Exposure in the tobacco fields: Genetic damage and oxidative stress in tobacco farmers occupationally exposed during harvest and grading seasons.

Agricultural workers engaged in tobacco cultivation are constantly exposed to large amounts of harmful agents, such as pesticides and nicotine. Furthermore, most of the flue-cured tobacco leaves are manually graded exposing workers to agents such as tobacco-specific nitrosamines. This study aimed to evaluate genetic damage and oxidative stress in tobacco farmers occupationally exposed during the harvest and grading seasons. We obtained data on DNA damage detected in Comet assay in blood cells and micronucleus experiment with buccal cells from 241 individuals. The serum cotinine levels and nitrates were also evaluated. The Comet Assay results showed a showed an increased visual score for males and females during harvest time and tobacco grading. An increase of micronucleated and binucleated cells was observed in the grading group compared to the control and harvest groups. The oxidative stress measurements showed a clear increase of thiobarbituric acid reactive substances (TBARS) in tobacco farmers during harvest time, and trolox equivalent antioxidant capacity (TEAC) in individuals during harvest and grading time compared to the controls. Significant increases of the cotinine levels were observed during the harvest and grading period (harvest>grading), and nitrates for the grading period compared to the control. In this study, tobacco farmers presented compromised DNA integrity associated with enhanced oxidative stress levels.

Melatonin restores zinc levels, activates the Keap1/Nrf2 pathway, and modulates endoplasmic reticular stress and HSP in rats with chronic hepatotoxicity.

BACKGROUND: Melatonin (MLT) is a potent antioxidant molecule that is shown to have a beneficial effect in various pathological situations, due to its action against free radicals. AIM: To evaluate the effect of MLT on carbon tetrachloride (CCl4) induced liver injury in rats in terms of oxidative stress, reticular stress, and cell damage. METHODS: Twenty male Wistar rats (230-250 g) were divided into four groups: Control rats, rats treated with MLT alone, rats treated with CCl4 alone, and rats treated with CCl4 plus MLT. CCl4 was administered as follows: Ten doses every 5 d, ten every 4 d, and seven every 3 d. MLT was administered intraperitoneally at a dose of 20 mg/kg from the 10th wk to the end of the experiment (16th wk). RESULTS: MLT was able to reduce the release of liver enzymes in the bloodstream and to decrease oxidative stress in CCl4 treated rats by decreasing the level of thiobarbituric acid reactive substances and increasing superoxide dismutase activity, with a lower reduction in serum zinc levels, guaranteeing a reduction in liver damage; additionally, it increased the expression of nuclear factor (erythroid-derived 2)-like 2 and decreased the expression of Kelch-like ECH-associated protein 1. MLT also decreased the expression of the proteins associated with endoplasmic reticulum stress, i.e., glucose-regulated protein 78 and activating transcription factor 6, as well as of heat shock factor 1 and heat shock protein 70. CONCLUSION: MLT has a hepatoprotective effect in an experimental model of CCl4-induced liver injury, since it reduces oxidative stress, restores zinc levels, and modulates endoplasmic reticulum stress.

Exposure to organic solvents and hepatotoxicity.

The purpose of this study was to identify the long-term effect of chemical exposure on the liver. Laboratory tests included alanine aminotransferase (ALT) dosage and oxidative stress tests, such as thiobarbituric acid reactive substances in plasma and superoxide dismutase (SOD) and glutathione S-transferase analysis in erythrocytes. The cross-sectional study comprised 70 workers, 30 of them exposed to organic solvents and 40 not exposed. All those exposed presented at least 5 years of exposure to solvents. Hepatitis B and C, known hepatic disease, comorbidities, use of alcohol, illicit drugs or hepatotoxic medications, smoking, body mass index >30, female sex and age (<18 or >65) were excluded from the sample. Results indicated that elevated ALT was more frequent in the exposed group compared to controls: 33% vs. 10.5%, with a statistical significance (p < 0.05). Thiobarbituric acid reactive substances were significantly elevated (p < 0.01) in the exposed group in comparison to controls. Antioxidant enzymes were more elevated in the exposed group compared to controls: SOD 7.29 (4.30-8.91) USOD/mg of protein vs. 3.48 (2.98-5.28) USOD/mg of protein and GST 2.57 µmol/min/mg of protein (1.80-4.78) vs. 1.81 µmol/min/mg of protein (1.45- 2.30) µM/min/mg of protein. The results suggest an association between exposure to organic solvents and hepatotoxicity.

