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The aim of this study was to evaluate the combination of maximum replacement of fishmeal (FM) and fish oil (FO) by alternative meals (AM) and oils (AO) to develop nutritious, but more eco-friendly diets for European sea bass ( Dicentrarchus labrax ) juveniles. European sea bass of 9.8 ± 1.5 g and 9.1 ± 0.5 cm were fed nine isonitrogenous (45% crude protein) and isolipidic (21%) diets containing gradually reduced levels of FM and FO as follows (%FM/%FO): 58/15, 20/6, 20/3, 10/6, 10/3, 5/6, 5/3 and 0/0. Another diet, 0/0 + , was similar to the 0/0 but supplemented with LC-PUFA from microbial and marine sources. After 90 days of feeding, European sea bass fed the 0/0 diet showed reduced (P + diet). Reduction of FM/FO down to 5/3 did not significantly affect fish survival or condition factor, whereas reduction to 5/6 did neither affect sea bass length or feed conversion and reduction down to 10/3 did not affected body weight, DGI and perivisceral fat or visceral weight. FM reductions down to 5% significantly reduced growth rate. FO substitution by vegetable oils (VO) led to reduced growth and increased liver to body weight ratios, liver lipid deposition and hepatocellular size. In liver and muscle, FO substitution increased n-6 fatty acids (FA) and n-6/n-3 ratio and reduced saturated FA and n-3 LC-PUFA, whereas monounsaturated FA were not increased in proportion to dietary contents. Moreover, FO reduction increased the products from Δ6 desaturase and elongases, Elovl6 and Elovl5. In conclusion, the results of this study show that it is possible to reduce dietary FM and FO levels down to 10% and 3% in mostly plant-based diets without affecting growth performance of European sea bass juveniles.

A 10-week feeding trial was conducted to evaluate the necessity of supplementing selenium (Se) in a low-protein basal diet for Australian snapper Pagrus auratus , a slower-growing fish species. Dietary Se supplementation was tested against commercial barramundi diet, most commonly fed to Australian snapper. Se-yeast was added to a reconstituted commercial diet and to a formulated basal diet at 0, 0.8 and 1.0 mg/kg Se to form six isoenergetic test diets to evaluate the effects of diet types, dietary Se supplementation and their interaction on the growth, feed utilisation, body composition and liver morphology of juvenile Australian snapper. These Se supplementation levels resulted in total dietary Se levels of 0.92, 1.68, 1.76, 1.67, 2.59 and 2.77 mg/kg, respectively. Each test diet was fed to triplicate groups of Australian snapper in a flow-through seawater system. There were no significant interaction between diet types and Se supplementation on all tested parameters of the snapper. Regardless of the diet types, snapper fed 1.0 mg/kg Se-supplemented diet attained significantly lower growth rate than the fish fed diets supplemented with 0 and 0.8 mg/kg of Se. Feed conversion ratio was significantly increased in snapper fed diets supplemented with 1.0 mg/kg Se. There were no effects of both diet types and Se supplementation on the proximate composition of the muscle and whole-body except the reduced moisture and gross energy levels in the whole-body of snapper fed 1.0 mg/kg Se-supplemented diet. The Se contents in the muscle and liver tissues showed positive linear relationships with dietary Se levels. Fish fed diet supplemented with 1.0 mg/kg Se showed increased hepatic lipid compared with the fish fed 0 and 0.8 mg/kg Se-supplemented diets. Histopathological alterations were observed in liver tissues of snapper fed the basal diet containing 2.77 mg/kg Se. The results concluded that the protein and Se requirements of Australian snapper are low and can be met by lower protein ingredients with the endogenous Se. Further, the dietary Se threshold level in Australian snapper fed a basal diet was 2.77 mg/kg, whereas this level was only 1.76 mg/kg in the reconstituted commercial diet.

