SULFASALAZINE ATTENUATES ULCERATIVE COLITIS IN RATS VIA DOWNREGULATION OF MIRNA-31, METALLOPROTEINASE-3 AND HIGH MOBILITY GROUP BOX1

Objective: This study targets the inhibition of inflammatory mediators and the enhancement of gastrointestinal mucosa healing in ulcerative colitis in rats through sulfasalazine. Methods: Twenty four female albino rats were divided into 3 groups: normal control, colitis group (rats received 5% dextran sodium sulfate (DSS) in their drinking water for 7 d), sulfasalazine group (500 mg/kg/day was administrated orally one week ahead of DSS and parallel with its administration). The impact of sulfasalazine on intestinal inflammation was investigated via estimation of some inflammatory mediators, namely; serum Leucine rich α 2 Glycoprotein (LRG) as well as colon cAMP, Myloperoxidase (MPO) and TNF-α using ELISA technique as well as gene expression of Trefoil Factor 3 (TFF3), High mobility group box1 (HMGB1), Nuclear factor kappa B (NF-κB) and metalloproteinase-3 (MMP3) and miRNA-31 levels using RT-PCR. Results: Sulfasalazine substantially decreases the release of LRG, MPO and TNF-α and the expression of HMGB1, NF-κB, MMP3, TFF3 and miRNA31 at p≤ 0.05 compared to colitis group in vivo. Moreover, Sulfasalazine significantly increases the colonic cAMP at p≤ 0.05 in groups of rats treated with DSS. Conclusion: Sulfasalazine has a protective effect on inflammatory bowel disease causing mucosal healing within the gastrointestinal tract. Additional studies are warranted to explore the molecular mechanism of sulfasalazine in ulcerative colitis and its clinical application

Antitumor and structure antioxidant activity relationship of Colchicine on Ehrlich ascites Carcinoma (EAC) in Female Mice

Colchicine has been reported to play important roles in hepatoprotection, anti-inflammation in vitro anti cancer activity. The present study was initiated to evaluate antioxidant and anti-cancer effects of colchicine (10µg/mice, i.p.) in mice after subcutaneous implantation of ehrlich ascites carcinoma (EAC) for 21 days. On the 22th day, the mice were sacrificed for the estimation of tumor growth, and biochemical parameters (glucose, insulin, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), lipid peroxides (TBARS), protein thiols (Pr-SHs), reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), total cholesterol (TC), triglycerides (TG), HDL-C, LDL-C, 17β-estradiol and progesterone). The results of this study showed that administration of colchicine and 5-Flourouracil individually for 21 days to the carcinoma induced mice demonstrated a significant (P<0.01) decrease in tumor weight and a significant (P<0.01) improvement in biochemical parameters and life span  compared to the EAC control mice. In addition, the results clearly suggest that colchicine induced antioxidant activity on experimental EAC control mice

The Protective Effects of Curcuminand Caffeic acid alone or in combination onNicotine-induced Lung Injury in Rats

The present study was performed to explore the protective effects ofcaffeic acid (20 mg/kg.bw) and curcumin (50mg/k.g.b.w.) on nicotine-induced lung injury alone and in combination.Their effect was compared to N-acetylcysteine (500mg/k.g.b.w.)  as known modulator of oxidative stress.  Nicotine treatment (0.6mg/kg/day, i.p, for 21 consecutivedays) resulted in a significantincrease (p<0.05) in plasmaalanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C) and well as plasma and lung thiobarbituric acid reactive substances (TBARS), nitric oxide(NO) and tumor necroses factor-α (TNF-α) concomitant with significant decline in non-enzymatic antioxidant like reduced glutathione(GSH) and in enzymatic antioxidants like catalase (CAT) andsuperoxide dismutase (SOD) as well as high density lipoprotein cholesterol (HDL-C). Furthermore, nicotine treatment caused severe injury indicated bythe histopathological examination of lung tissue compared to normal control group. Oral treatment with caffeic acid alone orcurcuminalone or in combination as well as N-acetylcysteine alone prevented the elevation in plasma ALT, AST, LDH,TC, TG, LDL-C, NO, TNF-α and TBARSlevels concomitant with an increments in the HDL-C, reduced glutathione GSH and antioxidant enzymes (CAT and SOD) and amelioration inhistopathological changes and injury induced by nicotine. Lung protection was prominent in curcuminand N-acetylcysteine alone more than caffeic acid alone or caffeic acid and curcuminin combination. Moreover, curcumin has the potential to be used in a combination therapy with caffeic acid, with decreasing the therapeutic dose of caffeic acid and therefore its side-effects.

