Quantification of Superoxide Radical in the Brain of Rats with Experimentally Induced Obstructive Jaundice

The study aimed to directly measure in vivo superoxide radical (O₂⁻) a direct indicator of oxidative stress, in the brain of rats with experimentally induced obstructive jaundice by employing a new quantitative ultrasensitive fluorescent assay requiring minimum sample. O₂⁻ anion is specific for dihydroethidine (DHE) and upon reaction gives a characteristic product, namely 2-OH-ethidium. Ten male rats underwent laparotomy and were divided into two groups: I, sham operated and II bile duct ligation. Ten days later, following injection with DHE (a O₂⁻ trap), all animals were killed and samples from cerebral cortex, midbrain and cerebellum were removed for analysis. It was shown that compared to group I, in group II the O₂⁻ was increased by 67% in the cerebral cortex and by 37% in the midbrain as a consequence of experimental obstructive jaundice, while its levels were unaffected in the cerebellum. The data in this experimental obstructive jaundice model imply a region-specific increase of O₂⁻ formation rate, being higher in cerebral cortex, less so in the midbrain and not at all in cerebellum.     

Protective effect of quercetin on liver damage induced by biliary obstruction in rats

The aim of this study was to evaluate the possible protective effects of quercetin (QE) against cholestatic oxidative stress and liver damage in the common bile duct ligated rats. A total of 24 male Wistar albino rats were divided into three groups: control, bile duct ligation (BDL) and BDL + received QE; each group contain 8 animals. The rats in QE treated groups were given QE (15 mg/kg) once a day intraperitoneally for 4 weeks starting 3 days prior to BDL operation. The changes demonstrating the bile duct proliferation and fibrosis in expanded portal tracts include the extension of proliferated bile ducts into lobules, mononuclear cells, and neutrophil infiltration into the widened portal areas were observed in BDL group. Treatment of BDL with QE attenuated alterations in liver histology. The alpha smooth muscle actin (α-SMA), transforming growth factor beta (TGF-β1) positive cells and the activity of TUNEL in the BDL were observed to be reduced with the QE treatment. The data indicate that QE attenuates BDL-induced cholestatic liver injury, bile duct proliferation, and fibrosis. The hepatoprotective effect of QE is associated with antioxidative potential.     

Effects of Ellagic Acid on Copper,Zinc, and Biochemical Values in Serum and Liver of Experimental Cholestatic Rats

Ellagic acid (EA) is a natural polyphenolic compound. Although, modulator effects of EA on copper (Cu) and zinc (Zn) levels in some liver diseases have been reported in experimental animals, its effects in obstructive jaundice (OJ) has not been clarified. We aimed to evaluate potential effects of EA on Cu and Zn levels in liver and serum of cholestatic rats. Forty Wistar albino rats were equally divided into four groups. First group was used as controls. Second group received EA (60 mg⁻¹ kg⁻¹ day⁻¹) for 8 days. Third was OJ group, and fourth group was OJ plus EA group. After 8 days, blood and liver samples were obtained. Higher serum and liver Cu and lower serum and liver Zn levels were found in OJ group (p < 0.05) compared with other groups. However, these differences reached to significant levels for Cu in serum and for Zn in lever. Higher serum copper levels were decreased, and lower liver Zn levels were increased by EA treatment in cholestatic rats (p < 0.05). Also, higher Cu/Zn ratio in OJ group was decreased by EA treatment both in liver (p < 0.05) and in serum (p < 0.05). Significantly higher serum bilirubin, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase values were found in OJ and OJ + EA groups compared with the control and EA groups (p < 0.05). In conclusion, result of the current study indicated that ellagic acid has modulator effects on Cu and Zn levels in liver and serum of cholestatic rats.     