As the roll-out of antiretroviral therapy continues to drive downwards morbidity and mortality in people living with HIV/AIDS (PLWHAs), organ toxicities (especially the liver) are frequently becoming a major concern for researchers, scientists and healthcare planners.This study was conducted to investigate the possible protective effect of Hypoxis hemerocallidea (AP) against highly active antiretroviral therapy (HAART)-induced hepatotoxicity. A total of 63 pathogen-free adult male Sprague-Dawley rats were divided into 9 groups and treated according to protocols.While no mortality was reported, animals treated with adjuvant HAART and AP recorded least% body weight gain. Significant derangements in serum lipid profiles were exacerbated by treatment of with AP as LDL (increased p

Aims In this work, we aimed to evaluate the effects of the Leishmania infantum chagasi infection on the liver of vaccinated mice, considering parameters of tissue damage and the inflammatory response elicited by vaccination. Main methods We used recombinant LPG3 protein (rLPG3) as immunogen in BALB/c mice before challenge with promastigote forms of L. infantum chagasi. The animals were separated into five groups: NI: non-infected animals; NV: non-vaccinated; SAP: treated with saponin; rLPG3: immunized with rLPG3; rLPG3 + SAP: immunized with rLPG3 plus SAP. The experiment was conducted in replicate, and the vaccination protocol consisted of three subcutaneous doses of rLPG3 (40 μg + two boosters of 20 μg). The mice were challenged two weeks after the last immunization. Key findings Our results showed that rLPG3 + SAP immunization decreased the parasite burden in 99 %, conferring immunological protection in the liver of the infected animals. Moreover, the immunization improved the antioxidant defenses, increasing CAT and GST activity, while reducing the levels of oxidative stress markers, such as H2O2 and NO3/NO2, and carbonyl protein in the organ. As a consequence, rLPG3 + SAP immunization preserved tissue integrity and reduced the granuloma formation, inflammatory infiltrate and serum levels of AST, ALT, and ALP. Significance Taken together, these results showed that rLPG3 vaccine confers liver protection against L. infantum chagasi in mice, while maintaining the liver tissue protected against the harmful inflammatory effects caused by the vaccine followed by the infection.

A wide range of endocrine disrupter chemicals can mimic steroid hormones causing adverse health effects. Nonylphenol (NP) and t-octhylphenol (t-OP) are man-made alkylphenolic environmental contaminants possessing controversial endocrine disruption properties. This study has investigated the effects of NP and t-OP enriched diets on hepatic tissue and biotransformation activities in the liver. To this aim, sea bream juveniles were fed with commercial diet enriched with three different doses of NP (NP1: 5mg/kg bw, NP2: 50mg/kg bw and NP3: 100mg/kg bw) or t-OP (t-OP1: 5mg/kg bw, t-OP2: 50mg/kg bw and t-OP3: 100mg/kg bw) for 21 days. A significant increase of the hepatosomatic index was observed in NP1 and t-OP1. Alteration of liver morphology was observed in both NP and t-OP exposed juveniles although the most altered endpoints were observed in t-OP2 with 100% of tissue degeneration. Ethoxyresorufin-O-deethylase activity was significantly inhibited by NP and t-OP (p0.05), while catalase activity was significantly induced, at both doses. A different pattern of protein expression of different isoforms of both vitellogenin and zona radiata protein was evidenced within the treatments. In addition, a significant increase in the abundance of the stress induced heat shock protein 70 gene in the liver of t-OP2 fish and a significant increase in the abundance of the estrogen induced cathepsin D gene in the liver of NP1 and t-OP2 fish, were observed. Finally, estradiol-17β (E2) and testosterone (T) plasma levels and E2/T showed significantly different patterns in NP and t-OP exposed against control fish.

Summary Objective The aim of this study was to identify the effects of strength training on plasma parameters, body composition and the liver of ovariectomized rats. Methods Wistar sedentary (SHAM), ovariectomized (OVX), and ovariectomized trained rats (strength training [OVX-EXE]) of 85% of one maximal repetition (1 RM), three times per week, for 10 weeks, were used on this study. We monitored the body weight and visceral (uterine, mesenteric and retroperitoneal) and subcutaneous adiposity, total cholesterol, triglycerides, HDL, blood glucose and liver morphology to identify the presence of macrovesicular steotosis (haematoxylin and eosin staining). Results We observed that strength training changed body weight (SHAM 293.0 ± 14.5 g; OVX 342.6 ± 10.8 g; OVX-EXE 317.7 ± 11.9 g, P Conclusions Considering the data obtained in this research, we emphasise the use of strength exercise training as a therapeutic means to combat or control the metabolic disturbances associated with menopause, including adiposity, and adverse changes in blood glucose, blood HDL and macrovesicular steatosis.