The Protective Effects of Curcuminand Caffeic acid alone or in combination onNicotine-induced Lung Injury in Rats

The present study was performed to explore the protective effects ofcaffeic acid (20 mg/kg.bw) and curcumin (50mg/k.g.b.w.) on nicotine-induced lung injury alone and in combination.Their effect was compared to N-acetylcysteine (500mg/k.g.b.w.)  as known modulator of oxidative stress.  Nicotine treatment (0.6mg/kg/day, i.p, for 21 consecutivedays) resulted in a significantincrease (p<0.05) in plasmaalanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C) and well as plasma and lung thiobarbituric acid reactive substances (TBARS), nitric oxide(NO) and tumor necroses factor-α (TNF-α) concomitant with significant decline in non-enzymatic antioxidant like reduced glutathione(GSH) and in enzymatic antioxidants like catalase (CAT) andsuperoxide dismutase (SOD) as well as high density lipoprotein cholesterol (HDL-C). Furthermore, nicotine treatment caused severe injury indicated bythe histopathological examination of lung tissue compared to normal control group. Oral treatment with caffeic acid alone orcurcuminalone or in combination as well as N-acetylcysteine alone prevented the elevation in plasma ALT, AST, LDH,TC, TG, LDL-C, NO, TNF-α and TBARSlevels concomitant with an increments in the HDL-C, reduced glutathione GSH and antioxidant enzymes (CAT and SOD) and amelioration inhistopathological changes and injury induced by nicotine. Lung protection was prominent in curcuminand N-acetylcysteine alone more than caffeic acid alone or caffeic acid and curcuminin combination. Moreover, curcumin has the potential to be used in a combination therapy with caffeic acid, with decreasing the therapeutic dose of caffeic acid and therefore its side-effects.

Cranberry Extract as a Supplemented Food in Treatment of Oxidative Stress and Breast Cancer Induced by N-methyl-N-nitrosourea in Female Virgin Rats

Breast cancer is the most common cancer and a major cause of death in women. The present study was designed to evaluate the antioxidant and anticancer potential of cranberry extract against N-methyl-N-nitrosourea (MNU) induced mammary carcinoma in rats. The tumor was induced in Female virgin rats of age 50 days by single dose of MNU (50mg/kg.b.w i.p.). After 85 days; all rats developed at least one tumor. Animals were treated with cranberry extract (400 and 600 mg/kg.b.w.orally) and tamoxifen (2mg/kg.b.w.  i.p) for 4 weeks (from day 86 to day 113). MNU treatment resulted in a significant decrease (p < 0.05) in blood hemoglobin (Hb), red blood cells (RBC), platelets (PLTs) as well as blood, liver and breast catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD). However, MNU treatment resulted in a significant increase in White blood cells (WBC) as well as plasma, liver and mammary tissue gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH), hexosamine, sialic acid and thiobarbituric acid reactive substances (TBARs). Upon administration of the cranberry extract, the levels of WBC, GGT, LDH, hexosamine, sialic acid, TBARs, Hb, RBC, PLTs, CAT, GPx and SOD were significantly normalized. Histopathological changes also confirmed the formation of tumor tubules and neovascularization after the MNU treatment. Cranberry extract administration significantly reduces the growth of MNU-induced mammary tumors, and therefore has strong potential as a useful therapeutic regimen for inhibiting breast cancer development. Comparing the beneficial effect of cranberry extract with that of MNU-induced breast cancer, cranberry extract showed antitumor and antioxidant activity indicated by the measured biochemical parameters and the histopathological examination of mammary tissue. The results of the present study indicate that cranberry extract possesses strong anticancer effects through its role in modulating glycoprotein components and the levels of oxidative stress biomarkers. Cranberry exerted a stronger anticancer effect at the dosage of 600 mg/kg body weight than at dosage 400 mg/kg body weight.

Hepatoprotective effect of ginger and grape seed, alone and in combination orally, in paracetamol induced acute liver toxicity in rats

274-281Liver toxicity due to overdoses of common medicines is not uncommon. Paracetomol (acetaminophen) is one of the most common medicines prescribed by physicians and its overdose is toxic to liver. Here, we investigated the hepatoprotective effects of ginger and grape seed alone and/or in combination against paracetamol induced liver toxicity in rats as the ginger may potentiate the effect of grape seed. Fifty-Six male albino rats were divided into seven groups: group (I) normal control, (II) positive control, (III & V) rats treated with ginger extract, (IV & VI) rats treated with grape seed extract and (VII) rats treated with ginger extract and grape seed extract in combination. All extracts were administered orally for 28 days. On day 29, groups II, V, VI and VII were orally administrated a single dose of paracetamol (2 g/kg) which resulted into a significant increase in plasma liver enzymes, TNF-α, NO and TBARS, and also a significant decrease in liver antioxidants as well as plasma HDL. Our results showed that the ginger and grape seed alone may be effective in the protection of liver toxicity. However, prominent effect was found in the combined treatment through radical scavenging effect and antioxidant activity which is confirmed by histopathological examination of the liver

Cranberry Extract as a Supplemented Food in Treatment of Oxidative Stress and Breast Cancer Induced by N-methyl-N-nitrosourea in Female Virgin Rats

