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Abstract\nHIGHLIGHTSMesoporous bioactive glass, with its versatile characteristics and morphology, holds significant potential as an ideal hemostatic material. However, limited data is available regarding its toxicity levels. Consequently, this research intends to assess the acute and repeated dose dermal toxicity of Mesoporous antibacterial bioactive glass microsphere impregnated nonwoven surgical cotton gauze (MABGmscg) dressing in albino Wistar rats, following the standards set by the Organization for Economic Cooperation and Development. In the acute dermal toxicity study, the impact of MABG (@2000mg/kg BW) mscg dressing was assessed following a single dermal application in both male and female Wistar rats (n = 10). Mortality, clinical signs, body weight fluctuations and gross observations were consistently monitored over a14 day period following the single dose. The results indicated that, MABG (@2000mg/kg BW) mscg dressing upon dermal exposure did not cause any adverse effect in acute dermal toxicity study in Wistar rats compared to control group. Given that 2000 mg/kg BW of MABG was deemed a nontoxic dose, a repeated dose dermal toxicity study of MABGmscg dressing was subsequently conducted at three dose levels (@200, 500, 1000 mg/kg BW) over 28 consecutive days in Wistar rats. During the study period, no unscheduled deaths occurred, and there were no clinical signs associated with treatment, body weight variations or abnormal gross findings at necropsy in any groups. The analysis concluded that, MABGmscg dressing is safe to be considered as a hemostatic dressing at the various tested dose levels in Wistar rats.A dressing composed of mesoporous antibacterial bioactive glass impregnated into nonwoven surgical cotton gauze (MABGmscg) has been developed to serve as an effective hemostatic material.The acute and repeated dose dermal toxicity study of MABGmscg dressing has been performed in Wistar ratsNo visible changes or systemic effects were observed after applying the MABGmscg dressing at different doses for 28 consecutive days in Wistar rats.Therefore, the MABGmscg dressing is considered safe for use as a hemostatic gauze.A dressing composed of mesoporous antibacterial bioactive glass impregnated into nonwoven surgical cotton gauze (MABGmscg) has been developed to serve as an effective hemostatic material.The acute and repeated dose dermal toxicity study of MABGmscg dressing has been performed in Wistar ratsNo visible changes or systemic effects were observed after applying the MABGmscg dressing at different doses for 28 consecutive days in Wistar rats.Therefore, the MABGmscg dressing is considered safe for use as a hemostatic gauze. [ABSTRACT FROM AUTHOR]

AbstractCCl4 causes oxidative injury, fatty degeneration, fibrosis of the liver, renal failure, and even hepatocellular and renal carcinoma. Certain substances have the potential to neutralize the harmful effects of CCl4, so it will lead to numerous beneficial effects. Melatonin (MEL) is a powerful antioxidant that regulates circadian rhythm and has beneficial effects on organism; tryptophan (TRP) is its precursor necessary for the synthesis of MEL. The aim of the current study was to determine whether MEL and TRP, have protective effects during subchronic application of CCl4 to the liver and kidneys. Results suggest that CCl4 led to decrease of total proteins, albumins, globulins, erythrocytes, hemoglobin, and hematocrit; and increase of creatinine, AST, ALT values, and leukocytes. MEL and TRP both showing protective effects on regulation of serum proteins, albumins, globulins, A/G, AST, ALT, and creatinine levels. TRP had been shown to have potential in regulation of disbalanced hematological parameters caused by CCl4. TRP had beneficial effects on hepatocyte morphology in term of beaded chromatin and preserved cell morphology. Overall, oral supplementation of TRP had better protective effects on liver/kidneys compared to MEL. [ABSTRACT FROM AUTHOR]

