 107 CFU/d) for 12 weeks. The mice were sacrificed and the tumor load in the treatment group was compared with that of a control group. The levels of TNF-α and IL-6 in colon tissue were measured by enzyme-linked immunosorbent assays. The influence of S. boulardii on TNF-α and IL-6 regulation was also investigated using different colon cell lines. Differences in intestinal microbiota in both stool and intestinal mucosa samples were assessed using 16S rDNA sequencing. Results S. boulardii treatment reduced AOM/DSS-induced UC carcinogenesis in mice, as indicated by the reduced tumor load and reduced TNF-α and IL-6 levels in vivo, as well its effects on TNF-α and IL-6 activities in vitro. Significant changes in both fecal and mucosal microbiota were observed among the control, the AOM/DSS treated, and AOM/DSS plus S. boulardii treated groups. For fecal microbiota, the AOM/DSS treated group was lower in Lactobacillus, but higher in Oscillibacter and Lachnoclostridium than the control group. After intervention with S. boulardii, the percentage of Bacillus and Lactococcus increased, but Lachnoclostridium, Oscillibacter, Bacteroides, and Pseudomonas decreased. For the intestinal mucosal microbiota, the AOM/DSS treated group was lower in Bifidobacterium and Ruminococcaceae_UCG-014 and higher in Alloprevotella than the control group. After S. boulardii exposure, the percentage contributions of Lachnoclostridium and Lachnospiraceae_NK4A136 increased. Conclusions S. boulardii effectively reduced UC carcinogenesis in an AOM/DSS induced mice model. This positive result can likely be attributed to the reduction of TNF-α and IL-6 levels or the blockade of their function combined with alterations to the intestinal microbiota.

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Immunomodulatory Activity of the Marine Sponge, Haliclona (Soestella) sp. (Haplosclerida: Chalinidae), from Sri Lanka in Wistar Albino Rats: Immunosuppression and Th1-Skewed Cytokine Response

Journal of Immunology Research ◽

10.1155/2020/7281295 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Varuni Gunathilake ◽

Marco Bertolino ◽

Giorgio Bavestrello ◽

Preethi Udagama

Keyword(s):

Bone Marrow ◽

Sri Lanka ◽

Marine Sponge ◽

Ex Vivo ◽

Rat Plasma ◽

Cytokine Response ◽

Albino Rats ◽

Immunomodulatory Activity ◽

Cell Counts ◽

Tnf Α

Natural secondary metabolites of sponges of the genus Haliclona are associated with an array of biological activity with therapeutic usage. We investigated the immunopharmacological properties of a presumably novel marine sponge species from Sri Lanka, Haliclona (Soestella) sp. Sponge material was collected from southern Sri Lanka by scuba diving. Sponge identification was based on spicule and skeleton morphology using light microscopy. Selected in vivo and ex vivo tests investigated nonfunctional and functional immunomodulatory activity of the Haliclona (Soestella) sp. crude extract (HSCE) in the Wistar rat model. Compared to the controls, rats orally gavaged daily for 14 consecutive days with 15 mg/kg dose of the HSCE manifested a significant reduction of immune cell counts of total WBCs (by 17%; p < 0.01 ), lymphocytes (38%), platelets (52%), splenocytes (20%), and bone marrow cells (BMC; 60%) ( p < 0.001 ), with a concurrent increase in the neutrophil : lymphocyte ratio ( p < 0.05 ); RBC counts abated by 53% ( p < 0.001 ). A significant reduction of the splenosomatic index was evident with the 10 and 15 mg/kg doses ( p < 0.001 ). Rat plasma TNF-α cytokine level was augmented by tenfold ( p < 0.001 ), IL-6 level by twofold ( p < 0.01 ) with the 15 mg/kg HSCE treatment, while IL-10 was detectable in rat plasma only with this treatment; the corresponding Th1 : Th2 cytokine ratio (TNF-α : IL-10) was indicative of an unequivocal Th1-skewed cytokine response ( p < 0.01 ). Ex vivo bone marrow cell and splenocyte proliferation were significantly and dose dependently impaired by HSCE ( I C 50 0.719 and 0.931 μg/mL, respectively; p < 0.05 ). Subacute toxicity testing established that HSCE was devoid of general toxic, hepatotoxic, and nephrotoxic effects. In conclusion, HSCE was orally active, nontoxic, and effectively suppressed nonfunctional and functional immunological parameters of Wistar rats, suggestive of the potential use of the HSCE as an immunosuppressant drug lead.

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Anti-diabetic Efficacy of Silver Nanoparticles Biosynthe-sized from Marine Red Seaweed Halymenia porphyroides Boergesen on Alloxan Stimulated Hyperglycemic Activity in Rats

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2021.14.5.8 ◽

2021 ◽

Vol 14 (5) ◽

pp. 5639-5646

Author(s):

Vishnu Kiran Manam ◽

Subbaiah Murugesan

Keyword(s):

Silver Nanoparticles ◽

Body Weight ◽

Treatment Group ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Treated Group ◽

The Body ◽

Albino Rats ◽

Red Seaweed

The assessment of silver nanoparticles biosynthesized and characterized using UV-Spec, FTIR, XRD, TGA, SEM, TEM from marine red seaweed Halymenia porphyroides have been evaluated for its anti-hyperglycemic activity in vivo. The anti-diabetic efficacy of the biosynthesized silver nanoparticles from marine red seaweed Halymenia porphyroides was studied by chemically inducing diabetes in the experimental Wistar albino rats through Alloxan monohydrate, which ultimately results in hyperglycemia at a dosage of 50 mg/kg body weight given orally for about 28 days. The outcome of the results was estimated by various biochemical parameters from the treatment group with silver nanoparticle (50 mg/Kg i.p) biosynthesized from Halymenia porphyroides. The anti-diabetic efficacy of the treatment group showed a decrease in the levels of blood glucose levels, total cholesterol, triglycerides, low-density lipoprotein, and phospholipids whereas the body weight and HDL increase was observed. The histopathological evaluation of the pancreas of the treated group of animals revealed the restoration and regeneration of β-cells of the pancreas with moderate swelling as compared to that of the chemically induced alloxan diabetic group of animals.

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Concomitant using of topical carrageenan-kappa and oral vitamin D against 7, 12-dimethylbenz[a]anthracene induced-oral cancer in rats: A synergism or an antagonism effects

Brazilian Dental Science ◽

10.14295/bds.2020.v23i3.1926 ◽

2020 ◽

Vol 23 (3) ◽

Author(s):

Aseel J Ali ◽

Jamal N.A. Al-Juboori ◽

Marwan Al-Nimer

Keyword(s):

Vitamin D ◽

Oral Cancer ◽

Treated Group ◽

Group Iv ◽

Antiproliferative Effect ◽

Lower Percentage ◽

Control Group ◽

Albino Rats ◽

Group I ◽

Tnf Α

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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