Renata Minuzzo Hartmann

Effect of Boswellia serrata on Antioxidant Status in an Experimental Model of Colitis Rats Induced by Acetic Acid

Aim of the StudyTo evaluate the antioxidant effect of an extract of the plant Boswellia serrata in an experimental model of acute ulcerative colitis induced by administration of acetic acid (AA) in rats.Materials and MethodsThe extract of B. serrata (34.2xa0mg/kg/day) was administered orally by gavage for 2xa0days before and after induction of colitis with AA diluted to 4xa0% and in a volume of 4xa0ml.ResultsThe anal sphincter pressure in the groups treated with B. serrata showed a significant increase compared to the colitis group (Pxa0<xa00.001). Histological analysis of treated animals showed less edema with preservation of mucosal crypts. Lipid peroxidation showed a significant decrease in the treated groups compared to the colitis group (Pxa0<xa00.001). The superoxide dismutase (SOD) enzyme activity showed a significant reduction in the treated groups compared to the colitis group (Pxa0<xa00.001), the glutathione peroxidase (GPx) significantly increased in the treated groups compared to colitis group (Pxa0<xa00.05), and the same was the result for enzyme activity glutathione (GSH; Pxa0<xa00.05).ConclusionsThe extract of B. serrata has active antioxidant substances that exert protective effects in acute experimental colitis.

Boswellia serrata has Beneficial Anti-Inflammatory and Antioxidant Properties in a Model of Experimental Colitis

Ulcerative colitis is an inflammatory disease that involves only the colon and rectum, being characterized by leukocyte infiltrate and superficial ulcers in the intestinal mucosa. To evaluate the anti‐inflammatory and antioxidant effects of extract from the Boswellia serrata plant in an experimental rat model of acute ulcerative colitis induced by the administration of acetic acid (AA). An extract of B. serrata (34.2u2009mg/kg/day) was administered by oral gavage for 2u2009days before and after the induction of colitis with 4u2009mL of 4% AA. The anal sphincter pressure in the colitis group showed a significant decrease compared to that of the control groups (pu2009<u20090.001). The analysis of the values of lipid peroxidation (LPO) obtained by substances that react with thiobarbituric acid (TBARS) showed a significantly increased LPO in the colitis group compared to the control groups (pu2009<u20090.001). The nitric oxide levels and the expression of inducible nitric oxide synthase (iNOS) showed a significant increase in the colitis group compared to control groups (pu2009<u20090.01). Both pretreatment and treatment with B. serrata exhibited significantly reduced lipid peroxidation, nitric oxide and iNOS and showed improvements in tissue injury and anal sphincter pressure in animals with ulcerative colitis. The B. serrata extract has protective anti‐inflammatory and antioxidant effects that inhibit inflammatory mediators in acute experimental colitis. Copyright