7-Methylxanthine (7-MX, CAS No. 552-62-5, purity 99.46%) is the first orally administered drug candidate, which showed anti-myopic activity in different pre-clinical studies. In the present study, we investigated the in-vivo genotoxic and mutagenic toxicity of 7-MX in Wistar rats using comet/single-cell gel electrophoresis, chromosomal aberration and micronucleus assays after oral administration. For the single-dose study (72 h), two doses of 7-MX 300 and 2000 mg/kg body weight were selected. For a repeated dose 28 d study, three doses (250, 500, and 1000 mg/kg) of 7-MX were selected. The doses were administered via oral gavage in the suspension form. Blood and major vital organs such as bone marrow, lung and liver were used to perform comet/single cell gel electrophoresis, chromosomal aberration, and micronucleus assays. The in-vitro Ames test was performed on TA98 and TA100 strains. In the chromosomal aberration study, a non-significant increase in deformities such as stickiness, ring chromosome, and endoreduplication was observed in bone marrow cells of 7-MX treated groups. These chromosomal alterations were observed upon treatment with doses of 2000 mg/kg single dose for 72 h and 1000 mg/kg repeated dose for 28 d. At a dose of 500 mg/kg, DNA damage in terms of tail length, tail moment, % tail DNA and the olive tail moment was also found to be non-significant in 7-MX treated groups. The Ames test showed the non-mutagenic nature of 7-MX in both strains of TA98 and TA100 of Salmonella typhimurium with or without metabolic activation. Thus, the present work is interesting in view of the non- genotoxicity and non-mutagenicity of repeated doses of 7-MX. [ABSTRACT FROM AUTHOR]

The effects of high-fat-associated kidney damage in humans are not completely elucidated. Animal experiments are essential to understanding the mechanisms underlying human diseases. This systematic review aimed to compile evidence of the role of a high-fat diet during the development of renal lipotoxicity and fibrosis of Wistar rats to understand whether this is a satisfactory model for the study of high fat-induced kidney damage. We conducted systematic searches in PUBMED, EMBASE, Lilacs, and Web of Science databases from inception until May 2021. The risk of bias was assessed using SYRCLE toll. Two reviewers independently screened abstracts and reviewed full-text articles. A total of 11 studies were included. The damage varied depending on the age and sex of the animals, time of protocol, and amount of fat in the diet. In conclusion, the Wistar rat is an adequate animal model to assess the effects of a high-fat diet on the kidneys. A high-fat diet may promote kidney damage in Wistar rats. Wistar rat is efficient as an animal model to study high-fat-induced kidney damage. The effect of the diet depends on the fat amount, consumption time, and animal age. [ABSTRACT FROM AUTHOR]

Fenpyroximate (FEN) is an acaricide that inhibits the complex I of the mitochondrial respiratory chain in mites. Data concerning mammalian toxicity of this acaricide are limited; thus the aim of this work was to explore FEN toxicity on Wistar rats, particularly on cardiac, pulmonary, and splenic tissues and in bone marrow cells. rats were treated orally with FEN at 1, 2, 4, and 8 mg/Kg bw for 28 days. After treatment, we analyzed lipid profile, oxidative stress and DNA damage in rat tissues. FEN exposure increased creatinine phosphokinase (CPK) and lactate dehydrogenase (LDH) activities, elevated total cholesterol (T-CHOL), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) concentrations, while decreasing high-density lipoprotein cholesterol (HDL-C). It inhibited acetylcholinesterase (AChE) activity, enhanced lipid peroxidation, protein oxidation, and modulated antioxidant enzymes activities (superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase). Comet assay indicated that FEN induced a dose-dependent DNA damage, contrasting with the micronucleus test showing no micronuclei formation. Nonetheless, FEN exhibited cytotoxicity to bone marrow cells, as evidenced by a reduction in the number of immature erythrocytes among total cells. FEN appears to carry out its genotoxic and cytotoxic activities most likely through an indirect pathway that involves oxidative stress. [ABSTRACT FROM AUTHOR]

The brain is built up during pregnancy. How it functions afterwards depends on how the expectant mother's diet nourishes it. Walnuts contain significant quantities of polyunsaturated fatty acids (PUFAs) and bioactive phytochemicals, which enhance brain health and function even with advancing age. This study examined the effects of a walnut-enriched diet (WED) on corticohippocampal histoarchitecture and gene expression in rat offspring. Twenty-eight female adult Wistar rats (n= 7) averaging about 185 g in weight were used for this study. After mating, pregnant dams were split randomly into four groups: A (standard rat chow/control), B (WED from GD 0 – PND 21), C (WED from GD 0 – PND 1), D (WED from PND 1 – PND 21). Offspring of dams were sacrificed at adolescence (PND 35), with brain tissues of interest harvested for subsequent analyses. We observed no significant correlates in litter size, body, and brain weights across the experimental groups. Histomorphology revealed no distortion in cellular layering and delineation of cells in the PFC and dentate gyrus of both control and WED groups. Nissl staining intensity was enhanced in the offspring of dams exposed to WED versus the control, indicating improved proteostasis. Upregulated mRNA expression of DNMT3a, H2Ax, OPA1, and BDNF was observed in cortical and hippocampal tissues of WEDexposed offspring compared with the control group. A diet enriched with African walnuts during early development induced changes predictive of cognitive improvements and enhanced stress-response signalling, plasticity, and neural resilience in rat offspring. [ABSTRACT FROM AUTHOR]

