Higher Relative Liver Weight Research Articles

Effects of intramuscularly injected plant-derived antimicrobials in the mouse model

With increasing antibiotic resistance, the use of plant derived antimicrobials (PDAs) has gained momentum. Here, we investigated the toxicity of trans-cinnamaldehyde, eugenol, and carvacrol after intramuscular injection in mice. Two doses of each PDA—300 and 500 mg/kg body weight—and vehicle controls were injected into the muscle of the right hind limb of CD-1 adult mice (n = 8/treatment). Ten physical/behavioral parameters were monitored hourly for 2 h and twice daily for 4 days post-injection together with postmortem examination of leg muscles and organs. Within the first 2 days of carvacrol treatment, one male died in each dose level and a third male receiving 500 mg/kg was removed from the study. No mortality was seen with any other treatment. Among all 81 parameters examined, significant higher relative liver weights (300 and 500 mg/kg eugenol groups; P < 0.05) and relative kidney weights (300 mg/kg carvacrol group; P < 0.001) were observed. Taken together, little to mild toxicity was seen for trans-cinnamaldehyde and eugenol, respectively, while carvacrol exerted more toxicity in males. This study lays the foundation for future extensive work with large sample size, varied treatment durations, and additional treatment levels.

The development of nonalcoholic steatohepatitis is subjected to breeder dependent variation in guinea pigs

Variability in disease development due to differences in strains and breeders constitutes a substantial challenge in preclinical research. However, the impact of the breeder on non-alcoholic steatohepatitis (NASH) is not yet fully elucidated. This retrospective study investigates NASH development in guinea pigs from Charles River or Envigo fed a high fat diet (20% fat, 15% sucrose, 0.35% cholesterol) for 16 or 24/25 weeks. Charles River animals displayed more severe NASH, with higher steatosis (p < 0.05 at week 16), inflammation (p < 0.05 at both week), fibrosis (p < 0.05 at week 16) and disease activity (p < 0.05 at both weeks). Accordingly, alanine and aspartate aminotransferase were increased at week 24/25 (p < 0.01). Hepatic expression of inflammatory (Ccl2, Cxcl8) and fibrotic (Pdgf, Serpine1, Col1a1) genes was also increased (p < 0.05). Differences were observed in healthy chow (4% fat, 0% sucrose, 0% cholesterol) fed animals: Envigo animals displayed higher relative liver weights (p < 0.01 at both weeks), liver cholesterol (p < 0.0001 at week 24/25) and aspartate aminotransferase (p < 0.05 at week 16), but lower levels of alkaline phosphatase (p < 0.0001 at week 24/25). These findings accentuates the importance of the breeder and its effect on NASH development and severity. Consequently, this may affect reproducibility, study comparison and limit the potential of developing novel therapies.

Sex Differences in Metabolic Responses to Chronic Immobilization Stress in Rats

Abstract Background Responses to stress could range from homeostatic variations to life-threatening effects depending on the type, timing and severity of the applied stimulus. Gender is accompanied by variations in oxidative stress, which causes the development of metabolic diseases. Under physiological conditions, females were found to be less susceptible to oxidative stress. Aim of work: This study was conducted to highlight the sex differences in the metabolic responses to chronic immobilization stress in rats, and to elucidate the possible underlying mechanisms. Materials and Methods Forty adult Wistar rats of both sexes; were randomly divided into 2 main groups: control group and stressed group, each of which was further subdivided into male and female groups. Stressed groups were exposed to chronic immobilization for 4 weeks. All rats were subjected to determination of body mass index, visceral fat weight, absolute and relative weights of liver and pancreas, plasma glucose, glucose uptake by diaphragm, glucose output by kidneys, lipid profile and plasma levels of insulin, leptin and sex hormones, malodialdehyde (MDA), total antioxidant capacity (TAC) and nitrite. HOMA-B and HOMA-IR were calculated. Also, caspase 3 was assessed in pancreas by immunohistochemistry. Results Stressed male rats showed lower BMI, higher relative liver weight, dyslipidemia, fasting hyperglycemia, higher glucose output by kidneys, lower glucose uptake by diaphragm, HOMA-B and plasma levels of insulin, testosterone and TAC and higher plasma estrogen and MDA levels compared to the control male group. Compared to the control female group, stressed female rate exhibited hyperglycemia, hypoinsulinemia, dyslipidemia, oxidative stress, higher plasma sex hormones. Compared to stressed male rats, stressed female group showed significantly higher BMI percentage change and plasma levels of TAC, estrogen and testosterone, but significantly lower absolute liver weight, glucose output by the kidneys, plasma levels of total cholesterol and triglycerides, and atherogenic index. Conclusion Chronic immobilization stress imposes greater hyperglycemic and hyperlipidemic status in males than in females. The altered sex hormonal pattern and lowered antioxidant defences could be contributory mechanisms