Simvastatin Reduces Hepatic Oxidative Stress and Endoplasmic Reticulum Stress in Nonalcoholic Steatohepatitis Experimental Model.

OBJECTIVE: In this study, we evaluated the efficacy of simvastatin in the treatment of nonalcoholic steatohepatitis induced by methionine and choline-deficient diet in mice and its possible effect on factors involved in the pathogenesis of the disease including oxidative stress and endoplasmic reticulum stress. METHOD: Male C57BL6 mice were fed either a normal diet (control) or a methionine and choline-deficient diet for four weeks and then treated orally with simvastatin (4 mg/kg once a day) for two final weeks. At the end of the experimental period, liver integrity, biochemical analysis, hepatic lipids, histology, DNA damage, biomarkers of oxidative stress, and endoplasmic reticulum stress were assessed. RESULTS: Simvastatin treatment was able to significantly reduce hepatic damage enzymes and hepatic lipids and lower the degree of hepatocellular ballooning, without showing genotoxic effects. Simvastatin caused significant decreases in lipid peroxidation, with some changes in antioxidant enzymes superoxide dismutase and glutathione peroxidase. Simvastatin activates antioxidant enzymes via Nrf2 and inhibits endoplasmic reticulum stress in the liver. CONCLUSIONS: In summary, the results provide evidence that in mice with experimental nonalcoholic steatohepatitis induced by a methionine and choline-deficient diet, the reduction of liver damage by simvastatin is associated with attenuated oxidative and endoplasmic reticulum stress.

Zinc supplementation reduces diet-induced obesity and improves insulin sensitivity in rats.

Rates of obesity have been growing at alarming rates, compromising the health of the world population. Thus, the search for interventions that address the metabolic repercussions of obesity are necessary. Here we evaluated the metabolic and antioxidant effects of zinc and branched-chain amino acids (BCAA) supplementation on obese rats. Male Wistar rats were fed either a high-fat/high-fructose diet (HFD) or a standard diet (SD) for 19 weeks. From the fifteenth week until the end of the experiment, HFD- and SD-fed rats received zinc (6 mg/kg) or BCAA (750 mg/kg) supplementation. Body weight, abdominal fat, lipid profile, blood glucose, insulin, leptin, and hepatic transaminases were evaluated. In the liver, superoxide dismutase and catalase activities and lipid peroxidation were also analyzed. HFD-fed animals showed increased weight gain, abdominal fat pad, plasma insulin, leptin, and triglycerides levels in comparison with SD-fed rats. Zinc supplementation reduced all these parameters, suggesting a beneficial role for the treatment of obesity. BCAA, on the other hand, did not show any beneficial effect. Liver antioxidant enzymes and hepatic transaminases plasma levels did not change among groups. Lipid peroxidation was higher in HFD-fed rats and was not reverted by zinc or BCAA supplementation. In conclusion, zinc supplementation may be a useful strategy for the treatment of the metabolic dysfunction associated with obesity.

Effects of remote ischemic preconditioning and topical hypothermia in renal ischemia-reperfusion injury in rats.

PURPOSE: To evaluate whether combining hypothermia and remote ischemic preconditioning (RIPC) results in protection from ischemia-reperfusion (IR). METHODS: Thirty-two Wistar rats underwent right nephrectomy and were randomly assigned to four experimental protocols on the left kidney: warm ischemia (group 1), cold ischemia (group 2), RIPC followed by warm ischemia (group 3), and RIPC followed by cold ischemia (group 4). After 240 minutes of reperfusion, histological changes in the left kidney, as well as lipid peroxidation and antioxidant enzyme activity, were analyzed. The right kidney was used as the control. Serum creatinine was collected before and after the procedures. RESULTS: RIPC combined with hypothermia during IR experiments revealed no differences on interventional groups regarding histological changes (p=0.722). Oxidative stress showed no significant variations among the groups. Lower serum creatinine at the end of the procedure was seen in animals exposed to hypothermia (p<0.001). CONCLUSIONS: Combination of RIPC and local hypothermia provides no renal protection in IR injury. Hypothermia preserves renal function during ischemic events. Furthermore, RIPC followed by warm IR did not show benefits compared to warm IR alone or controls in our experimental protocol.