Fenpyroximate (FEN) is an acaricide that inhibits the complex I of the mitochondrial respiratory chain. The aim of this work was to explore the hepatotoxic and nephrotoxic effects of FEN on Wistar rats. The study involved five groups: a control group and four groups treated with FEN at 1, 2, 4, and 8 mg/Kg bw for 28 consecutive days. Histological examination and biochemical analysis of hepatic and renal biomarkers were performed. The malondialdehyde (MDA), protein carbonyl levels, and antioxidant enzymes activities were measured. Comet assay was conducted to explore FEN genotoxicity. FEN induced a disturbance of the hepatic and renal functions as evidenced by an increase in AST, ALT, ALP, creatinine, and uric acid levels and histopathological modifications in the two examined tissues. FEN increased hepatic and renal lipid peroxidation and protein oxidation. The activities of liver and kidney SOD, CAT, GPX, and GST are increased significantly in FEN-treated rats at doses of 2 and 4 mg/kg bw. However, with the dose of 8 mg/kg bw of FEN, these activities are decreased. Moreover, FEN increased DNA damage in a dose-dependent manner. FEN was hepatotoxic and nephrotoxic very likely through induction of oxidative stress. [ABSTRACT FROM AUTHOR]

Mesua ferrea Linn. is used traditionally in India and South East Asian countries as an antiseptic, antidote and a brain tonic. Recent pharmacological studies on the plant have highlighted M. ferrea to be a rich source of secondary metabolites, with proven therapeutic applications. Since the toxicity of a plant following repeated exposure is of higher clinical significance, the present investigation was conducted to establish the subacute toxicity profile of the ethanolic extract of Mesua ferrea flowers (MFE). The study was conducted in accordance with the OECD Guideline 407, wherein MFE was administered orally to groups of male and female rats (n = 5/group/sex) at the doses of 100, 500 and 1000 mg/kg, over a period of 28 days. Repeated administration of MFE had no adverse effect on the growth rate and hematological parameters of the animals. There were no changes in the biochemical parameters, except for a slight decrease in the CHOL (total cholesterol) levels, and an increase in the levels of AST (aspartate aminotransferase) and ALT (alanine aminotransferase), at the highest dose. The latter corroborated with the histopathological findings exhibiting mild lymphocytic infiltration and hepatocyte degeneration observed in the liver tissues of both sexes. According to the study, the no-observed-adverse-effect level (NOAEL) of M. ferrea in the 28-day repeated dose toxicity study in rats was 500 mg/kg. Though the overall effects of the extract at the highest dose did not translate into any serious complications, its effect on hepatic function needs to be established over a longer period of study. [ABSTRACT FROM AUTHOR]

The present study investigated the hepatoprotective effects of seabuckthorn (Hippophae rhamnoides) leaf-extract (SLE) supplementation in lead acetate-intoxicated Wistar rats. Adult male Wistar rats (n = 35) were divided into five equal groups as per completely randomized design. Group I was kept as a control, group II received 250 ppm lead acetate in drinking water, and group III received SLE at 100 mg/kg body weight per os. Animals in group IV and group V received lead acetate at 250 ppm in drinking water for the first 45 days. Additionally, group IV received SLE at 100 mg/kg body weight per os throughout the experiment, whereas group V received SLE at 100 mg/kg body weight per os during the last 15 days of the trial. Blood samples were collected on day zero and at the 45th and 60th day to study the liver function enzymes. Lead exposure caused increase in aspartate aminotransferase (AST), alanine aminotransferase (ALT), acid phosphatase (ACP), and alkaline phosphatase (ALP) activity, and liver weight, and hepatic oxidative stress in lead acetate-intoxicated groups (groups II, IV, and V) as compared to group I. SLE on simultaneous supplementation with lead acetate (group IV) exerted a protective effect against lead toxicity. SLE supplemented after the establishment of lead acetate-toxicity (group V) also reduced the AST, ALT, and ALP activity and hepatic oxidative stress, indicating its ameliorative effect. SLE supplementation at 100 mg/kg body weight per os protects against hepatic damage caused by 250 ppm lead acetate in the drinking water of Wistar rats. [ABSTRACT FROM AUTHOR]