Effects of arginine on the growth performance, hormones, digestive organ development and intestinal morphology in the early growth stage of layer chickens

The objective of this study was to investigate the effects of arginine on the growth performance, hormones, digestive organ development and intestinal morphology of chicks of laying hens. A total of three hundred 1-d-old male Lohmann Brown chicks were randomly assigned to five groups, each with six replicate sets of 10 birds. The five groups were fed different diets containing 1.19, 1.44, 1.69, 1.94 or 2.19% arginine from 1 d to 42 d of age. The results showed that dietary levels of arginine had a significant effect on body weight at 14, 28 and 42 d (p < .05). The insulin-like growth factor-I (IGF-I) concentration in serum was significantly increased with increasing levels of dietary arginine (p < .05). With the increase in dietary arginine, chicks had a higher relative liver weight (p < .05). Levels of 1.94 and 2.19% dietary arginine had a more positive effect on the length (p < .05) and relative weight of the small intestine (p < .05), respectively. The morphology of the duodenal mucosa and the villus height of the ileum in chicks were significantly affected by the dietary arginine levels (p < .05). This study suggested that 1.44% dietary arginine provided the maximum body weight of layer chickens during their early development by increasing the villus height in both the duodenum and ileum, whereas 2.19% dietary arginine inhibited the growth of the chicks via a shorter villus height in the intestinal mucosa and excessive serum IGF-I.

Chronic DON exposure and acute LPS challenge: effects on porcine liver morphology and function

The aim of the present study was to examine the role of chronic deoxynivalenol (DON) exposition on the liver morphology and function in combination with pre- and post-hepatic lipopolysaccharide (LPS) stress in young pigs fed for 4 weeks with a DON-contaminated diet (4.59 mg/kg feed). At the end of the experiment, LPS (7.5 μg/kg BW) was administered for 1 h pre-hepatically (Vena portae hepatis) or post-hepatically (Vena jugularis). Liver morphology was macroscopically checked and showed haemorrhage in all LPS groups, significantly higher relative liver weights, accompanied by marked oedema in the gallbladder wall. Histological changes were judged by a modified histology activity index (HAI). Liver HAI score was significantly increased in all LPS groups compared to placebo, primarily due to neutrophil infiltration and haemorrhage. DON feed alone was without effect on the liver HAI. Liver function was characterized by (i) hepatic biochemical markers, (ii) mitochondrial respiration and (iii) Ca2+ accumulation capacity of isolated mitochondria. Clinical chemical parameters characterizing liver function were initially (<3 h) slightly influenced by LPS. After 3 h, bilirubin and alkaline phosphatase were increased significantly, in DON-fed, jugular-infused LPS group. Respiration and Ca2+ accumulation capacity of isolated liver mitochondria was not impaired by chronic DON exposure, acute LPS challenge or combined treatments. DON-contaminated feed did not change macroscopy and histology of the liver, but modified the function under LPS stress. The different function was not linked to modifications of liver mitochondria.

