Calcitriol decreases TGF-β1 and angiotensin II production and protects against chlorhexide digluconate-induced liver peritoneal fibrosis in rats

Peritoneal fibrosis is a major complication of peritoneal dialysis that can lead to ultrafiltration failure. This study investigates the protective effects of calcitriol on chlorhexidine digluconate-induced peritoneal fibrosis in rats. Peritoneal fibrosis was induced in Sprague-Dawley rats by daily administration of 0.5 mL 0.1% chlorhexidine digluconate in normal saline via peritoneal dialysis for 1 week. Rats received daily intravenous injections of calcitriol (low-dose, 10 ng/kg; or high-dose, 100 ng/kg) for 1 week. After 7 days, conventional 4.25% Dianeal (30 mL) was administered via peritoneal dialysis over 4 h. Peritoneal solute transport was calculated from the dialysate concentration relative to its concentration in the initial infused dialysis solution (D₄/D_{0 glucose}) for glucose, and the dialysate-to-plasma concentration ratio (D₄/P_{4 urea}) at 4 h for urea. Rats were then sacrificed and the liver peritoneum was harvested for immunohistochemical analysis via microscopy. After dialysis, the D₄/P_{4 Urea} level was reduced; increases were observed in the D₄/D_{0 glucose} level and the levels of active transforming growth factor-β1 and angiotensin II in serum and dialysate; the liver peritoneum and muscle peritoneum was markedly thickened, and the expression of α-SMA, fibronectin, collagen, vascular endothelial growth factor, angiotensin II, transforming growth factor-β1, and phosphorylated Smad2/3 (P-Smad2/3)-positive cells in the liver peritoneum was elevated in the peritoneal fibrosis group compared with the vehicle group. Calcitriol decreased the serum and dialysate active transforming growth factor-β1 and angiotensin II level, decreased the thickness of the liver peritoneum and muscle peritoneum, and decreased the expression of α-SMA, fibronectin, collagen, vascular endothelial growth factor, angiotensin II, transforming growth factor-β1, and P-Smad2/3-positive cells in liver peritoneum cells. High-dose calcitriol exhibited better protective effects against peritoneal fibrosis than did the lower dose. Calcitriol protected against chlorhexidine digluconate-induced peritoneal fibrosis in rats by decreasing transforming growth factor-β1 and angiotensin II production.     

Histopathology and cytotoxicity as biomarkers in treated rats with cadmium and some therapeutic agents

The present study aimed to investigate the protective role of ascorbic acid (vitamin C) and zinc (Zn) against cadmium (Cd) induced histopathological changes in tissues of liver, kidney, lung and testis of rats as well as chromosomal aberrations. For this purpose, 60 male albino rats were divided into six groups; each group contained 10 animals. The first group served as control and was given only distilled water. The second and third groups received distilled water supplemented with 2 g ascorbic acid/l and 500 mg Zn/l, respectively. The fourth group received a daily oral dose containing 3 mg Cd/kg b.w. (1/30 LD₅₀). The fifth group received Cd + ascorbic acid (3 mg Cd/kg b.w. + 2 g ascorbic acid/l), while the sixth group received Cd + Zn (3 mg Cd/kg b.w. +500 mg Zn/l). The treatment in all groups lasted for 90 consecutive days. Rats exposed to cadmium showed severe histopathological changes in the liver, kidney, lung and testicular tissues as well as chromosomal aberrations such as: break, ring, centromeric separation and polyploidy. Co-treatment with zinc partially improved the histopathological changes and chromosomal aberrations while co-treatment with vitamin C exhibited a more protective role and markedly reduced tissues damage induced by Cd.     