Effects of remote ischemic preconditioning and topical hypothermia in renal ischemia-reperfusion injury in rats

Purpose:To evaluate whether combining hypothermia and remote ischemic preconditioning (RIPC) results in protection from ischemia-reperfusion (IR). Methods: Thirty-two Wistar rats underwent right nephrectomy and were randomly assigned to four experimental protocols on the left kidney: warm ischemia (group 1), cold ischemia (group 2), RIPC followed by warm ischemia (group 3), and RIPC followed by cold ischemia (group 4). After 240 minutes of reperfusion, histological changes in the left kidney, as well as lipid peroxidation and antioxidant enzyme activity, were analyzed. The right kidney was used as the control. Serum creatinine was collected before and after the procedures. Results: RIPC combined with hypothermia during IR experiments revealed no differences on interventional groups regarding histological changes (p=0.722). Oxidative stress showed no significant variations among the groups. Lower serum creatinine at the end of the procedure was seen in animals exposed to hypothermia (p 0.001). Conclusions: Combination of RIPC and local hypothermia provides no renal protection in IR injury. Hypothermia preserves renal function during ischemic events. Furthermore, RIPC followed by warm IR did not show benefits compared to warm IR alone or controls in our experimental protocol.(AU)

Effects of remote ischemic preconditioning and topical hypothermia in renal ischemia-reperfusion injury in rats

Abstract Purpose: To evaluate whether combining hypothermia and remote ischemic preconditioning (RIPC) results in protection from ischemia-reperfusion (IR). Methods: Thirty-two Wistar rats underwent right nephrectomy and were randomly assigned to four experimental protocols on the left kidney: warm ischemia (group 1), cold ischemia (group 2), RIPC followed by warm ischemia (group 3), and RIPC followed by cold ischemia (group 4). After 240 minutes of reperfusion, histological changes in the left kidney, as well as lipid peroxidation and antioxidant enzyme activity, were analyzed. The right kidney was used as the control. Serum creatinine was collected before and after the procedures. Results: RIPC combined with hypothermia during IR experiments revealed no differences on interventional groups regarding histological changes (p=0.722). Oxidative stress showed no significant variations among the groups. Lower serum creatinine at the end of the procedure was seen in animals exposed to hypothermia (p<0.001). Conclusions: Combination of RIPC and local hypothermia provides no renal protection in IR injury. Hypothermia preserves renal function during ischemic events. Furthermore, RIPC followed by warm IR did not show benefits compared to warm IR alone or controls in our experimental protocol.

Combined effects of melatonin and topical hypothermia on renal ischemia-reperfusion injury in rats.

PURPOSE: To evaluate whether their combination was more effective than either alone in decreasing renal damage due to ischemia/reperfusion (I/R) injury in rats. METHODS: Thirty-two Wistar rats were assigned to four groups. Following right nephrectomy, their left kidneys were subjected to warm ischemia (IR), cold ischemia (TH+IR), intraperitoneal injection of 10 mg/kg melatonin (MEL+IR), or injection of 10 mg/kg melatonin followed by cold ischemia (MEL+TH+IR). Eight randomly assigned right kidneys constituted the control group. After 240 min of reperfusion, left nephrectomy was performed for histopathological evaluation, lipid peroxidation, and measurement of antioxidant enzyme activity. Serum was collected to measure urea and creatinine concentrations. RESULTS: Histopathological damage induced by ischemia and reperfusion was more attenuated in the MEL+TH+IR group than in the MEL+IR and TH+IR groups (p<0.037). Superoxide dismutase activity was significantly higher (p<0.029) and creatinine (p<0.001) and urea (p<0.001) concentrations were significantly lower in the MEL+TH+IR group than in the MEL+IR and TH+IR groups. CONCLUSION: The combination of melatonin (MEL) and topical hypothermia (TH) better protects against renal I/R injury than does MEL or TH alone.