Cimicifuga racemosa (black cohosh) is a herbaceous perennial plant, that has been traditionally used for a variety of ailments (dyspepsia, climacteric complaints, muscular rheumatisms, menstrual cramps). From laboratory and clinical studies, black cohosh seems to have a relatively good safety profile, even if a number of case reports of hepatotoxicity were a matter of recent concern. Aim A number of case reports indicated that C. racemosa could induce hepatotoxicity. We evaluated the effects of black cohosh extract on liver morphology, and on levels of various hepatic function indices in rats. Methods Wistar rats received 300 mg/kg/day of C. racemosa extract by gavage, for 30 days. Biochemical analysis of serum was conducted by an automated, random-access clinical chemistry analyzer. Liver samples were used for hystomorphological and immunohistochemical examination, for the detection of apoptosis (TUNEL assay), and for the determination of GSH level (spectrophotometrical analysis). Results C. racemosa extract does not affect liver morphology and hepatic function indices, in rats. Conclusions On the basis of experimental data, the use of 300 mg/kg/day of black cohosh appears quite safe in rats. Nevertheless, in humans the safety of C. racemosa should be further monitored, in terms of patient-related factors.

Cold liver preservation in the University of Wisconsin solution (UW) followed by reperfusion alters hepatic parenchyma and extra cellular matrix. In this study we analyzed the benefit of adding either 500 µM Sodium Nitroprusside (NPNa) or 100 µM S-nitrosoglutathione (GSNO) as Nitric Oxide (NO) donors to the UW solution to prevent hepatic injury. Wistar adult rat livers were stored in UW solution (0oC) for 48Hs and reperfused (60 minutes) in the isolated perfused rat liver model (IPRL). Untreated livers were used as normal controls. Livers perfused but not preserved were used as controls of reperfusion. Parenchyma damages were evaluated by Hematoxylin-Eosin stain. Picrosirius Red and Gordon-Sweets stains were used for collagen and reticulin networks, respectively. An inmunohistochemistry assay for albumin was used as functional test. Cold preservation step was followed by swollen hepatocytes with “light empty halos” surrounding the nucleus, conserved hepatocyte cords and many rounded endothelial cells. The addition of NPNa or GSNO into UW solution, avoid these alterations. Livers preserved for 48 Hs and then reperfused showed extended areas of vacuolation around central veins, and many endothelial cells were rounded and located inside sinusoidal lumens. The collagen network was disorganized while the reticulin one was less altered. Albumin was distributed preferentially in pericentral areas. On the contrary, livers preserved in presence of NPNa or GSNO did not show vacuolation and both collagen and reticulin networks were unchanged. Albumin was more homogeneously distributed in both groups. In conclusion, the addition of 500 µM NPNa or 100 µM GSNO as a NO donor, improves UW solution properties to preserve rat livers by maintaining the hepatic morphology and avoiding hepatic injury post-cold preservation/reperfusion.

Sucrose acetate isobutyrate (SAIB), a mixture of esters of sucrose with a composition approximating the name sucrose diacetate hexaisobutyrate, has been used for over 30 yr in many countries as a 'weighting' or 'density-adjusting' agent in non-alcoholic carbonated and non-carbonated beverages. As part of the demonstration of safety of SAIB as a direct food additive in human diets, a program of toxicity testing was started in the late 1950s that culminated in extensive studies of SAIB in rodents, monkeys and humans over the last decade. This review summarizes the toxicity data, accrued up until 1988, that precede the safety studies published elsewhere in this issue. SAIB has been shown to have very low acute and chronic toxicities in rats, monkeys, and, except for effects on the liver, in dogs at feeding levels of up to 10% in the diet. Slight effects seen in rats and monkeys at levels of 10% in the diet are unlikely to be directly caused by exposure to SAIB. In dogs, however, SAIB causes decreases in bromosulfophthalein (BSP) and indocyanine green (ICG) elimination from the serum immediately following a single dose, indicative of interference with biliary excretion. On repeated feeding in dogs, SAIB caused increases in serum alkaline phosphatase levels, but enzymes indicative of toxic effects on the liver were unaffected. On prolonged feeding to dogs, SAIB caused changes in liver morphology revealed by electron microscopy. All of these effects were reversed when SAIB was withdrawn from the diet. The no-effect level for these effects in dogs was near 5 mg/kg body weight, but these effects were not seen in rats fed up to 4 g/kg body weight/day, monkeys fed up to 10 g/kg body weight/day, or humans fed up to 20 mg/kg body weight/day. The toxicity and pharmacological studies in dogs, rats and monkeys suggest that the effect of SAIB on biliary excretion and liver morphology in dogs is essentially pharmacological rather than toxicological in nature and that the difference between the effects in dogs at levels as low as 5 mg/kg body weight/day, and the lack of effects in rats or monkeys at levels up to 10 g/kg/day is not merely a quantitative difference between species, but an absolute qualitative difference.