ACTION OF VITAMIN E ON EXPERIMENTAL SEVERE ACUTE LIVER FAILURE

CONTEXTO A Insuficiencia Hepatica Aguda Grave (IHAG) e uma sindrome clinica potencialmente fatal, na qual ocorre necrose dos hepatocitos, perda da arquitetura hepatica e deterioracao de suas funcoes. Dentre as principais causas da IHAG esta a hepatotoxicidade decorrente de agentes quimicos, que lesam os hepatocitos e acarretam aumento das especies reativas de oxigenio. A vitamina E tem alta atividade antioxidante biologica e e amplamente distribuida nos tecidos. OBJETIVO Avaliar o efeito antioxidante da Vitamina E no modelo de IHAG. METODOS Foram utilizados 56 ratos, com peso medio de 300 g, divididos em oito grupos, quatro grupos avaliados em 24 horas e quatro em 48 horas apos a inducao: grupo controle (CO); Vitamina E (Vit.E); Tioacetamida (TAA) e Tioacetamida + Vitamina E (TAA+Vit.E). Os ratos foram submetidos a injecoes de tioacetamida, na dose de 400 mg/Kg de peso i.p., no inicio do experimento e, posteriormente, apos 8 horas. A vit E (100 mg//Kg i.p.) foi administrada 30 minutos apos a segunda dose de tioacetamida. Os animais do tempo 48 horas receberam mais duas doses de vit. E (24h e 36h). Transcorridas 24 ou 48 horas apos a administracao da primeira dose de TAA, os animais foram pesados, anestesiados e o sangue retirado para a avaliacao da integridade hepatica atraves das enzimas Aspartatoaminotransferase (AST) e Alanina aminotransferase (ALT). O tecido hepatico foi retirado para avaliacao da lipoperoxidacao atraves da tecnica de TBARS, atividade das enzimas antioxidantes SOD, CAT, GPx, e GST, avaliacao de NO 2 /NO 3 e avaliacao histologica pela coloracao de hematoxilina e eosina nos dois tempos. Os resultados foram expressos como media ± erro padrao e a analise estatistica utilizada foi ANOVA, seguido de teste de Student-Newman-Keuls, considerado significativo P <0,05. RESULTADOS Apos o tratamento com a vit. E, observamos uma reducao nas enzimas de integridade hepatica AST (U/L) (101,32±19,45 em 24h e 97,85±29,65 em 48h) relacionado ao grupo TAA (469,56±20,69 em 24h e 598,23±55,45 em 48h) e ALT (U/L) (76,59±8,56 em 24h e 68,47±6,49 em 48h) comparado ao grupo TAA (312,21±10,23 em 24h e 359,15±17,58 em 48h). Houve uma reducao da LPO (nmol/mg Prot), no grupo TAA+Vit.E (0,77±0,07 em 24h e 0,95±0,08 em 48h) comparado ao grupo TAA (1,50±0,07 em 24h e 1,65±0,16 em 48h). A SOD (USOD/min/mg Prot) diminuiu no grupo TAA+Vit.E (49,48±9,47 em 24h e 62,45±18,47 em 48h) relacionado ao grupo TAA (98,46±15,48 em 24h e 154,13±21,46 em 48h), assim como a GST (nmol/min/mg Prot) no grupo TAA+Vit.E (350,57±36,93 em 24h e 453,29±13,84 em 48h) comparado ao grupo TAA (561,57±64,56 em 24h e 673,43±38,13 em 48h). Houve aumento da CAT (pmol/min/mg Prot) no grupo TAA+Vit.E (3,40±0,44 em 24h e 3,01±0,35 em 48h) em relacao ao grupo TAA (1,65±0,21 em 24h e 1,86±0,42 em 48h). A GPx (nmol/min/mg Prot) aumentou em 24h no grupo TAA+Vit.E (1,01±0,16) comparado ao grupo TAA (0,41±0,04) e diminuiu em 48h (1,19±0,17) em relacao ao grupo TAA (1,76±0,21). Verificou-se reducao nos niveis de NO 2 /NO 3 (mmol/L) no grupo TAA+Vit.E (31,47±4,26 em 24h e 38,93±5,20 em 48h) em relacao ao grupo TAA (49,37±5,12 em 24h e 53,53±5,97 em 48h). A avaliacao histopatologica mostrou diminuicao da lesao hepatica (necrose e inflamacao) em ambas os tempos estudados. CONCLUSAO Estes resultados sugerem que a vitamina E foi capaz de proteger o figado de lesoes causadas por tioacetamida.

Effect of glutamine on liver injuries induced by intestinal ischemia-reperfusion in rats

INTRODUCTIONnIntestinal ischemia-reperfusion (I/R) injury may cause cell and tissue damage, reaching also other organs such as the liver. Because of the involvement of free radicals in I/R injury, treatment options with antioxidants have been studied and tested.nnnOBJECTIVEnTo evaluate the effect of glutamine (Gln) in the liver of animals with intestinal I/R injury.nnnMETHODSnWe used 20 male Wistar rats divided into four groups: sham-operated (SO); glutamine + sham-operated (G+SO); intestinal ischemia-reperfusion (I/R); glutamine + intestinal ischemia-reperfusion (G+I/R). The superior mesenteric artery was clamped for 30 minutes and reperfused for 15 minutes. Gln (25 mg/kg/day) diluted in 1 ml of saline was administered intraperitoneally on the two days before I/R induction.nnnRESULTSnLevels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), lipid peroxidation (LPO) and expressions of interleukin-6 (IL-6) and nuclear factor kappa B (NF-kB) showed a significant reduction in the G+I/R group as compared with the I/R group. The activity of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and the levels of glutathione (GSH) showed an increase in the G+I/R group as compared with the I/R group.nnnCONCLUSIONnPretreatment with Gln reduced oxidative, tissue damage and showed a decrease expression of inflammatory mediators.