Quercetin in vesicular delivery systems: Evaluation in combating arsenic-induced acute liver toxicity associated gene expression in rat model

Arsenic, the environmental toxicant causes oxidative damage to liver and produces hepatic fibrosis. The theme of our study was to evaluate the therapeutic efficacy of liposomal and nanocapsulated herbal polyphenolic antioxidant Quercetin (QC) in combating arsenic induced hepatic oxidative stress, fibrosis associated upregulation of its gene expression and plasma TGF ß (transforming growth factor ß) in rat model.A single dose of Arsenic (sodium arsenite-NaAsO₂, 13 mg/kg b.wt) in oral route causes the generation of reactive oxygen species (ROS), arsenic accumulation in liver, hepatotoxicity and decrease in hepatic plasma membrane microviscosity and antioxidant enzyme levels in liver. Arsenic causes fibrosis associated elevation of its gene expression in liver, plasma TGF ß (from normal value 75.2 ± 8.67 ng/ml to 196.2 ± 12.07 ng/ml) and release of cytochrome c in cytoplasm. Among the two vesicular delivery systems formulated with QC, polylactide nanocapsules showed a promising result compared to liposomal delivery system in controlling arsenic induced alteration of those parameters. A single dose of 0.5 ml of nanocapsulated QC suspension (QC 2.71 mg/kg b.wt) when injected to rats 1 h after arsenic administration orally protects liver from arsenic induced deterioration of antioxidant levels as well as oxidative stress associated gene expression of liver. Histopathological examination also confirmed the pathological improvement in liver. Nanocapsulated plant origin flavonoidal compound may be a potent formulation in combating arsenic induced upregulation of gene expression of liver fibrosis through a complete protection against oxidative attack in hepatic cells of rat liver.     

Effect of Bacopa monniera on liver and kidney toxicity in chronic use of opioids

In the present study, we investigated the protective effect of Bacopa monniera, an indigenous Ayurvedic medicinal plant in India, against morphine-induced liver and kidney toxicity in rats. Morphine intoxicated rats received 10-160 mg/kg body weight of morphine hydrochloride intraperitoneally for 21 days. Bacopa monniera Extract (BME) pretreated rats were administered with BME (40 mg/kg) orally once a day 2 h before the injection of morphine for 21 days. Pretreatment with BME has shown to possess a significant protective effect against morphine-induced liver and kidney functions in terms of serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, alkaline phosphatase, lactate dehydrogenases and gamma-glutamyl transferase activities and urea, creatinine and uric acid level respectively. Histopathological changes of liver and kidney were also in accordance with the biochemical findings. The results of this study indicate that Bacopa monniera extract exerted a protection against morphine-induced liver and kidney toxicity.     

Protective effects of pre-germinated brown rice diet on low levels of Pb-induced learning and memory deficits in developing rat

Lead (Pb) is a known neurotoxicant in humans and experimental animals. Numerous studies have provided evidence that humans, especially young children, and animals chronically intoxicated with low levels of Pb show learning and memory impairments. Unfortunately, Pb-poisoning cases continue to occur in many countries. Because the current treatment options are very limited, there is a need for alternative methods to attenuate Pb toxicity. In this study, the weaning (postnatal day 21, PND21) rats were randomly divided into five groups: the control group (AIN-93G diet, de-ionized water), the lead acetate (PbAC) group (AIN-93G diet, 2 g/L PbAC in de-ionized water), the lead acetate + WR group (white rice diet, 2 g/L PbAC in de-ionized water; PbAC + WR), the lead acetate + BR group (brown rice diet, 2 g/L PbAC in de-ionized water; PbAC + BR) and the lead acetate + PR group (pre-germinated brown rice diet, 2 g/L PbAC in de-ionized water; PbAC + PR). The animals received the different diets until PND60, and then the experiments were terminated. The protective effects of pre-germinated brown rice (PR) on Pb-induced learning and memory impairment in weaning rats were assessed by the Morris water maze and one-trial-learning passive avoidance test. The anti-oxidative effects of feeding a PR diet to Pb-exposed rats were evaluated. The levels of reactive oxygen species (ROS) were determined by flow cytometry. The levels of 8-hydroxy-2-deoxyguanosine (8-OHdG), γ-aminobutyric acid (GABA) and glutamate were determined by HPLC. Our data showed that feeding a PR diet decreased the accumulation of lead and decreased Pb-induced learning and memory deficits in developing rats. The mechanisms might be related to the anti-oxidative effects and large amount of GABA in PR. Our study provides a regimen to reduce Pb-induced toxicity, especially future learning and memory deficits in the developing brain.     