A chronic oral exposure of pigs with deoxynivalenol partially prevents the acute effects of lipopolysaccharides on hepatic histopathology and blood clinical chemistry

Lipopolysaccharides (LPS), a cell wall component of gram-negative bacteria, and deoxynivalenol (DON), a prevalent Fusarium-derived contaminant of cereal grains, are each reported to have detrimental effects on the liver. A potentiating toxic effect of the combined exposure was reported previously in a mouse model and hepatocytes in vitro, but not in swine as the most DON-susceptible species. Thus, pigs were fed either a control diet (CON) or a Fusarium contaminated diet (DON, 3.1mg DON/kg diet) for 37 days. At day 37 control pigs were infused for 1h either with physiological saline (CON_CON), 100μg/kg BW DON (CON_DON), 7.5μg/kg BW LPS (CON_LPS), or both toxins (CON_DON/LPS) and Fusarium-pigs with saline (DON_CON) or 7.5μg/kg BW LPS (DON_LPS). Blood samples were taken before and after infusion (−30, +30, +60, +120, and +180min) for clinical blood chemistry. Pigs were sacrificed at +195min and liver histopathology was performed. LPS resulted in higher relative liver weight (p<0.05), portal, periportal and acinar inflammation (p<0.05), haemorrhage (p<0.01) and pathological bilirubin levels (CON_CON 1.0μmol/L vs. CON_LPS 5.4μmol/L, CON_DON/LPS 8.3μmol/L; p<0.001). DON feeding alleviated effects of LPS infusion on histopathology and blood chemistry to control levels, whereas DON infusion alone had no impact.

Developmental changes of carcass composition, meat quality and organs in the Jinhua pig and Landrace

The present study was aimed to compare the developmental changes of carcass composition, meat quality characteristics and organ weight in pigs of different breeds. Six pigs (sex balance) of each breed were slaughtered at 35, 80 and 125 days of age, respectively. The carcass was chilled and the left carcass side was dissected into bone, lean meat, fat and skin; additionally, organ weight and meat quality parameters were observed. Carcasses of the Jinhua pig were lighter (P < 0.001), contained less lean meat percentage (P < 0.01) and more carcass fat percentage (P < 0.05) than did carcasses of the Landrace. L*-values were lower in Jinhua pigs than in Landrace at 125 days of age (P < 0.05), but the Jinhua pig had higher a*-values compared with Landrace at the age of 80 days (P < 0.01) and 125 days (P < 0.01), respectively. In addition, Jinhua pigs showed lower colour scores (P < 0.05), higher intramuscular fat (IMF) percentage (P < 0.05), less marbling scores (P < 0.05) and lower drip loss (P < 0.05) than Landrace. For organ weight, Jinhua pigs had higher relative heart weight at the age of 80 days (P < 0.05) and 125 days (P < 0.001), and higher relative liver weight at 125 days of age (P < 0.01) than that of Landrace. In addition, the relative kidney weight was heavier (P < 0.001) in the Jinhua pig than in the Landrace during the whole experiment. These results indicated that developmental changes of carcass composition, meat quality parameters and organ weight displayed breed differences. Jinhua pigs were fatter than Landrace but the former had better quality characteristics in the meat.

The effect of high-fat and high-fructose diets on glucose tolerance and plasma lipid and leptin levels in rats.

High-fat and high-fructose diets are usually used to induce animal model diabetes mellitus. The purposes of this research were to compare the abnormalities of glucose metabolism caused by high-fructose diet and a high-fat diet and the effects of the high-fructose diet and high-fat diet on plasma leptin. In this research, 24 Sprague-Dawley rats were used as the experimental animals, which were divided into three groups: chow diet (control group), high-fructose diet (60% fructose w/w) and high-fat diet (20% lard w/w). They were fed for a period of 8 weeks, during which an oral glucose tolerance test was conducted in the seventh week, and after completion of the eighth week, the abdominal adipose tissue and liver of the rats were excised and weighed, and the plasma cholesterol, triglyceride, insulin and leptin concentrations were assayed. The high-fat diet group presented a fasting blood glucose concentration that was higher than that of the control group. Furthermore, after 2 h of glucose challenge, the rats in the high-fat and high-fructose diet groups all presented higher plasma glucose concentrations than did the control group. The high-fat diet group showed higher body weight, higher relative liver weight, a higher plasma cholesterol concentration and higher amylase activity than did the other groups, whereas the high-fructose diet group showed higher fasting insulin and triglyceride concentrations. As for adipose tissue, the high-fat diet group presented an amount that was higher than that of the high-fructose and control groups, but the plasma leptin concentration of the high-fructose group was higher than that of the control group. It can be concluded from the above-mentioned experimental results that a high-fructose diet can cause hyperinsulinaemia, while a high-fat diet can result in impaired pancreatic function of insulin secretion and glucose intolerance, indicating that high-fructose diet and a high-fat diet may exert divergent effects on glucose metabolism in rats.