Protective effect of glutamine on the main and adjacent organs damaged by ischemia-reperfusion in rats

Intestinal ischemia and reperfusion (I/R) causes cellular and tissue damage to the intestine and remote organs such as the liver. Increased production of ROS and nitric oxide and dysregulation of cytoprotective enzymes may be involved in intestinal I/R. The aim was to evaluate the protective effects of glutamine on the intestine and liver of rats with intestinal I/R injury. Twenty male Wistar rats (300xa0g) were divided into four groups: sham-operated (SO), glutamine + SO (Gxa0+xa0SO), I/R, and glutamine + I/R (Gxa0+xa0I/R). Occlusion of the SMA for 30xa0min was followed by 15-min reperfusion. Glutamine (25xa0mg/kg/day) was administered once daily 24 and 48xa0h before I/R induction. Blood and tissue of were collected for aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, histopathological analysis, immunohistochemistry of IL-1β and TNF-α, thiobarbituric acid reactive substance (TBARS) and nitric oxide, Nrf2/keap1, superoxide dismutase (SOD), NADPH quinone oxidoreductase1 (NQO1), inducible nitric oxide synthase (iNOS), heat shock protein (HSP70), glucose-regulated protein 78 (GRP78), and activating transcription factor 6 (ATF-6) by western blot. Statistic analysis by ANOVA–Student-Newman-Keuls test (meanxa0±xa0SE) significantly was pxa0<xa00.05. Tissue damage, AST, ALT, IL-1β, TNF-α, TBARS, NO, Keap1, iNOS, GRP78, and ATF-6 expression were significantly lower in the Gxa0+xa0I/R group as compared to the I/R group. Expression of Nrf2, SOD, NQO1, and HSP70, was significantly higher in the Gxa0+xa0I/R group as compared to I/R group. Pre-treatment with glutamine provided protection against oxidative damage in the intestine and liver in an experimental model of intestinal I/R.

P0091 : N-acetylcysteine modulates angiogenesis, vasodilation and dna damage in stomach of portal hypertensive rats

secretion to overcome the IR. Recently, Douglas A. Melton’s group from Harvard University reported the identification of betatrophin as a circulating protein secreted from the liver under insulin resistant states which is sufficient to dramatically and specifically increase the replication of B-cells in mouse resulting in an increased functional B-cell mass over time. In addition, in human studies betatrophin levels are associated with indexes of IR. The role of betatrophin in cirrhosis is at present unknown. The aim of this study was to investigate plasma levels of betatrophin in cirrhosis Methods: We measured plasma betatrophin concentrations in 40 patients with cirrhosis (27 in Child–Pugh’s class B, and 13 in Child– Pugh’s class C) and compared these values with those in 15 agematched healthy subjects. According to MELD score, 20 patients showed a MELD score higher than 14. IR was assessed by the Homeostasis Model Assessment (HOMA). Results: Plasma betatrophin levels were significantly increased in patients with cirrhosis compared with healthy subjects. In addition, we found a positive correlation between plasma betatrophin levels and severity of cirrhosis according Child–Pugh or MELD score. Moreover, IR in cirrhotic patients was seen in 82.5%. In these group of patients betatrophin levels were significantly higher than group of patients without IR. Conclusions: Plasma betatrophin is increased in patients with cirrhosis compared with healthy subjects. The increase in plasma betatrophin levels is related to the severity of cirrhosis as well as with the emergence of IR. Thus, these preliminary results show that betatrophin may contribute to counteract at least in part IR in patients with cirrhosis but more studies are needed to confirm it.