Rapid determination of 25-hydroxy vitamin D3 in swine tissue using an isotope dilution HPLC-MS assay

A rapid method for quantification of 25-hydroxy vitamin D3 in different swine tissues based on isotope dilution HPLC-MS has been developed and validated. Six times deuterated analyte is used as internal standard. The method is fast and can be performed with only 1 g sample. Sample preparation for kidney, liver, muscle and spleen requires only homogenisation and extraction with methanol. An additional enzymatic digest is required for skin, and clean-up of the extract by solid-phase extraction (SPE) is used for adipose tissue and skin. The lower limit of detection varies from 1 ng/g (muscle) to 5 ng/g (adipose and skin). The method has been successfully applied to various tissue samples of pigs fed for 119 days either 2000 IU of vitamin D3 or 50 μg of 25-hydroxy vitamin D3 per kg feed. For animals ingesting 25-OH-D3 supplements the highest tissue contents were observed in the skin (24.8 ± 3.5 ng/g), followed by kidney (14.2 ± 1.5 ng/g), liver and muscle (5.7 ± 0.6 ng/g). The 25-OH-D3 content in the skin was significantly higher in animals ingesting 2000 IU/kg of vitamin D3 (39.5 ± 13.4 ng/g). Levels in selected tissues of some animals were below the lower limit of quantification. No measurable amounts of 25-OH-D3 were found in spleen, abdominal fat and subcutaneous fat of the animals of both groups as well as in the liver, kidney and muscle of the animals ingesting 2000 IU/kg of vitamin D3.     

Study of the therapeutic effects of Lactobacillus and α-lipoic acid against dimethylnitrosamine-induced liver fibrosis in rats

Lactobacillus (LB) and α-lipoic acid (ALA) were investigated to compare their protective effects against dimethylnitrosamine (DMN)-induced liver fibrosis in rats. Animals were either injected intraperitoneally with DMN to induce hepatic fibrosis, or were left untreated (negative control). For the DMN + LB and DMN + ALA treatment groups, at two weeks of DMN treatment LB or ALA was added to the feed and supplementation continued until the experimental endpoint at sixty days. At the study endpoint, expression of IL-1β, IL-6, IL-10, TNF-α, IFN-γ, TGF-β1, COL1-α1 genes and the concentration of glutathione and malondialdehyde were measured in liver tissues, while GOT, GPT, and ALP concentrations were measured in blood. Body weights remained higher in NC and DMN + LB groups compared to DMN and DMN + ALA groups, while activity of GOT and GPT in serum was lower in DMN + LB and DMN + ALA groups compared to the DMN group. Compared to other treatment groups, in the DMN group expression of both TGF-β1 and, COL1-α1 mRNAs and pro-inflammatory cytokines increased, while that of 1L-10 decreased. Furthermore, LB and ALA treatments increased antioxidant activity of glutathione and decreased malondialdehyde in comparison to the DMN group. Between LB and ALA treatments, glutathione concentration was higher in the DMN + LB group, while malondialdehyde was lower. Our results indicate that both LB and ALA exert hepatoprotective effects against DMN-induced liver fibrosis. Their beneficial effects may be partly associated with down-regulation of both TGF-β1 and COL1-α1 signaling, which may be accounted for reduction of increased oxidative stress and TNF-α production.     