Alpha-Tocopherol Decreases Iron-Induced Hippocampal and Nigral Neuron Loss

There are many studies about iron-induced neuronal hyperactivity and oxidative stress. Some reports also showed that iron levels rise in the brain in some neurodegenerative diseases such as Parkinson’s (PD) and Alzheimer’s disease (AD). It has been suggested that excessive iron level increases oxidative stress and causes neuronal death. Tocopherols act as a free radical scavenger when phenoxylic head group encounters a free radical. We have aimed to identify the effect of α-tocopherol (Vitamin E) on iron-induced neurotoxicity. For this reason, rats were divided into three groups as control, iron, and iron + α-tocopherol groups. Iron chloride (200 mM in 2.5 μl volume) was injected into brain ventricle of iron and iron + α-tocopherol group rats. Same volume of saline (2.5 μl) was given to the rats belonging to control group. Rats of iron + α-tocopherol group received intraperitoneally (i.p.) α-tocopherol (100 mg/kg/day) for 10 days. After 10 days, rats were perfused intracardially under deep urethane anesthesia. Removed brains were processed using standard histological techniques. The numbers of neurons in hippocampus and substantia nigra of all rats were estimated by stereological techniques. Results of present study show that α-tocopherol decreased hippocampal and nigral neuron loss from 51.7 to 12.1% and 41.6 to 17.8%, respectively. Findings of the present study suggest that α-tocopherol may have neuroprotective effects against iron-induced hippocampal and nigral neurotoxicity and it may have a therapeutic significance for neurodegenerative diseases involved iron.     

The efficiency of CAPE on retardation of hepatic fibrosis in biliary obstructed rats

The aim of this study was to evaluate the possible protective effects of caffeic acid phenethyl ester (CAPE) against cholestatic oxidative stress and liver damage in the common bile duct ligated rats. A total of 18 male Sprague–Dawley rats were divided into three groups: control, bile duct ligation (BDL) and BDL + received CAPE; each group contain 6 animals. The rats in CAPE treated groups were given CAPE (10 μmol/kg) once a day intraperitoneally (i.p) for 2 weeks starting just after BDL operation. The changes demonstrating the bile duct proliferation and fibrosis in expanded portal tracts include the extension of proliferated bile ducts into lobules, inflammatory cell infiltration into the widened portal areas were observed in BDL group. Treatment of BDL with CAPE attenuated alterations in liver histology. The proliferating cell nuclear antigen and the activity of TUNEL in the BDL were observed to be reduced with the QE treatment. The application of BDL clearly increased the tissue hydroxyproline (HP) content, malondialdehyde (MDA) levels and decreased the antioxidant enzyme (superoxide dismutase (SOD), glutathione peroxidase (GPx)) activities. CAPE treatment significantly decreased the elevated tissue HP content, and MDA levels and raised the reduced of SOD, and GPx enzymes in the tissues. The data indicate that CAPE attenuates BDL-induced cholestatic liver injury, bile duct proliferation, and fibrosis. The hepatoprotective effect of CAPE is associated with antioxidative potential.     

Effect of chromium supplementation on the diabetes induced-oxidative stress in liver and brain of adult rats

This study was designed to investigate the susceptibility of liver and brain tissues, as insulin-independent tissues, of normal adult male rats to the oxidative challenge of subchronic supplementation with chromium picolinate (CrPic) at low (human equivalent) and high doses (2.90 and 13.20 μg Cr kg⁻¹ day⁻¹, respectively). Also, the modulative effect of CrPic administration on the enhanced oxidative stress in the liver and brain tissues of alloxan-diabetic rats was studied. Fasting serum glucose level was not modified in normal rats but significantly reduced in diabetic rats that had received CrPic supplement. A mild oxidative stress was observed in the liver and brain of CrPic-supplemented normal rats confirmed by the dose-dependent reductions in the levels of hepatic and cerebral free fatty acids, superoxide dismutase and glutathione peroxidase activities, and in contrast increased tissue malondialdehyde concentration. On the other hand, hepatic and cerebral catalase activity was reduced in the high dose group only. CrPic supplementation did not act as a peroxisome proliferator confirmed by the significant reductions in liver and brain peroxisomal palmitoyl CoA oxidase activity. The non significant alterations in liver protein/DNA and RNA/DNA ratios indicate that CrPic did not affect protein synthesis per cell, and that mild elevations in hepatic total protein and RNA concentrations might be due to block or decrease in the export rate of synthesized proteins from the liver to the plasma. In diabetic rats, elevated levels of hepatic and cerebral free fatty acids and malondialdehyde, and in contrast the overwhelmed antioxidant enzymes, were significantly modulated in the low dose group and near-normalized in the high dose group. The significant increases observed in liver total protein and RNA concentrations, as well as protein/DNA and RNA/DNA ratios in diabetic rats supplemented with the high dose of Cr, compared to untreated diabetics, may be related to the improvement in the glycemic status of the diabetic animals rather than the direct effect of CrPic on protein anabolism.     