Combined effects of melatonin and topical hypothermia on renal ischemia-reperfusion injury in rats

Purpose: To evaluate whether their combination was more effective than either alone in decreasing renal damage due to ischemia/reperfusion (I/R) injury in rats. Methods: Thirty-two Wistar rats were assigned to four groups. Following right nephrectomy, their left kidneys were subjected to warm ischemia (IR), cold ischemia (TH+IR), intraperitoneal injection of 10 mg/kg melatonin (MEL+IR), or injection of 10 mg/kg melatonin followed by cold ischemia (MEL+TH+IR). Eight randomly assigned right kidneys constituted the control group. After 240 min of reperfusion, left nephrectomy was performed for histopathological evaluation, lipid peroxidation, and measurement of antioxidant enzyme activity. Serum was collected to measure urea and creatinine concentrations. Results: Histopathological damage induced by ischemia and reperfusion was more attenuated in the MEL+TH+IR group than in the MEL+IR and TH+IR groups (p<0.037). Superoxide dismutase activity was significantly higher (p<0.029) and creatinine (p<0.001) and urea (p<0.001) concentrations were significantly lower in the MEL+TH+IR group than in the MEL+IR and TH+IR groups. Conclusion: The combination of melatonin (MEL) and topical hypothermia (TH) better protects against renal I/R injury than does MEL or TH alone.(AU)

Combined effects of melatonin and topical hypothermia on renal ischemia-reperfusion injury in rats

Abstract Purpose: To evaluate whether their combination was more effective than either alone in decreasing renal damage due to ischemia/reperfusion (I/R) injury in rats. Methods: Thirty-two Wistar rats were assigned to four groups. Following right nephrectomy, their left kidneys were subjected to warm ischemia (IR), cold ischemia (TH+IR), intraperitoneal injection of 10 mg/kg melatonin (MEL+IR), or injection of 10 mg/kg melatonin followed by cold ischemia (MEL+TH+IR). Eight randomly assigned right kidneys constituted the control group. After 240 min of reperfusion, left nephrectomy was performed for histopathological evaluation, lipid peroxidation, and measurement of antioxidant enzyme activity. Serum was collected to measure urea and creatinine concentrations. Results: Histopathological damage induced by ischemia and reperfusion was more attenuated in the MEL+TH+IR group than in the MEL+IR and TH+IR groups (p<0.037). Superoxide dismutase activity was significantly higher (p<0.029) and creatinine (p<0.001) and urea (p<0.001) concentrations were significantly lower in the MEL+TH+IR group than in the MEL+IR and TH+IR groups. Conclusion: The combination of melatonin (MEL) and topical hypothermia (TH) better protects against renal I/R injury than does MEL or TH alone.

Protective effects of quercetin treatment in a pristane-induced mouse model of lupus nephritis.

INTRODUCTION: Lupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus. As murine models of LN are valuable tools to better understand its pathophysiology and to search for new effective treatments, we investigated the effects of the bioflavonoid quercetin on pristane-induced LN mice through histomorphological analyses. METHODS: Immunofluorescence and biochemical assays were used to evaluate the expression of markers of inflammation (interleukin-6, IL-6; tumour necrosis factor-α, TNF-α), oxidative stress (catalase, CAT; superoxide dismutase 1, SOD1; thiobarbituric acid reactive substances, TBARS), apoptosis (Bax), and fibrosis (transforming growth factor-ß1, TGF-ß1). Glomerular and tubular ultrastructure was analysed, and tissue messenger RNA of podocin, podoplanin and α3ß1-integrin were quantified using the real-time polymerase chain reaction. RESULTS: Pristane-induced LN mice showed severe kidney injury, characterized by increased proteinuria, glomerular mesangial expansion and inflammation, high expression of the pro-fibrotic, apoptotic and prooxidant markers and reduction of antioxidants. In the kidney ultrastructure, foot process (FP) effacement, apoptotic mesangial cells and abnormal mitochondria with disrupted cristae were observed, along with suppressed tissue mRNA of podocin, podoplanin and α3ß1-integrin. Treatment with quercetin in the pristane-induced LN mice model was nephroprotective, decreasing proteinuria levels and significantly lowering tissue expression of IL-6, TNF-α, TGF-ß1, Bax and TBARS. Simultaneously, quercetin significantly increased CAT and SOD1 expressions in these mice. In addition, it was observed improvement of the kidney ultrastructure, and tissue mRNA of podocin, but not podoplanin and α3ß1-integrin, was restored to the levels found in the control mice. CONCLUSION: In conclusion, these findings provide experimental evidence of the renoprotective effects of quercetin in the pristane-induced LN mice model. We suggest that quercetin effectively ameliorates the kidney damage caused by pristane, a bioflavonoid to be further evaluated as a new therapeutic strategy in this disease.