Comparative assessment of the effects of salinomycin and monensin on the biodistribution of lead and some essential metal ions in mice,subjected to subacute lead intoxication

In this study, we present a comparative assessment of the effects of two polyether ionophorous antibiotics (monensin and salinomycin) on the concentrations of lead (Pb), cooper (Cu), zinc (Zn) and iron (Fe) in the kidneys, spleen, liver and brain of Pb-intoxicated animals. Our data demonstrated that the intoxication of ICR male mice with Pb salt resulted in a significant accumulation of Pb in all studied organs of the mice compared to the untreated control animals. The biodistribution of the toxic metal was in the order kidneys > spleen > liver > brain. The treatment of the Pb-intoxicated animals with tetraethylammonium salts of monensic and salinomycinic acids significantly decreased the concentration of the toxic metal ion compared to the toxic control. The effect varied in the interval 38% (for kidneys) to 52% (for brain) compared to the toxic control group (Pb). The tetraethylammonium salt of salinomycinic acid was more effective in reducing the Pb concentration in the brain of the Pb-treated mice compared to monensin. Pb-intoxication did not affect significantly the Zn endogenous concentration compared to the normal values. The treatment of ICR male mice with Pb-salt decreased the Cu concentration in the spleen and increased the Cu concentration in the liver compared to the untreated control animals. The detoxification of the Pb-intoxicated mice with tetraethylammonium salts of salinomycinic and monensic acids restored the Cu concentration in the spleen, but did not affect the Cu levels in the liver. The Pb-intoxication of the ICR mice resulted in a significant decrease of the Fe-concentration in the spleen and liver compared to the untreated control animals. The administration of the tetraethylammonium salts of salinomycinic and monensic acids to the Pb-treated animals restored the levels of Fe in both organs.     

Doxorubicin induced neuro- and cardiotoxicities in experimental rats: Protection against oxidative damage by Theobroma cacao Stem bark

80 rats, randomly selected, were divided into 3 treatment groups: pre-, co- and post-treatment; consisting of 6 sub-groups each (5 rats per sub-group): baseline, normal saline (2 mL), α-lipoic acid (20 mg/kg body weight), 200 mg/kg, 400 mg/kg or 800 mg/kg body weight Theobroma cacao stem bark aqueous extract (TCAE). All rats except for baseline group were intoxicated with 20 mg/kg body weight doxorubicin (DOX) intraperitoneally. The animals in pre- or post-treatment group received a single dose of DOX (20 mg/kg body weight) intraperitoneally 24 h before or after 7 days’ oral administration with TCAE respectively while those in co-treatment group were co-administered 2.86 mg/kg body weight of DOX with either normal saline, α- lipoic acid or TCAE orally for 7 days. Animals were sacrificed (pre- and post- treatment groups were sacrificed on the ninth day while the co-treatment group sacrificed on the 8th day). Brain and heart tissue samples were harvested for enzyme markers of toxicity, oxidative stress and histopathological examinations. DOX intoxication caused significant decrease in activities of LDH and ACP, and increase in γGT and ALP activities in brain tissues while causing a significant increase in LDH, ACP, γGT activities and decrease in ALP activity in the cardiac tissues. DOX intoxication caused a significant increase in concentrations of H₂O₂ generated, MDA and PC, XO, MPx and NOX activities with concomitant decrease in CAT, SOD, GPx and GST activities, and in concentrations of GSH, AsA and α-Toc in brain and cardiac tissues. Pre-, co- and post-treatment with TCAE at either 200 mg/kg, 400 mg/kg or 800 mg/kg body weight significantly reversed the oxidative damage to the organs induced by DOX-intoxication. The result affirmed that T. cacao stem bark aqueous extract protected against DOX induced oxidative damage in brain and cardiac tissues of experimental rats.     

Protective effect of omega-3 fatty acid against mercury chloride intoxication in mice

The aim of this study was to investigate the protective effect of omega-3 fatty acid in HgCI₂ toxicity in mice. Levels of malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO) and total sialic acid (TSA), and histopathological changes in selected organs were evaluated. Twenty-eight mice were equally divided into 4 groups, namely Groups I–IV. Group I animals received intraperitoneal (ip) injection of physiological saline solution; Group II animals received ip injection of 0.4 mg/kg/day HgCI₂; Group III animals received ip injection of 0.4 mg/kg/day HgCI₂ in addition to subcutaneous (sc) injection of 0.5 g/kg/day omega-3 fatty acid; and Group IV animals received sc injection of 0.5 g/kg/day omega-3 fatty acid. All treatments lasted 7 days. The levels of MDA, NO and TSA were significantly higher in Group II and lower in Groups III and IV as compared to the Group I. GSH level was the highest in Group IV. In histopathology, severe degeneration in liver and kidney was observed in Group II animals. These degrading changes were seen to be reduced greatly in Group III animals. The results suggested that omega-3 fatty acid might attenuate HgCI₂-induced toxicity by improving antioxidant status and acute phase response in mice.     