Sodium Tungstate Attenuate Oxidative Stress in Brain Tissue of Streptozotocin-Induced Diabetic Rats

High blood glucose concentration in diabetes induces free radical production and, thus, causes oxidative stress. Damage of cellular structures by free radicals play an important role in development of diabetic complications. In this study, we evaluated effects of sodium tungstate on enzymatic and nonenzymatic markers of oxidative stress in brain of streptozotocin (STZ)-induced diabetic rats. Rats were divided into four groups (ten rats in each group): untreated control, sodium tungstate-treated control, untreated diabetic, and sodium tungstate-treated diabetic. Diabetes was induced with an intraperitoneal STZ injection (65 mg/kg body weight), and sodium tungstate with concentration of 2 g/L was added to drinking water of treated animals for 4 weeks. Diabetes caused a significant increase in the brain thiobarbituric acid reactive substances (P < 0.01) and protein carbonyl levels (P < 0.01) and a decrease in ferric reducing antioxidant power (P < 0.01). Moreover, diabetic rats presented a reduction in brain glucose-6-phosphate dehydrogenase (21%), superoxide dismutase (41%), glutathione peroxidase (19%), and glutathione reductase (36%) activities. Sodium tungstate reduced the hyperglycemia and restored the diabetes-induced changes in all mentioned markers of oxidative stress. However, catalase activity was not significantly affected by diabetes (P = 0.4), while sodium tungstate caused a significant increase in enzyme activity of treated animals (P < 0.05). Data of present study indicated that sodium tungstate can ameliorate brain oxidative stress in STZ-induced diabetic rats, probably by reducing of the high glucose-induced oxidative stress and/or increasing of the antioxidant defense mechanisms.     

Protective effects of thymoquinone against cholestatic oxidative stress and hepatic damage after biliary obstruction in rats

The aim of this study was to examine the preventive and therapeutic effects of thymoquinone (TQ) against cholestatic oxidative stress and liver damage in common bile duct ligated rats. A total of 24 male Sprague–Dawley rats were divided into three groups: control, bile duct ligation (BDL) and BDL + received TQ; each group contain 8 animals. The rats in TQ treated groups were given TQ (50 mg/kg body weight) once a day orally for 2 weeks starting 3 days prior to BDL operation. To date, no more biochemical and histopathological changes on common bile duct ligated rats by TQ treatment have been reported. The application of BDL clearly increased the tissue hydroxyproline (HP) content, malondialdehyde (MDA) levels and decreased the antioxidant enzyme [superoxide dismutase (SOD), glutathione peroxidase (GPx)] activities. TQ treatment significantly decreased the elevated tissue HP content, and MDA levels and raised the reduced of SOD, and GPx enzymes in the tissues. The changes demonstrating the bile duct proliferation and fibrosis in expanded portal tracts include the extension of proliferated bile ducts into lobules, mononuclear cells, and neutrophil infiltration into the widened portal areas were observed in BDL group. Treatment of BDL with TQ attenuated alterations in liver histology. The immunopositivity of alpha smooth muscle actin and proliferating cell nuclear antigen in BDL were observed to be reduced with the TQ treatment. The present study demonstrates that oral administration of TQ in bile duct ligated rats maintained antioxidant defenses and reduces liver oxidative damage and ductular proliferation. This effect of TQ may be useful in the preservation of liver function in cholestasis.     