Toxicity of oxidized fats II: tissue levels of lipid peroxides in rats fed a thermally oxidized corn oil diet

Male Wistar albino rats were fed for 21 days on a diet in which fat (12%) was included either as fresh corn oil, malonaldehyde content=0.11±0.05 μg/g (control) or thermally oxidized corn oil, malonaldehyde content=0.20±0.03 μg/g (experimental) and the tissue levels of lipid peroxides in six organs—namely, liver, kidney, brain, heart, lungs and testes—were determined. Of the organs studied, significantly ( P<0.1) higher concentrations of lipid peroxides were observed only in the liver and kidney of the experimental rats. In the course of the feeding, the experimental rats showed significantly ( P<0.1) lower gains in body weights as well as higher relative liver weights than the control rats.

Canthaxanthin and Excess Vitamin A Alter α-Tocopherol, Carotenoid and Iron Status in Adult Rats

beta-Carotene and excess vitamin A have been shown to reduce plasma alpha-tocopherol when fed to young rats. The present study assessed the effects of beta-carotene, excess vitamin A and canthaxanthin (4,4'-diketo-beta-carotene) on carotenoid, alpha-tocopherol and iron status in adult retired breeder rats. Male 8- to 10-mo-old rats (10/group) were fed varying levels of vitamin A as retinyl palmitate, beta-carotene and canthaxanthin ad libitum for 8 wk. The AIN-76A diet was modified to contain 16% (wt/wt) fat and 50% carbohydrate (control) plus beta-carotene or canthaxanthin at 0, 0.048 (BC1 or CX1) and 0.2% (BC2 or CX2) of the diet. These compounds were fed with and without excess retinyl palmitate (RP, 220 mg/kg). Higher relative liver weights were observed in CX- and RP-fed groups. Plasma retinyl esters were detected in all RP-fed groups. Plasma retinyl palmitate was 1.6- and 1.5-fold higher in RP-BC and RP-CX groups, respectively, than in the RP groups. Plasma and liver beta-carotene and canthaxanthin were 11-54% and 26-74% lower, respectively, with excess retinyl palmitate feeding. Feeding canthaxanthin and retinyl palmitate but not beta-carotene, resulted in lower levels of plasma alpha-tocopherol. Liver non-heme iron levels were also lower in CX-fed rats irrespective of retinyl palmitate feeding. These results extend to adult rats previous findings that excess retinyl palmitate alters vitamin E and carotenoid status prior to the manifestation of clinical signs of hypervitaminosis A. Additionally, canthaxanthin feeding lowers alpha-tocopherol and iron status in adult rats.

Carbohydrate in rainbow trout diets. III. Growth and chemical composition of fish from different families fed four levels of carbohydrate in the diet

Groups of rainbow trout ( Salmo gairdneri) from five different families and five inbred groups were fed four diets similar in protein and energy content but differing in the percentage of metabolizable energy present as carbohydrate. The percentage of metabolizable energy from carbohydrate was 15, 26, 37 and 49%, respectively. Significant differences between fish families were found for growth, condition factor, chemical composition of the fish, relative liver wight, liver colour, digestibility of energy and N-free extracts, dressing percentage amount of intestinal fat and flesh colour. Interaction between diet and family was significant for relative liver weight and liver colour. There was no interaction between diet and family for growth, indicating that the prospects for selectively breeding a strain of rainbow trout specifically better able to utilize carbohydrate are not promising. Growth rate and condition factor increased with decreasing carbohydrate level in diet. The fish fed high levels of carbohydrate had less dry matter, fat and ash in the body, and higher percentage carbohydrate in the liver. They also had higher relative liver weights and more discoloured livers. The fish fed high levels of carbohydrate had significantly better apparent digestibility of energy and protein. There were no significant differences in mortality rate between the groups, and veterinary examination did not reveal any pathological differences in the fish fed different feeding regimes.