N-acetyl cysteine and selenium protects mercuric chloride-induced oxidative stress and antioxidant defense system in liver and kidney of rats: A histopathological approach

Mercury exposure is second-most common cause of metal poisoning which is quite stable and biotransformed to highly toxic metabolites thus eliciting biochemical alterations and oxidative stress. The aim of present study describes the protective effect of selenium either alone or in combination with N-acetyl cysteine (NAC) against acute mercuric chloride poisoning. The experiment was carried out in male albino Sprague Dawley rats (n = 30) which was divided into five groups. Group 1 served as control. Groups 2–5 were administered mercuric chloride (HgCl₂: 12 mol/kg, i.p.) once only, group 2 served as experimental control. Animals of groups 3, 4 and 5 were received N-acetyl cysteine (NAC: 0.6 mg/kg, i.p.) and selenium (Se: 0.5 mg/kg, p.o.) and NAC with Se in combination. Acute HgCl₂ toxicity caused significant rise in serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, albumin, bilirubin, γ-glutamyl transpeptidase, cholesterol, triglycerides, protein, urea, creatinine, uric acid and blood urea nitrogen content. Animals also showed significantly higher mercury content in liver and kidney, significant rise in lipid peroxidation level with concomitant decrease in reduced glutathione content and the antioxidant enzyme activities of superoxide dismutase and catalase after HgCl₂ exposure. Results of the present investigation clearly showed that combination therapy with NAC + Se provide maximum protection against mercury toxicity than monotherapy (alone treated groups) by preventing oxidative degradation of biological membrane from metal mediated free radical attacks.     

Redox status of the liver and kidney of 2,2-dichlorovinyl dimethyl phosphate (DDVP) treated rats

The effect of 2,2-dichlorovinyl dimethyl phosphate on redox homeostasis in male rats was investigated. Rats were grouped into four: A, B, C and D where A (the control) received orally 1 ml of distilled water; B, C and D (test groups) received orally 2.5, 5 and 10 mg/kg body weight of DDVP respectively for 28 days. DDVP administration significantly reduced (P < 0.05) the alkaline phosphatase activity in the liver and kidney with corresponding increases in the serum. Acid phosphatase activity increased significantly (P < 0.05) in liver and kidney, while there was no significant change (P > 0.05) in the serum acid phosphatase activity. There was also a significant decrease (P < 0.05) in the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase in the liver and kidney. Liver and kidney levels of GSH, vitamins C and E were also significantly reduced (P < 0.05). Serum malonidialdehyde and lipid hydroperoxide also increased significantly (P < 0.05) in all DDVP treated groups. The available data from this study revealed that DDVP brings about its toxicity through depletion of the antioxidant systems and thus exposing the cells and cellular macromolecules to oxidative attacks by reactive oxygen species generated either from its metabolites or other in vivo means.     

In vivo genotoxicity evaluation of a plant based antiarthritic and anticancer therapeutic agent Boswelic acids in rodents