Xanthine oxidase (XO) is accountable for the uric acid synthesis in the body and is considered as a prominent therapeutic target in urate lowering treatment. Eugenol is a natural compound commonly found in clove, cinnamon, etc. and has various biological activities. This study was designed to examine the anti-hyperuricemic effect of eugenol by in vitro and in vivo studies. Potassium oxonate (PO) was used to induce hyperuricemia in Wistar rats. Different doses of eugenol (1.25, 2.5, and 5 mg/kg bwt orally) were used for the treatment and various biological function markers (renal, hepatic, and hematological) were analyzed. The IC50 value obtained for eugenol was 3.51 ± 0.002 μM. The kinetic studies revealed that the eugenol exhibited a mixed type of inhibition. Abnormality in the levels of various biological function markers was observed in the PO treated rats. Upon the eugenol treatment, those biological function markers were retained near to its normal values. The study proved the anti-hyperuricemic potential of eugenol against the PO induced hyperuricemia model. [ABSTRACT FROM AUTHOR]

The consumption of non-nutritive sweeteners has increased in the last decades. However, there are doubts about its consumption and its impact on body mass and metabolic alterations. For this reason, this study investigates the effects of the consumption of nutritive and non-nutritive sweeteners on body mass in different life stages of male and female Wistar rats: Childhood, adolescence, young adult, adulthood, and aged. For this purpose, 8 groups of male and female rats were used (10 per group/gender): sucrose 10%, glucose 14%, fructose 7%, acesulfame K 0.05%, aspartame:acesulfame mixture 1.55%, sucralose 0.017%, saccharin 0.033%, and a control group. Only in aged male rats (504 days) there were significant differences in body mass. In both genders, there were differences in food, drink, and energy intake along all life stage. It is concluded that non-nutritive sweeteners when consumed together with a balanced diet did not cause a greater body mass gain. [ABSTRACT FROM AUTHOR]

Lagenaria siceraria (Cucurbitaceae) is traditionally known to be used for the treatment of diabetes, ulcer, jaundice, cardiovascular disease, hemorrhoids, and colitis. This study involves evaluation of acute and subacute toxicity of methanolic extract of L. siceraria fruit (MELSF) in rats for assessment of its safety profile. For acute oral toxicity, single dose (2000 mg/kg body weight) of extract was administered in female Wister rats while in the subacute study the extract was given at doses of 250, 500, and 1000 mg/kg orally over 28 d in male and female rats. No evidence of toxicity was observed in animals when acutely exposed to MELSF, implying that the LD50 is higher than 2000 mg/kg body weight. Further, repeated administration of the extract for 28 d did not alter any hematological and biochemical parameters and no significant changes were observed in organ and body weight of control and treated groups. Histopathological assessment was normal in kidney and liver. Thus, the present investigation shows that MELSF, at dosage levels up to 1000 mg/kg, is nontoxic and can show protection of some body tissues when administered for 28 d and therefore can be considered safe. This study supports the application of L. siceraria in traditional medicine. [ABSTRACT FROM AUTHOR]

Colistin-induced nephrotoxicity (CIN) occurs in up to 60% of patients, and this has restricted its clinical use. In view of its efficacy amidst the rising challenge of infections caused by multidrug-resistant bacteria, current studies are focusing on ways to ameliorate colistin-induced nephrotoxicity. This study investigated treatment-time differences in colistin-induced nephrotoxicity in Wistar rats. A dose of 600,000 IU/Kg/day of colistimethate sodium (CMS) was administered to male Wistar rats to induce nephrotoxicity; the rats tolerated the higher dose for the treatment duration with higher mean values of serum creatinine, urea, and malondialdehyde compared to the group that received 450,000 IU/Kg/day CMS (p ≤ 0.05). Four groups (n = 8/group) of rats received intraperitoneal (i.p.) injections of 600,000 IU/Kg/day CMS each at four equally spaced circadian times (00:00, 06:00, 12:00, and 18:00 h) to determine the time of administration with least renal toxicity. Biomarkers of oxidative stress and renal toxicity were measured and kidney histology studied after the treatments. The results showed a 24-h pattern in nephrotoxicity from CIN, and that treatment during the activity time period (dark phase) caused lowest CIN. Histological findings supported this finding, with photomicrographs consistently showing more pronounced features of CIN in the groups treated during time frame that coincided with the rest phase in rats (12:00 and 18:00). [ABSTRACT FROM AUTHOR]