Nanoparticles of Selenium as Species with Stronger Physiological Effects in Sheep in Comparison with Sodium Selenite

The present study was designed to compare the effects of nano red selenium and sodium selenite on the antioxidative activities of neutrophils and the hematological parameters in sheep. Fifteen sheep were randomly allocated into three groups. Groups 1 and 2 received selenium nanoparticles orally at 1 mg/kg and sodium selenite at 1 mg Se/kg for 10 consecutive days; group 3 served as the control. To assess the degrees of oxidative stress and of lipid peroxidation of the cellular membranes, the levels of thiobarbituric acid reactive substances (TBARS) were determined in serum samples that were collected at different supplementation intervals, i.e., after 0, 10, 20, and 30 days. In addition, hematological parameters in the serum samples were measured by routine procedures. It was found that TBARS levels in groups 1 and 2 were significantly higher on days 20 and 30 compared to the basal level on day 0. It was also found that on day 30, the TBARS activities in both treated groups were significantly higher than those of the controls (P < 0.05). These findings may explain the seemingly paradoxical effects of supplemental selenium on the indicators of oxidative stress, as the levels of TBARS were generally expected to decrease in the presence of selenium. There were no significant differences between the PCV and RBC values in the three groups. The white blood cell count (WBC) in group 1 showed a significant increase on days 20 and 30 in comparison with the control group. However, in group 2, there was a significant increase of the WBC value just on day 20 in comparison with the control group. Also, there were significant increases of the neutrophil counts and significant decreases of the lymphocyte counts on day 10 in group 1, in comparison with those in group 2 and controls, and on days 20 and 30 in groups 1 and 2 in comparison with those in the control group.     

Enhanced bioremediation of soil contaminated with viscous oil through microbial consortium construction and ultraviolet mutation

This study focused on enhancing the bioremediation of soil contaminated with viscous oil by microorganisms and evaluating two strategies. Construction of microbial consortium and ultraviolet mutation were both effective applications in the remediation of soil contaminated with viscous oil. Results demonstrated that an interaction among the microorganisms existed and affected the biodegradation rate. Strains inoculated equally into the test showed the best remediation, and an optimal microbial consortium was achieved with a 7 days’ degradation rate of 49.22%. On the other hand, the use of ultraviolet mutation increased one strain’s degrading ability from 41.83 to 52.42% in 7 days. Gas chromatography and mass spectrum analysis showed that microbial consortium could treat more organic fractions of viscous oil, while ultraviolet mutation could be more effect on increasing one strain’s degrading ability.     

Evaluation of Fluoride-Induced Oxidative Stress in Rat Brain: A Multigeneration Study

Multigenerational evaluation was made in rats on exposure to high fluoride (100 and 200 ppm) to assess neurotoxic potential of fluoride in discrete areas of the brain in terms of lipid peroxidation and the activity of antioxidant enzyme system. The rats were given fluoride through drinking water (100 and 200 ppm) and maintained subsequently for three generations. Fluoride treatment significantly increased the lipid peroxidation and decreased the activity of antioxidant enzymes viz, catalase, superoxide dismutase, glutathione peroxidase, glutathione S-transferase, and glutathione level in first-generation rats and these alterations were more pronounced in the subsequent second and third-generation rats in both the doses tested. Decreased feed and water consumption, litter size and organ (brain) somatic index, marginal drop in body growth rate and mortality were observed in all three generations. Decreased antioxidant enzyme activity and increased malondialdehyde levels found in the present study might be related to oxidative damage that occurs variably in discrete regions of the brain. Results of this study can be taken as an index of neurotoxicity in rats exposed to water fluoridation over several generations.     