The genotoxic potential of anti-inflammatory/anti-arthritic and anticancer plant based drug molecule Boswelic acids (BA) was studied by in vivo system. Systematic literature survey revealed that studies on the genotoxicity of BA are not available. Although reports on genotoxicity of Boswellia serrata dry extract and modified 3-O-acetyl-11-keto-β-boswelic acid are available and these studies were conducted in in vitro systems. The earlier general toxicity study of BA has been conducted by us, revealed it to be non toxic. The genotoxicity was carried out in Wistar rats using different cytogenetic assay system-abnormalities viz. chromosomal aberrations; sperm morphology, micronuclei and comet assays. Six groups of animals, each comprised of five rats, were taken for each study. Group1-4 received BA at 125, 250, 500 and 1000 mg/kg p.o., respectively prepared as 2% gum acacia suspension, fifth group received a positive control cyclophosphamide (CP) 40 mg/kg p.o. or metronedazole (MTZ) 130 mg/kg p.o. or mercuric chloride (HgCl₂) 0.864 mg/kg p.o. (as per the experiment requirement) whereas the sixth group kept as vehicle control. The results on the bases of the data obtained revealed that BA is quite safe as it did not show any genotoxicity at any dose level up to 1000 mg/kg. The positive controls used in different experiments showed highly significant abnormal cytogenetic changes in comparison to the control group.     

Safety of Prunus africana and Warburgia ugandensis in asthma treatment

The aim of the study was to determine the possible cytotoxicity of the aqueous stem bark extracts of Prunus africana and Warburgia ugandensis to Vero E6 cells and acute toxicity in BALB/c mice. Despite being some of the most popular medicinal plants used in Africa, little is known about the safety. In-vitro cytotoxicity tests on Vero E6 cells were investigated using MTT assay to assess the safety of the two plant extracts. Vero E6 cells on growing to confluence were incubated with different drug concentrations for 48 h for the drug to take effect. Viability of the cells was measured by a scanning multiwell spectrophotometer, color intensity being equivalent to viable cells which reduce MTT to soluble formazan crystals. This was done by determining the CC₅₀ of the extracts, CC₅₀ being the concentration of the dose of the compound/extract that kills 50% of the cells. In acute toxicity a total of 55 mice were used. Mice were divided into eleven groups of 5 mice, one group served as negative control and ten groups received oral gavage doses at 500, 889.56, 1581.6, 2812.15 or 5000 mg/kg body weight once. Mortality and other signs of toxicity were recorded within 24 h and the weights of the surviving mice taken for 14 days thereafter. P. africana had CC₅₀ of 104.08 μg/ml while W. ugandensis had CC₅₀ > 250 μg/ml and both were classified as not cytotoxic. There was no mortality observed in groups of mice that received P. africana extracts at 500 and 889.56 mg/kg body weight. There was 20%, 60% and 100% mortality observed within 24 h for mice that received P. africana extracts at 1581.64, 2812.15 and 5000 mg/kg body weight respectively. Lethal dose (LD₅₀) for P. africana was 2201.207 mg/kg body weight. W. ugandensis extracts had no mortality recorded in all dose levels and the LD₅₀ was > 5000 mg/kg body weight. The weights of mice that survived the entire 14 days in all groups increased and were not significantly different from that of controls p > 0.05. From the in vitro and in vivo studies, the two extracts were safe to use. Though with their customary value among many Kenyan communities in management of asthma among other ailments there is a need for further validation of any anti-asthmatic properties and responsible chemical compounds to augment the findings.     

Xanthohumol lowers body weight and fasting plasma glucose in obese male Zucker fa/fa rats

Obesity contributes to increased risk for several chronic diseases including cardiovascular disease and type 2 diabetes. Xanthohumol, a prenylated flavonoid from hops (Humulus lupulus), was tested for efficacy on biomarkers of metabolic syndrome in 4 week old Zucker fa/fa rats, a rodent model of obesity. Rats received daily oral doses of xanthohumol at 0, 1.86, 5.64, and 16.9 mg/kg BW for 6 weeks. All rats were maintained on a high fat (60% kcal) AIN-93G diet for 3 weeks to induce severe obesity followed by a normal AIN-93G (15% kcal fat) diet for the last 3 weeks of the study. Weekly food intake and body weight were recorded. Plasma cholesterol, glucose, insulin, triglyceride, and monocyte chemoattractant protein-1 (MCP-1) levels were assessed using commercial assay kits. Plasma and liver tissue levels of XN and its metabolites were determined by liquid–chromatography tandem mass spectrometry. Plasma and liver tissue levels of xanthohumol were similar between low and medium dose groups and significantly (p < 0.05) elevated in the highest dose group. There was a dose-dependent effect on body weight and plasma glucose levels. The highest dose group (n = 6) had significantly lower plasma glucose levels compared to the control group (n = 6) in male but not female rats. There was also a significant decrease in body weight for male rats in the highest dose group (16.9 mg/kg BW) compared to rats that received no xanthohumol, which was also not seen for female rats. Plasma cholesterol, insulin, triglycerides, and MCP-1 as well as food intake were not affected by treatment. The findings suggest that xanthohumol has beneficial effects on markers of metabolic syndrome.     