The effects of local ischemic preconditioning and topical hypothermia in renal ischemia/reperfusion injury in rats.

PURPOSE: Topical hypothermia and local ischemic preconditioning have been shown to reduce renal ischemia-reperfusion (I/R) injury individually. We examined whether combination of both strategies lessens renal I/R injury. METHODS: Post right nephrectomy, 40 male Wistar rats were randomly assigned to five experimental protocols performed in the left kidney: topical hypothermia without ischemia (TH), warm ischemia (IR), ischemic preconditioning followed by warm ischemia (IPC+IR), cold ischemia (TH+IR), and ischemic preconditioning followed by cold ischemia (IPC+TH+IR). Eight randomly assigned right kidneys constituted the control group. After 240 min of reperfusion, the left kidney was retrieved to evaluate histological changes, lipid peroxidation and antioxidant enzymes activity. Serum was collected to evaluate urea and creatinine. RESULTS: IPC+TH+IR group revealed no difference to any other group subjected to ischemia in relation to histological changes, lipid peroxidation and antioxidant enzymes activity. Creatinine was lower in IPC+TH+IR group compared with IPC+IR, but showed no difference compared to TH+IR group. CONCLUSIONS: Combination of local ischemic preconditioning (IPC) and topical hypothermia conferred no protection in renal I/R injury. Moreover, local IPC solely followed by warm ischemia impaired renal function more than warm ischemia alone.

The effects of local ischemic preconditioning and topical hypothermia in renal ischemia/reperfusion injury in rats

Purpose: Topical hypothermia and local ischemic preconditioning have been shown to reduce renal ischemia-reperfusion (I/R) injury individually. We examined whether combination of both strategies lessens renal I/R injury. Methods: Post right nephrectomy, 40 male Wistar rats were randomly assigned to five experimental protocols performed in the left kidney: topical hypothermia without ischemia (TH), warm ischemia (IR), ischemic preconditioning followed by warm ischemia (IPC+IR), cold ischemia (TH+IR), and ischemic preconditioning followed by cold ischemia (IPC+TH+IR). Eight randomly assigned right kidneys constituted the control group. After 240 min of reperfusion, the left kidney was retrieved to evaluate histological changes, lipid peroxidation and antioxidant enzymes activity. Serum was collected to evaluate urea and creatinine. Results: IPC+TH+IR group revealed no difference to any other group subjected to ischemia in relation to histological changes, lipid peroxidation and antioxidant enzymes activity. Creatinine was lower in IPC+TH+IR group compared with IPC+IR, but showed no difference compared to TH+IR group. Conclusions: Combination of local ischemic preconditioning (IPC) and topical hypothermia conferred no protection in renal I/R injury. Moreover, local IPC solely followed by warm ischemia impaired renal function more than warm ischemia alone.(AU)

The effects of local ischemic preconditioning and topical hypothermia in renal ischemia/reperfusion injury in rats

Abstract Purpose: Topical hypothermia and local ischemic preconditioning have been shown to reduce renal ischemia-reperfusion (I/R) injury individually. We examined whether combination of both strategies lessens renal I/R injury. Methods: Post right nephrectomy, 40 male Wistar rats were randomly assigned to five experimental protocols performed in the left kidney: topical hypothermia without ischemia (TH), warm ischemia (IR), ischemic preconditioning followed by warm ischemia (IPC+IR), cold ischemia (TH+IR), and ischemic preconditioning followed by cold ischemia (IPC+TH+IR). Eight randomly assigned right kidneys constituted the control group. After 240 min of reperfusion, the left kidney was retrieved to evaluate histological changes, lipid peroxidation and antioxidant enzymes activity. Serum was collected to evaluate urea and creatinine. Results: IPC+TH+IR group revealed no difference to any other group subjected to ischemia in relation to histological changes, lipid peroxidation and antioxidant enzymes activity. Creatinine was lower in IPC+TH+IR group compared with IPC+IR, but showed no difference compared to TH+IR group. Conclusions: Combination of local ischemic preconditioning (IPC) and topical hypothermia conferred no protection in renal I/R injury. Moreover, local IPC solely followed by warm ischemia impaired renal function more than warm ischemia alone.