Breast cancer is the most common cancer and a major cause of death in women. The present study was designed to evaluate the antioxidant and anticancer potential of cranberry extract against N-methyl-N-nitrosourea (MNU) induced mammary carcinoma in rats. The tumor was induced in Female virgin rats of age 50 days by single dose of MNU (50mg/kg.b.w i.p.). After 85 days; all rats developed at least one tumor. Animals were treated with cranberry extract (400 and 600 mg/kg.b.w.orally) and tamoxifen (2mg/kg.b.w.  i.p) for 4 weeks (from day 86 to day 113). MNU treatment resulted in a significant decrease (p < 0.05) in blood hemoglobin (Hb), red blood cells (RBC), platelets (PLTs) as well as blood, liver and breast catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD). However, MNU treatment resulted in a significant increase in White blood cells (WBC) as well as plasma, liver and mammary tissue gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH), hexosamine, sialic acid and thiobarbituric acid reactive substances (TBARs). Upon administration of the cranberry extract, the levels of WBC, GGT, LDH, hexosamine, sialic acid, TBARs, Hb, RBC, PLTs, CAT, GPx and SOD were significantly normalized. Histopathological changes also confirmed the formation of tumor tubules and neovascularization after the MNU treatment. Cranberry extract administration significantly reduces the growth of MNU-induced mammary tumors, and therefore has strong potential as a useful therapeutic regimen for inhibiting breast cancer development. Comparing the beneficial effect of cranberry extract with that of MNU-induced breast cancer, cranberry extract showed antitumor and antioxidant activity indicated by the measured biochemical parameters and the histopathological examination of mammary tissue. The results of the present study indicate that cranberry extract possesses strong anticancer effects through its role in modulating glycoprotein components and the levels of oxidative stress biomarkers. Cranberry exerted a stronger anticancer effect at the dosage of 600 mg/kg body weight than at dosage 400 mg/kg body weight.

Hepatoprotective effect of ginger and grape seed, alone and in combination orally, in paracetamol induced acute liver toxicity in rats

274-281Liver toxicity due to overdoses of common medicines is not uncommon. Paracetomol (acetaminophen) is one of the most common medicines prescribed by physicians and its overdose is toxic to liver. Here, we investigated the hepatoprotective effects of ginger and grape seed alone and/or in combination against paracetamol induced liver toxicity in rats as the ginger may potentiate the effect of grape seed. Fifty-Six male albino rats were divided into seven groups: group (I) normal control, (II) positive control, (III & V) rats treated with ginger extract, (IV & VI) rats treated with grape seed extract and (VII) rats treated with ginger extract and grape seed extract in combination. All extracts were administered orally for 28 days. On day 29, groups II, V, VI and VII were orally administrated a single dose of paracetamol (2 g/kg) which resulted into a significant increase in plasma liver enzymes, TNF-α, NO and TBARS, and also a significant decrease in liver antioxidants as well as plasma HDL. Our results showed that the ginger and grape seed alone may be effective in the protection of liver toxicity. However, prominent effect was found in the combined treatment through radical scavenging effect and antioxidant activity which is confirmed by histopathological examination of the liver

Tentatively Identified (UPLC/T-TOF–MS/MS) Compounds in the Extract of Saussurea costus Roots Exhibit In Vivo Hepatoprotection via Modulation of HNF-1α, Sirtuin-1, C/ebpα, miRNA-34a and miRNA-223

Saussurea costus is a plant traditionally used for the treatment of several ailments. Our study accomplished the UPLC/T-TOF–MS/MS analysis of a methanol extract of Saussurea costus roots (MESC), in addition to lipoidal matter determination and assessment of its in vivo hepatoprotective activity. In this study, we were able to identify the major metabolites in MESC rather than the previously known isolated compounds, improving our knowledge of its chemical constituents. The flavones apigenin, acacetin, baicalein, luteolin, and diosmetin, and the flavonol aglycones quercetin, kaempferol, isorhamnetin, gossypetin, and myricetin and/or their glycosides and glucuronic derivatives were the major identified compounds. The hepatoprotective activity of MESC was evaluated by measuring catalase activity using UV spectrophotometry, inflammatory cytokines and apoptotic markers using ELISA techniques, and genetic markers using PCR. Paracetamol toxicity caused a significant increase in plasma caspase 2, cytokeratin 18 (CK18), liver tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), miRNA-34a, and miRNA-223, as well as a significant decrease in liver catalase (CAT) activity and in the levels of liver nuclear factor 1α (HNF-1α), sirtuin-1, and C/ebpα. Oral pretreatment with MESC (200 mg/kg) showed a significant decrease in caspase 2, CK18, TNF-α, IL-6 and a significant increase in liver CAT activity. MESC decreased the levels of liver miRNA-34a and miRNA-223 and induced HNF-1α, sirtuin-1, and C/ebpα gene expression. The histological examination showed a significant normalization in rats pretreated with MESC. Our findings showed that Saussurea costus may exert a potent hepatoprotective activity through the modulation of the expression of cellular cytokines, miRNA-34a, and miRNA-223