Lead in liver and kidney of exposed rats: Aging accumulation study

The concentration of lead in liver and kidneys of Wistar rats, fed with lead since fetal period in relation to their age and to a control group, was determined. A group of rats was exposed to lead acetate (n = 30) in drinking water and the other group was exposed to normal water (n = 20). Samples were collected from rats aging between 1 and 11 months and were analyzed by Energy Dispersive X-ray Fluorescence (EDXRF) without any chemical preparation. The EDXRF results were assessed by the PIXE (Proton Induced X-ray Emission) technique. The formaldehyde used to preserve the samples was also analyzed by ETAAS (Electro-Thermal Atomic Absorption Spectrometry) in order to verify if there was any loss of lead from the samples to the formaldehyde. We found that the loss was not significant (<2%).Concerning the mean values of the lead concentration measured in the contaminated soft tissues, in liver they range from 6 to 22 μg g^?1, and in kidneys from 44 to 79 μg g^?1. The control rats show, in general, values below the EDXRF detection limit (2 μg g^?1). The ratio kidney/liver ranges from 2 to 10 and is strongly positively correlated with the age of the animals. A Spearman correlation matrix to investigate the correlation between elemental concentrations and the dependence of these concentrations with age showed that there is a strong positive correlation with age for lead in the liver but not in the kidney. The correlation matrix showed also that the concentration of lead in these two soft tissues is not correlated. The lead accumulation in liver is made by different plateaus that strongly decrease with age. It was verified the existence of two levels of accumulation in kidney, not very highlighted, which might be indicative of a maximum accumulation level for lead in kidney.     

Effects of daily protein intake levels on the oral stereotypic behaviours in energy restricted lambs

Effects of daily protein intake levels on oral stereotypic behaviours (OSB) in energy restricted lambs were investigated. Thirty-eight male lambs were randomly allotted to three treatments. Lambs in the first group (AL) received their ration (12.1 MJ ME/kg DM; 148.6 g CP/kg DM) at ad libitum level, whereas the second group (RP1) (12.1 MJ ME/kg DM; 177.4 g CP/kg DM) and the third group (RP2) (12.1 MJ ME/kg DM; 214.9 g CP/kg DM) received their rations at restricted levels. Recording of behaviours was carried out once a week using time sampling technique during a 7-week experimental period. OSB were significantly (P<0.001) affected by the treatments. RP2 group showed higher oral stereotypies than the others. It was concluded that increasing the daily protein intake under energy restricted conditions may have additive effects on the development of stereotypic oral behaviours.     

Effects of Canarium odontophyllum leaves on plasma glucose and T lymphocyte population in streptozotocin-induced diabetic rats

Type 1 diabetes mellitus is a chronic disease characterized by lack of insulin production. Immune mechanisms are implicated in the pathogenesis of Type 1 diabetes. Canarium odontophyllum (CO) fruits and leaves have been shown to possess high antioxidant activity. This study was conducted to evaluate the effects of CO leaves aqueous extract on the blood glucose and T lymphocyte population in the spleen of streptozotocin (STZ)-induced diabetic rats. Nineteen male Sprague–Dawley rats were randomly divided into three groups: normal, diabetic control and CO treated diabetic groups. Diabetes was induced by a single intraperitoneal injection of 65 mg STZ/kg body weight. The extract of CO leaves was administered orally by force feeding daily at the dose of 300 mg/kg for 28 days. The rats were sacrificed at the end of the study and the spleen was harvested for flow cytometry analysis. The results showed a significant decrease in body weight of diabetic and CO treated diabetic groups compared with the normal group (p < 0.05). The fasting blood glucose level of CO treated diabetic group was significantly lower than the diabetic group (p < 0.05). Diabetic and CO treated diabetic groups showed a significant increase in the percentage of spleen CD3⁺ CD4⁺ T lymphocytes (p < 0.05) when compared with the normal group. However, there was no significant difference in the percentage of spleen CD3⁺ CD8⁺ T lymphocytes among all experimental groups. The finding suggested that an aqueous extract of CO leaves has the ability to reduce blood glucose levels in diabetic rats.     