Ductular reaction, cytokeratin 7 positivity, and gamma-glutamyl transferase in multistage hepatocarcinogenesis in rats.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and is characterized by multistage formation. The presence of ductular reaction, cytokeratin 7 positivity (PCK7), and increased levels of gamma glutamyltransferase (γGT) has been observed during liver carcinogenesis and contribute to tumor progression. Our goal was to evaluate the ductular reaction in multistage carcinogenesis and to correlate PCK7 and γGT levels with tumor incidence, histological characteristics, liver DNA damage index, and the expression of oxidative stress proteins. HCC was induced in 24 male Wistar rats weighing 145-150 g by chronic and intermittent exposure to 50 or 100 mg/kg diethylnitrosamine (DEN). Six control animals received only vehicle. Blood was collected to determine hepatic enzyme levels. Animals were divided into three groups: control (CO), precancerous lesions (PL), and advanced HCC. Liver samples were obtained for immunohistochemical analyses and the measurement of protein expression. Statistical analyses included Tukey's test and Pearson's correlation analyses. We observed an extensive ductular reaction in advanced HCC and a strong correlation between PCK7 and levels of γGT and the poor prognosis and aggressiveness of HCC. The extent of PCK7 and high γGT levels were associated with overexpression of inducible nitric oxide synthase (iNOS) and heat shock factor protein 1 (HSF-1). However, PCK7 and γGT levels were negatively correlated with protein expression of nuclear factor erythroid 2-related factor 2 (NRF2) and inducible heat shock protein 70 (iHSP70). These findings suggest that ductular reaction is involved in the progression of multistage hepatocarcinogenesis.

Alteration of taste buds in experimental cirrhosis. Is there correlation with human hypogeusia? / Alteração de paladar em um modelo experimental de cirrose. Existe correlação com hipogeusia humana?

ABSTRACT Background The inherent complications of cirrhosis include protein-calorie malnutrition and micronutrient deficiencies.Changes in taste are detrimental to the nutritional status, and the mechanism to explain these changes is not well documented in the cirrhotic patients. Objective To evaluate the taste buds of cirrhotic rats. Methods Fourteen male Wistar rats were evaluated. After 16 weeks, the liver was removed to histologically diagnose cirrhosis, and blood was collected to perform liver integrity tests. The tongue was removed for histological examination and immunohistochemistry using antibodies against protein gene product PGP 9.5 and the sweet taste receptors T1R2 and T1R3. Morphological changes were determined by scanning electron microscopy. Serum zinc levels were measured. Results The cirrhotic animals, but not the control animals, exhibited zinc deficiency. In both groups, there was positive immunoreactivity for type II and III cells and T1R2 receptors. The cirrhotic animals had no immunoreactivity for T1R3 receptors. Scanning electron microscopy analysis of the cirrhotic group revealed a uniform tapering of the gustatory papillae. Conclusion In conclusion the experimental cirrhosis model mimicked the biochemical and histological parameters of human cirrhosis, therefore enabling a study of the gustatory papillae and taste buds.

RESUMO Contexto As complicações inerentes de cirrose incluem a desnutrição proteico-calórica e deficiências de micronutrientes. Alterações no paladar são prejudiciais para o estado nutricional e o mecanismo para explicar essas mudanças não é bem documentada nos pacientes cirróticos. Objetivo Avaliar as papilas gustativas de ratos cirróticos. Métodos Foram avaliados 14 ratos Wistar machos. Após 16 semanas, o fígado foi removido para diagnosticar histologicamente cirrose, e o sangue foi colhido para efetuar testes de integridade hepática. A língua foi removida para exame histológico e imuno-histoquímica utilizando anticorpos contra o gene da proteína PGP 9.5 e os receptores de sabor doce T1R2 e T1R3. As alterações morfológicas foram determinadas por microscopia eletrônica de varredura e os níveis de zinco no soro foram medidos. Resultados Os animais cirróticos, em relação aos animais controle, apresentaram deficiência de zinco significativa. Em ambos os grupos, houve imunorreatividade positiva para o tipo II e células III e receptores T1R2. Os animais cirróticos não tinham imunoreactividade para receptores T1R3. Microscopia eletrônica de varredura do grupo cirrótico revelou um afilamento uniforme das papilas gustativas. Conclusão O modelo de cirrose experimental imitou os parâmetros bioquímicos e histológicos de cirrose humana, portanto, permitindo um estudo das papilas gustativas e paladar.