An ideal food-chemical combination that will promote insulin resistance and its consequent development of pancreatic beta-cell dysfunction may open a new vista for Type 2 diabetes (T2D) research. Thus, we investigated the modulatory effects of a high-fructose diet (FRC) combined with glyphosate (GP). Male albino Wistar rats were randomly divided into five groups of eight/group and received distilled water, FRC, GP, and their combinations orally for eight consecutive weeks. We assessed the changes in fasting blood glucose levels (FBGLs), biochemical indices, oxidative stress parameters, and organ histopathology. From the results obtained, FBGLs and serum insulin levels were increased in the FRC-GP (2.3–3.1 and 1.9–2.2 folds) treated rats compared with the control baseline group. Also, the FRC-GP high dose increased FBGLs (1.9 folds), insulin (1.4 folds), triglycerides (1.5 folds), and uric acid (2 folds) levels compared with the FRC group. Malondialdehyde levels increased in the pancreas (54% and 78%) and liver (31.3% and 56.6%) of the FRC-GP treated rats. The FRC-GP treatments reduced serum high-density lipoprotein (57%), total protein (47%), and antioxidant parameters (non-enzymatic and enzymatic, 1.6–1.9 folds) respectively in the treated animals. The weight of the pancreas relative to the body increased (2–3 folds) while we observed mild inflammation and vascular congestion in vital organs in the treated rats. Overall, these results demonstrate the potential of FRC-GP-diet to induce conditions of rats T2D. Also, this novel finding suggests a cost-effective GP as an alternative in this model type and provides further insight into understanding FRC-GP interactions. [ABSTRACT FROM AUTHOR]

The objective of the present study was to evaluate the sexual behavior of male rats kept under constant laboratory conditions for one entire year. A total of 213 sexually-inexperienced, male Wistar rats were maintained in controlled environmental conditions from birth. Depending the month in which they reached the age 3-month-old, the male rats were divided into 12 groups, one for each month of the year, and their sexual behavior was evaluated. Records of their sexual behavior were made from 09:00 to 11:00 hrs am. The following parameters were recorded: mount (latency and number), intromission (latency and number), ejaculation latency, and intromission rate. During the months of March, June, July and September, the rats showed lower mount and intromission latencies than in January, February, April, May and October-to-December. Similarly, in March, June, July and August they had higher copulatory efficiency than in January, February, April and December. Results suggest that male rats exposed to controlled environmental conditions could have endogenous mechanisms that regulate sexual behavior but are independent of seasonal environmental signals. The annual variability in the sexual behavior of male rats maintained under constant laboratory conditions should be considered when planning research and experiments. [ABSTRACT FROM AUTHOR]

Despite the dangers associated with the increased use of prescription opioid drugs, limited researches have addressed the specific effects of prescription opioids on the brain. The objective of this study was to assess the effects of codeine medication on the prefrontal cortex and cerebellum of Wistar rats. The drugs, ArchilinTM with codeine syrup and Dihydrocodeine 30 mg tablets were used for this study. Thirty (30) male Wistar rats were divided into 5 groups labeled A, B, C, D, and E, n = 6. Group A served as control and was given normal saline, group B was treated with 1 mg/kg bodyweight dihydrocodeine, group C was treated with 2 mg/kg bodyweight dihydrocodeine, group D was treated with 2 ml/kg bodyweight ArchilinTM with codeine syrup and group E was treated with 4 ml/kg bodyweight ArchilinTM with codeine syrup. Drugs were administered orally and daily for 21 days. At the end of the treatment period, animals were sacrificed via intraperitoneal injection of ketamine hydrochloride, brains were perfused with phosphate-buffered saline and formal saline before harvested and postfixed in 10% neutral buffered formalin. Sections of the prefrontal cortex and cerebellum were obtained and processed for immunohistochemical studies using GFAP stain. Results from the study suggested that prolonged administration of codeine medication produced an inflammatory reaction in the prefrontal cortex and cerebellum of treatment groups. This neuroinflammatory reaction is an indicator of a pathologic process that could lead to neuronal degeneration, glial degeneration, and altered physiologic process in the prefrontal cortex and cerebellum. [ABSTRACT FROM AUTHOR]