This retrospective study of fatal passenger car crash victims in northern Sweden compares 396 multiple-vehicle (MV) and 201 single-vehicle (SV) fatalities from 1980 through 1989. Compared to MV fatalities, SV victims were more frequently males, were younger, were more often inebriated, had higher blood alcohol concentrations, had a higher frequency of fatty liver, and were less often restrained. The SV fatalities occurred most often from May through October, from Fridays through Sundays, and from 9 p.m. to 6 a.m. The road surface was usually dry, especially for drunken SV drivers. The SV drivers also more often lacked a valid driver's license. The study confirms that alcohol is one of the most important factors associated with traffic fatalities, particularly in SV crashes. More than half (56%) of the SV victims were inebriated by alcohol (MV, 11%), had a mean blood alcohol concentration of 1.9 g/l (MV, 1.6 g/l), and one-third had a fatty liver (MV, 20%). We also found a relation between fatty liver and increased blood alcohol concentrations, suggesting that studies regarding the role of alcohol in traffic fatalities should also include an evaluation of liver morphology.

Although the general liver morphology is similar in all mammals, there are some structural features in apparently healthy laboratory rodents. These peculiarities are known to be influenced by a great variety of endogenous and exogenous factors. Incidence, intensity, development and disappearance of such elements as extramedullary haemopoiesis, polyploidy, intranuclear and intracytoplasmic inclusions depend markedly upon genetics, age, hygienic condition, hormonal regulation and nutrition of the animals. It is concluded from this short review that the term "normal histology" should only be understood as being relative and that it may only be applied to a given, well defined animal population held under well defined conditions.

The effects of 2 recently developed trypanocidal agents, Diamidinophenylindol (DAPI) and Diimidazolinophenylindol (DIPI) at doses of 10-30 micrograms/g intraperitoneally (i.p.) on serum GOT, GPT and sorbitol dehydrogenase (SDH) levels and on liver morphology have been investigated in mice. Pentamidine served as reference drug. Both agents caused dose-dependent increases in serum transaminases and SDH, and discrete morphological changes of the liver, e.g., fatty degenerations, azinoperipheral vacuolisation and alterations of the nuclei, at least at the higher dosage.

Summary In liver biopsy specimens from patients with normal liver morphology (n = 11), fatty liver (n = 9), chronic hepatitis (n = 12) or cirrhosis (n = 3) the total glutathione and GSH-S-transferase activities towards an aryl and an epoxide substrate were measured. As compared to livers without pathomorphological changes there was a tendency to higher values for glutathione in the groups with definite liver diseases. Lower activities were seen in these pathological groups for the aryl transferase whereas epoxide transferase activity was only detectable in 7 out of 35 specimens. In post-mortem specimens (n = 58) of human livers with and without histopathological alterations no clearcut differences were found for glutathione and GSH-S-transferases except that there was a tendency to lower aryl transferase activities in livers with tumour metastases, whereas the epoxide transferase activities seemed to be higher.

1. 1. Morphological changes were found in livers of rats and chicks after acute poisoning with ethylene dibromide (EDB). 2. 2. In rats, EDB induced sinusoidal dilations and centrilobular necrosis, beginning from 8 hr after poisoning. 3. 3. In chicks the central areas were almost unchanged and portal areas were found to be affected by EDB; the concentration of eosinophilic granulocytes was much greater in EDB-treated livers than in controls.

Rats receiving 100 ppm, p,p′-DDT in their drinking water for a period of 45 days show reduced basophilia of the centrilobular liver cells. The basophilic fragments are scattered throughout the cytoplasm in most of these cells. The animals receiving 100 ppm PTU in their drinking water show similar morphological changes. The animals receiving p,p′-DDT plus PTU exhibit advanced changes involving almost all the cells of the inner two-thirds of the hepatic lobule. The ergastoplasm is reduced to a few small fragments located near the cell membrane. The remainder of the cytoplasm is very clear and foamy in appearance. It is considered that the changes in the liver induced by p,p′-DDT are potentiated by the effect of PTU on the hypophyso-thyroid system. This view is supported by our previous findings in the liver of surgically thyroidectomized p,p′DDT-receiving rats.