The protective effect of montelukast sodium on carbon tetrachloride induced hepatopathy in rat

AimThis study investigates the effects of montelukast sodium (MK) (CysLTLT1 receptor antagonist) on CCl₄induced hepatopathy on rat.Material and methodsWe worked on 4 groups of 10 Wistar male rats each. The groups received as follows: group I (control group) – saline, group II – MK 5 mg/kg/day i.p. for 5 days, group III – MK 5 mg/kg/day i.p., 1 day prior to and 4 days concomitantly with CCl₄ p.o., 0.3 ml/Kg/day and group IV – CCl₄, p.o., 0.3 ml/Kg/day for 4 days. One day after the last administration, samples of blood were taken and alanine aminotransferase (ALT), total bilirubin (TB), direct bilirubin (DB), malondialdehyde (MDA), catalase (CAT) as well as total antioxidant capacity (TAC) were determined. The histopathological exam was performed. We also determined superoxide dismutase (SOD), MDA, CAT and GSH in liver homogenate.ResultsCompared to group IV, group III exhibited statistically significant lower levels of ALT (318 ± 15.75 versus 203.14 ± 10.28 UI, p < 0.0001), TB (3.16 ± 0.30 versus 1.99 ± 0.08 mg/dl, p < 0.0001), MDA in blood and in liver homogenate (4.98 ± 1.71 versus 2.15 ± 1.18 nmol/ml, p = 0.0004) and higher levels of SOD and CAT. Histopathologically, group IV presented important macro- and micro-vesicular hepatic steatosis and group III preserved lobular histoarchitecture and had less severe cellular lesions.ConclusionMK exhibits a partial hepatoprotective effect on rats treated with CCl₄.     

Effects of different selenium source on selenium distribution,loin quality and antioxidant status in finishing pigs

The experiment was conducted to study the effects of different selenium source on selenium distribution, loin quality and antioxidant status in finishing pigs. A total of 108 castrates (Duroc × Landrace × Yorkshire) at average body weight (BW) of 60 kg were allotted to three treatments, each of which was replicated three times with 12 pigs per replicate (four per pen). The control groups received the basal diet containing 0.045 mg Se/kg. A 0.3 mg Se/kg in forms of sodium selenite or selenomethionine was added to the basal diet for the experimental groups. The total test period was 40 d. Results showed that selenomethionine-treatment increased the Hunter a (redness) value of meat color during 45 min, 8 and 16 h measurement period (P<0.05) and decreased the drip loss of loin muscle during 8 and 16 h measurement period (P<0.05), while sodium selenite-treatment only elevated the Hunter a value of meat color during 0.75 h measurement period (P<0.05) and had no significant effects on drip loss of loin muscle tissues. Both selenomethionine and sodium selenite-treatment increased the Se content in serum, muscle, liver, pancreas and kidney tissue (P<0.05), the level was substantially higher in muscle, liver and pancreas (P<0.05) in the selenomethionine treated group. In addition, both selenomethionine and sodium selenite-treatment increased glutathione peroxidase (GSH-Px) activity (P<0.05) and decreased the malondialdehyde (MDA) content in the liver and muscle (P<0.05) when compared with control group, but the level of magnitude was higher when selenomethionine was fed. The present study suggests that compared with sodium selenite, selenomethionine is more effective in depositing Se in tissues, enhances the antioxidant status, thus decreasing the volume of drip loss and stabilizing the meat color.