The toxic effects of ACR monomer include carcinogenesis, cellular genotoxic, and neurotoxicity. In this study, we examined the effect of acrylamide on biochemical and hematologic parameters in Wistar rats and explored the renal and hepatic function of these animals through a complementary anatomopathologic study. For it, thirty female Wistar rats aged 4 weeks and weighing 100 ± 10 g were housed six animals per cage and divided as follows: two groups were exposed for 2 months to drinking water containing 5 mg (Group 2) or 10 mg acrylamide (Group 3); one group of 12 rats received the median lethal dose of acrylamide by gavage (Group 4); and the control group (Group 1) received pure water. The results clearly showed that acrylamide affects various biochemical parameters, such as creatinine, urea, and serum globulin levels and the lipid balance, which are directly related to renal and hepatic dysfunction and disruption of the hematologic system. In addition, the data revealed changes in the complete blood count (CBC); significant increases in the number of leukocytes (9.95 ± 1.44 and 10.44 ± 1.21) and lymphocytes (6.11 ± 0.48 and 6.33 ± 0.76) in Groups 3 and 4, respectively; and decreases in total protein (88.95 ± 6.36), albumin (37.65 ± 1.65) and α-1 globulin levels (24.84 ± 2.10) in Group 3. The anatomopathologic study confirmed liver damage in the animals administered an acrylamide containing diet compared with those in the control group. The present study confirmed the effects of acrylamide on different hematologic, biochemical and immunologic parameters, with a specific focus on the liver and kidney, and on the induction of neurotoxic disorders. The results showed that oral exposure to acrylamide via drinking water or gavage induces kidney damage, hepatocellular insufficiency and chronic liver disease, resulting in primary immunodeficiency and activation of the immune system following the possible expression of certain immunoreaction genes. [ABSTRACT FROM AUTHOR]

A trypsin inhibitor isolated from tamarind seed (TTI) has satietogenic effects in animals, increasing the cholecystokinin (CCK) in eutrophy and reducing leptin in obesity. We purified TTI (pTTI), characterised, and observed its effect upon CCK and leptin in obese Wistar rats. By HPLC, and after amplification of resolution, two protein fractions were observed: Fr1 and Fr2, with average mass of [M + 14H]+ = 19,594,690 Da and [M + 13H]+ = 19,578,266 Da, respectively. The protein fractions showed 54 and 53 amino acid residues with the same sequence. pTTI presented resistance to temperature and pH variations; IC50 was 2.7 × 10−10 mol.L−1 and Ki was 2.9 × 10−11 mol.L−1. The 2-DE revealed spots with isoelectric points between pH 5 and 6, and one near pH 8. pTTI action on leptin decrease was confirmed. We conclude that pTTI is a Kunitz trypsin inhibitor with possible biotechnological health-related application. [ABSTRACT FROM AUTHOR]

This study investigated changes in kidney, liver and erythrocyte of male rats after exposure to ground water samples collected in the studied areas and treated water sample. Results reveal high levels of heavy metals in water from studied areas and a concomitant accumulation of metals in liver, kidney and blood of rats. Heavy metal contaminated underground water (HMCUW) caused a significant increase in levels of malondialdehyde (MDA) and decreased activities of superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST), including glutathione (GSH) levels. Principal component analysis implicated geogenic and anthropogenic factors for underground water contamination by heavy metals in the areas. However, activities of gamma-glutamyl transferase (γ-GT), 51 nucleotidase (51NT), glutathione peroxidase (GSH-Px), and myeloperoxidase (MPO) significantly increased in kidney, liver and erythrocytes of rats compared with control group (p < 0.001). We observed significant (p < 0.001) increase in serum electrolytes, urea and creatinine levels compared to control. Heavy metals in HMCUW are above ambient levels and possess significant decrease in triiodothyronine (T3) and thyroxine (T4) levels. Histology revealed alterations in architecture of the kidney and liver. Prolonged exposure to HMCUW could induce oxidative damage in kidney, liver and erythrocyte which could elicit liver and kidney dysfunctions. [ABSTRACT FROM AUTHOR]