Increased hepatic glycogen synthetase and decreased phosphorylase in trained rats.

Rats were either physically trained by a 12 wk swimming program or were freely eating or weight matched, sedentary controls. Trained rats had a higher relative liver weight and total hepatic glycogen synthetase (EC 2.4.1.11) activity and a lower phosphorylase (EC 2.4.1.1) activity than the other groups of rats. These changes may partly explain the demonstrated training-induced increase in glucose tolerance. None of the findings could be ascribed to differences in foold intake or body weight.

Effect of diet on the hepatotoxicity of polybrominated biphenyls (FireMaster PB-6).

The consumption of diets formulated with Cruciferae vegetables, e.g., cauliflower, cabbage, and Brussels sprouts, has been shown to result in a stimulation of the intestinal and hepatic microsomal enzyme systems in rats. This study was designed to determine if this increase in intestinal and hepatic microsomal enzyme activity affected the hepatic response to polybrominated biphenyls (PBB). After three weeks of consuming either a semipurified or 25% cauliflower leaf-supplemented diet (CLD), male Sprague-Dawley rats were maintained for an additional 20 days on their respective diets containing either 0, 1, or 50 ppm PBB. A significant decrease in body weights, but not feed efficiency, was observed over all levels of PBB in animals consuming CLD compared to semipurified diets; consumption of up to 50 ppm of PBB had no effect on body weights with either diet. Relative liver weights (RLW), hepatic aryl hydrocarbon hydroxylase (AHH), N- and O-demethylase, as well as intestinal AHH were all increased in CLD-consuming animals before the addition of PBB. While PBB supplementation alone resulted in increased RLW, hepatic AHH, N- and O-demethylase, microsomal protein, and cytochrome P-450, rats consuming cauliflower diets + PBB had even higher RLW and N- and O-demethylase activity and microsomal protein concentrations. Hepatic PBB residue and total hepatic lipids were significantly reduced in CLD groups receiving 50 ppm PBB. These results suggest that the antitoxic effects of certain vegetables are related to more rapid metabolism and excretion of xenobiotic compounds.

Effect of Diet on the Hepatotoxicity of Polybrominated Biphenyls (FireMaster PB-6)

The consumption of diets formulated with Cruciferae vegetables, e.g., cauliflower, cabbage, and Brussels sprouts, has been shown to result in a stimulation of the intestinal and hepatic microsomal enzyme systems in rats. This study was designed to determine if this increase in intestinal and hepatic microsomal enzyme activity affected the hepatic response to polybrominated biphenyls (PBB). After three weeks of consuming either a semipurified or 25% cauliflower leaf-supplemented diet (CLD), male Sprague-Dawley rats were maintained for an additional 20 days on their respective diets containing either 0, 1, or 50 ppm PBB. A significant decrease in body weights, but not feed efficiency, was observed over all levels of PBB in animals consuming CLD compared to semipurified diets; consumption of up to 50 ppm of PBB had no effect on body weights with either diet. Relative liver weights (RLW), hepatic aryl hydrocarbon hydroxylase (AHH), N- and O-demethylase, as well as intestinal AHH were all increased in CLD-consuming animals before the addition of PBB. While PBB supplementation alone resulted in increased RLW, hepatic AHH, N- and O-demethylase, microsomal protein, and cytochrome P-450, rats consuming cauliflower diets + PBB had even higher RLW and N- and O-demethylase activity and microsomal protein concentrations. Hepatic PBB residue and total hepatic lipids were significantly reduced in CLD groups receiving 50 ppm PBB. These results suggest that the antitoxic effects of certain vegetables are related to more rapid metabolism and excretion of xenobiotic compounds.