Dietary Supplementation with tBHQ,an Nrf2 Stabilizer Molecule,Confers Neuroprotection Against Apoptosis in Amyloid β-Injected Rat

Nuclear factor erythroid 2-related factor 2 (Nrf2) coordinates the up-regulation of cytoprotective genes via the antioxidant response element (ARE). There is significant evidence that oxidative stress is a critical event in the pathogenesis of AD. Considering the protective role of Nrf2 against oxidative injury, we studied to determine whether in vivo toxicity of amyloid β (Aβ) can be attenuated by tBHQ, an Nrf2 stabilizer, Using an Aβ injection model. We demonstrated that pre-activation of endogenous Nrf2 by tBHQ attenuated Aβ-induced caspase-3 expression. tBHQ enhanced GSH, decreased MDA level, and inhibited NF-κB. This investigation provides the first documentation of tBHQ’s neuroprotective effect through decrease of Aβ accumulation in rat brain. Our results show the involvement of Hsp-70 in this protective effect. In summary tBHQ treatment for 1 week prior to Aβ injection protected against the oxidative damage, apoptosis and Aβ accumulation in rats.     

Antioxidant-rich date palm fruit extract inhibits oxidative stress and nephrotoxicity induced by dimethoate in rat

Recent investigations have proved the crucial role of nutritional antioxidants to prevent the damage caused by toxic compounds. In this study, the antioxidant effect of date palm fruit extract on dimethoate-induced oxidative stress and nephrotoxicity in rat is investigated and compared with the effect of the well-known antioxidant vitamin C. Male Wistar rats were randomly divided into six groups of ten each: a control group (C), a group that received dimethoate (20 mg/kg body weight) (D), a group given Deglet Nour extract (DNE), a group treated with DNE 30 min before the administration of dimethoate (DNE + D), a group which received VitC (100 mg/kg body weight) plus dimethoate (Vit C + D), and a group given dimethoate for the first month and DNE 30 min after administration of dimethoate, during the second month (D + DNE). These components were daily administered by gavage for 2 months. After completing the treatment period, blood samples from rats were collected under inhaled diethyl ether anesthesia for serum urea, uric acid, and creatinine levels, while the rat kidneys were obtained for enzyme assays and histology. Oral administration of dimethoate in rats induced a marked renal failure characterized by a significant increase in serum creatinine and urea levels (p < 0.01) in addition to a significant decrease in serum uric acid (p < 0.05). Interestingly, these drastic modifications were accompanied by a marked enhancement of lipid peroxidation in kidney, indicating a significant induction of oxidative damage (p < 0.01) and dysfunctions of enzymatic antioxidant defenses. These biochemical alterations were also accompanied by histological changes in kidney revealed by a narrowed Bowman’s space, tubular degeneration, tubular cell desquamation, and tubular dilatation of proximal tubules. Treatment with date palm fruit extract (Deglet Nour) and also with vitamin C significantly (p < 0.05) reversed the serum renal markers to their near-normal levels when compared with dimethoate-treated rats. In addition, Deglet Nour extract and vitamin C significantly reduced lipid peroxidation, restored the antioxidant defense enzymes in the kidney, and improved the histopathology changes. The present findings indicate that in vivo date palm fruit may be useful for the prevention of oxidative stress-induced nephrotoxicity.     

Haemotoxicity of busulphan,doxorubicin, cisplatin and cyclophosphamide in the female BALB/c mouse using a brief regimen of drug administration