ALTERATION OF TASTE BUDS IN EXPERIMENTAL CIRRHOSIS. Is there correlation with human hypogeusia?

BACKGROUND: The inherent complications of cirrhosis include protein-calorie malnutrition and micronutrient deficiencies.Changes in taste are detrimental to the nutritional status, and the mechanism to explain these changes is not well documented in the cirrhotic patients. OBJECTIVE: To evaluate the taste buds of cirrhotic rats. METHODS: Fourteen male Wistar rats were evaluated. After 16 weeks, the liver was removed to histologically diagnose cirrhosis, and blood was collected to perform liver integrity tests. The tongue was removed for histological examination and immunohistochemistry using antibodies against protein gene product PGP 9.5 and the sweet taste receptors T1R2 and T1R3. Morphological changes were determined by scanning electron microscopy. Serum zinc levels were measured. RESULTS: The cirrhotic animals, but not the control animals, exhibited zinc deficiency. In both groups, there was positive immunoreactivity for type II and III cells and T1R2 receptors. The cirrhotic animals had no immunoreactivity for T1R3 receptors. Scanning electron microscopy analysis of the cirrhotic group revealed a uniform tapering of the gustatory papillae. CONCLUSION: In conclusion the experimental cirrhosis model mimicked the biochemical and histological parameters of human cirrhosis, therefore enabling a study of the gustatory papillae and taste buds.

Diethylnitrosamine-induced cirrhosis in Wistar rats: an experimental feasibility study.

The experimental models of the development of cirrhosis in rats require a long time. Many studies in animals have demonstrated similarities in histological pattern with human cirrhosis. Just like the relation between cirrhosis and increased lipid peroxidation (LPO), which contributes to the worsening of the disease. However, few studies have focused on the reduction of time to establish cirrhosis and evaluated the expression of heat-shock protein 70 (HSP70) in cirrhotic livers of rodents. The present study proposes the adaptation of an experimental cirrhosis model using diethylnitrosamine (DEN). Twenty-six male Wistar rats, weighing ±270 g, divided into two groups: (i) CO-control and (ii) DEN-diethylnitrosamine. The DEN group received 50 mg/kg of DEN twice a week intraperitoneally for 7 weeks. The model developed cirrhosis in 7 weeks. The liver function tests showed that the animals with DEN-induced cirrhosis had increased levels when compared to control. The histological examination showed changes in the liver architecture, with severe ductal proliferation, signs of chronic damage, cholestasis, lymphocytic infiltrate, steatosis, and extensive parenchymal loss. We also found nodular formations with homogeneous pattern, increased LPO, increased expression of iNOS, TGF beta, α-SMA, and NQO1. However, the HSP70 expression was reduced in cirrhotic animals. This study showed signs of cirrhosis in liver based on biochemical, histological, and molecular analysis. The reduced expression of HSP70 appears to be associated with increased oxidative stress, contributing to the worsening of the disease.

Oxidative stress and cell damage in a model of precancerous lesions and advanced hepatocellular carcinoma in rats.

Hepatocellular carcinoma (HCC) is the third most frequent cause of cancer deaths throughout the world. This study was aimed to analyze oxidative stress and cell damage in a multistage model of liver carcinogenesis induced by diethylnitrosamine (DEN) in rats. Male Wistar rats weighing 145-150 g were divided into three groups: control, precancerous lesions (PL) (which received 100 mg DEN once a week every 6 weeks up to 28 weeks), and advanced HCC (50 mg DEN once/twice per week up to 19 weeks). Lipid peroxidation (TBARS), superoxide dismutase (SOD) activity, and expression of transforming growth factor-1 beta (TGF)-1ß, endothelial and inducible nitric oxide syntahese (eNOS, iNOS), NADPH quinone oxireductase (NQO)-1, nuclear factor erythroid 2-related factor (NrF)2, kelch-like ECH-associated protein (Keap)1 and heat shock protein (HSP)70 were measured. TBARS concentration was augmented in the PL and advanced HCC groups. SOD activity, TGF-1ß and Nrf2 expression were higher in animals with precancerous lesions. In advanced HCC, expression of NQO1 and iNOS increased while there was a decrease in HPS70 expression. Data obtained provide evidence for the differential activation of proteins involved in oxidative stress and cell damage during progression of carcinogenesis in an animal model of HCC.