Many anticancer drugs are myelotoxic and cause bone marrow depression; however, generally, the marrow/blood returns to normal after treatment. Nevertheless, after the administration of some anti-neoplastic agents (e.g. busulphan, BU) under conditions as yet undefined, the marrow may begin a return towards normal, but normality may not be achieved, and late-stage/residual marrow injury may be evident. The present studies were conducted to develop a short-term mouse model (a ‘screen’) to identify late-stage/residual marrow injury using a brief regimen of drug administration. Female BALB/c mice were treated with BU, doxorubicin (DOX), cisplatin (CISPLAT) or cyclophosphamide (CYCLOPHOS) on days 1, 3 and 5. In ‘preliminary studies’, a maximum tolerated dose (MTD) for each drug was determined for use in ‘main studies’. In main studies, mice were treated with vehicle (control), low and high (the MTD) dose levels of each agent. Necropsies were performed, and blood parameters and femoral/humeral nucleated marrow cell counts (FNCC/HNCC) were assessed on six occasions (from days 1 to 60/61 post-dosing). Late-stage/residual changes were apparent in BU-treated mice at day 61 post-dosing: RBC, Hb and haematocrit were reduced, mean cell volume/mean cell haemoglobin were increased and platelet and FNCC counts were decreased. Mice given DOX, CISPLAT and CYCLOPHOS, in general, showed no clear late-stage/residual effects (day 60/61). It was concluded that a brief regimen of drug administration, at an MTD, with assessment at day 60/61 post-dosing was a suitable short-term method/screen in the mouse for detecting late-stage/residual marrow injury for BU, a drug shown to exhibit these effects in man.     

Time-related alterations of superoxide radical levels in diverse organs of bile duct-ligated rats

The time-related alterations of superoxide radical measured in vivo by employing an ultrasensitive fluorescent assay in the liver, intestine, kidney and brain of rats with experimentally induced obstructive jaundice was investigated. Eighteen rats were randomly divided into Group A, rats subjected to sham operation, and Group B, rats subjected to bile duct ligation (BDL). Three rats from each group were subsequently killed at different time points post-operatively (1, 5 and 10 days). As compared to sham-operated, BDL rats showed a gradual increase with time of superoxide radical in the intestine, liver, kidney and brain: for animals sacrificed on the 1^st, 5^th and 10^th day the increase was 45%, 50% and 96% in the liver, 76%, 81% and 118% in the intestine, 64%, 71% and 110% in the kidney and 76%, 95% and 142% in the brain, respectively. This study provides direct evidence of an early appearance of oxidative stress in diverse organs, implying a uniform systemic response to biliary obstruction and emphasizing the need of early bile flow restoration.     

Effect of fucoidan on aspirin-induced stomach ulceration in rats

In this study, the effects of fucoidan on aspirin-induced ulcers in rats were evaluated: both biochemical and immunological parameters were taken into consideration. The status of stomach tissue glycogen storage and histological changes were also examined. Examination of basic biochemical parameters showed significant (p < 0.01) alterations in aspartate (AST) and alanine (ALT) transaminases in ulcer-induced rats. Also, moderate alterations (p < 0.05) were observed in the levels of cholesterol and blood urea nitrogen (BUN). Histopathological examination showed neutrophil infiltration and inflammation in oxyntic cells with altered glycogen storage. Analysis of serum cytokines of aspirin-induced rats showed a moderate decrease in interleukin-10 (IL-10) with considerable increase of interleukin-6 (IL-6) and interferon-γ (INF-γ) when compared with control. Administration of fucoidan showed considerable (p < 0.05) protection against ulceration by inhibiting the acute alterations of AST, ALT, cytokines and stomach glycogen. However, aggravated serum INF-γ was observed in the fucoidan-pretreated group. These findings suggest that the anti-ulcer property of fucoidan might contribute in protecting the inflammatory cytokine-mediated oxidative damage to gastric mucosa.     

Protective Effect of Naringenin Against Lead-Induced Oxidative Stress in Rats

Oxidative stress is thought to be involved in lead-induced toxicity. The aim of this study was to investigate the possible protective role of naringenin on lead-induced oxidative stress in the liver and kidney of rats. In the present investigation, lead acetate (500 mg Pb/L) was administered orally for 8 weeks to induce hepatotoxicity and nephrotoxicity. The levels of hepatic and renal markers such as alanine aminotransferase, aspartate aminotransferase, urea, uric acid, and creatinine were significantly (P < 0.05) increased following lead acetate administration. Lead-induced oxidative stress in liver and kidney tissue was indicated by a significant (P < 0.05) increase in the level of maleic dialdehyde and decreased levels of reduced glutathione, superoxide dismutase, catalase, and glutathione peroxidase. Naringenin markedly attenuated lead-induced biochemical alterations in serum, liver, and kidney tissues (P < 0.05). The present study suggests that naringenin shows antioxidant activity and plays a protective role against lead-induced oxidative damage in the liver and kidney of rats.     

Responses of canopy duration to temperature changes in four temperate tree species: relative contributions of spring and autumn leaf phenology

While changes in spring phenological events due to global warming have been widely documented, changes in autumn phenology, and therefore in growing season length, are less studied and poorly understood. However, it may be helpful to assess the potential lengthening of the growing season under climate warming in order to determine its further impact on forest productivity and C balance. The present study aimed to: (1) characterise the sensitivity of leaf phenological events to temperature, and (2) quantify the relative contributions of leaf unfolding and senescence to the extension of canopy duration with increasing temperature, in four deciduous tree species (Acer pseudoplatanus, Fagus sylvatica, Fraxinus excelsior and Quercus petraea). For 3 consecutive years, we monitored the spring and autumn phenology of 41 populations at elevations ranging from 100 to 1,600 m. Overall, we found significant altitudinal trends in leaf phenology and species-specific differences in temperature sensitivity. With increasing temperature, we recorded an advance in flushing from 1.9 ± 0.3 to 6.6 ± 0.4 days °C⁻¹ (mean ± SD) and a 0 to 5.6 ± 0.6 days °C⁻¹ delay in leaf senescence. Together both changes resulted in a 6.9 ± 1.0 to 13.0 ± 0.7 days °C⁻¹ lengthening of canopy duration depending on species. For three of the four studied species, advances in flushing were the main factor responsible for lengthening canopy duration with increasing temperature, leading to a potentially larger gain in solar radiation than delays in leaf senescence. In contrast, for beech, we found a higher sensitivity to temperature in leaf senescence than in flushing, resulting in an equivalent contribution in solar radiation gain. These results suggest that climate warming will alter the C uptake period and forest productivity by lengthening canopy duration. Moreover, the between-species differences in phenological responses to temperature evidenced here could affect biotic interactions under climate warming.     

Gut regulatory peptides bombesin and neurotensin reduce hepatic oxidative stress and histological alterations in bile duct ligated rats

Gut regulatory peptides bombesin (BBS) and neurotensin (NT) exert a wide spectrum of biological actions on gastrointestinal tissues and we have previously shown that they improve intestinal barrier function and oxidative stress in experimentally jaundiced rats. In the present study, we explored their potential action on liver histology and oxidative status in bile duct ligated rats. Seventy male Wistar rats were randomly divided into five groups: controls, sham operated, bile duct ligated (BDL), BDL+BBS (10 μg/kg, s.c. ×3), BDL+NT (300 μg/kg, i.p.). At the end of the experiment, on day 10, serum total bilirubin and alanine aminotransferase (ALT) levels were determined and endotoxin was measured in portal and aortic blood. Liver tissue samples were examined histologically for evaluation of the ratio of portal tracts presenting changes of obstructive cholangiopathy and neutrophils' number in portal tracts. In addition, hepatic oxidative status was estimated on liver homogenates by measurements of lipid peroxidation (malondialdehyde), protein oxidation (protein carbonyl groups) and thiol redox state [reduced glutathione (GSH), oxidized glutathione (GSSG), total non-protein mixed disulfides (NPSSR) and protein thiols (PSH)]. Administration of BBS or NT significantly reduced portal and aortic endotoxaemia observed in obstructive jaundice. Both agents significantly ameliorated liver injury, as demonstrated by improvement of obstructive cholangiopathy and reduction of ALT. This effect was accompanied by prevention of lipid peroxidation, protein oxidation and decrease of the oxidized forms GSSG and NPSSR. Moreover, neutrophil accumulation in portal tracts was significantly decreased. In conclusion, this study shows that gut regulatory peptides BBS and NT reduce cholestatic liver injury, exerting protective effects on portal tract architecture, neutrophil infiltration and hepatic oxidative stress in bile duct ligated rats.