We used automated sperm morphology analysis to investigate rat sperm morphometry and morphology in Sprague-Dawley and Wistar rats in three research centers to develop normal baseline values for sperm morphometry and to quantify the percentage of morphologically normal sperm in healthy rats. The participating centers were IRSN in Paris, France (Sprague-Dawley rats), University of the Western Cape, South Africa (Wistar rats) and Stellenbosch University (Wistar rats), South Africa. All three centers used identical sperm isolation techniques from the cauda epididymis, the same staining protocols, identical computer-aided sperm morphometry analysis (CASMA) software and microscopes with similar optics. With CASMA, fully automated analysis of the different parts of stained sperm, e.g., head, acrosome, mid-piece, can be performed, many sperm morphometric features can be measured accurately and eventually normal sperm morphology can be defined. We found that it is possible to distinguish sperm morphometric characteristics of Sprague-Dawley and Wistar rats. We also developed cut-off values for evaluating the percentage normal sperm in these two rat strains using the automatic analysis mode. Normal sperm morphology varied between 67 and 74% by contrast with previous findings of > 90%. [ABSTRACT FROM AUTHOR]

This study aimed to analyze the effects of caloric restriction on aged femoral articular cartilage of Wistar rats. Three groups of eight animals each were considered: young (YC) and old (OC) control groups fed with a normal diet and old caloric restriction group (OCR) composed of 18-month-old animals fed with a 31% less caloric diet from 6-months of age. Articular cartilage was studied through morphometry and immunohistochemistry. Body mass was 12% less in the OCR group than in the OC group. The articular cartilage from OC rats show thinner medial condyles, fewer chondrocytes, smaller chondrocytes nuclear volume and, in both condyles, a predominance of collagen type II and less collagen density compared to both YC and OCR groups (p < .001). In contrast, OCR articular cartilage show thicker medial condyles, larger chondrocytes nuclear volume and increased collagen density compared to OC group (p < 0.001). We concluded that caloric restriction minimizes the effects of aging on medial condyles of the femoral articular cartilage. [ABSTRACT FROM PUBLISHER]

Low-level lasers are widespread in regenerative medicine, but the molecular mechanisms involved in their biological effects are not fully understood, particularly those on DNA stability. Therefore, this study aimed to investigate mRNA expression of genes related to DNA genomic stability in skin and skeletal muscle tissue fromWistarrats exposed to low-level red and infrared lasers. For this,TP53(Tumor Protein 53) andATM(Ataxia Telangiectasia Mutated gene) mRNA expressions were evaluated by real-time quantitative PCR (RT-qPCR) technique 24 hours after low-level red and infrared laser exposure. Our data showed that relativeTP53mRNA expression was not significantly altered in both tissues exposed to lasers. ForATM, relative mRNA expression in skin tissue was not significantly altered, but in muscle tissue, laser exposure increased relativeATMmRNA expression. Low-level red and infrared laser radiations alterATMmRNA expression related to DNA stability in skeletal muscle tissue. [ABSTRACT FROM AUTHOR]

Natural products play a dominant role in the development of novel drug leads for the treatment and prevention of diseases. Toxicity is an expression of being poisonous, indicating the state of adverse effects led by the interaction between toxicants and cells. This interaction may vary depending on the chemical properties of the toxicants and the cell membrane. Hence, evaluation of toxic properties of a substance is crucial when considering for public health protection. Protease inhibitors (PIs) are low molecular mass proteins that are ubiquitous in nature. They are natural antagonists of protease, which are present in all life forms. The present study aims to determine the toxicity of purified PI from the fruits of Solanum aculeatissimum using an acute and subchronic oral toxicity test in animal models. No significant changes in the enzymes level were observed. No adverse changes were noticed in the experimental animal treated with purified PI. [ABSTRACT FROM AUTHOR]

Background:Among various types of polyunsaturated fatty acid (PUFA), omega-3 fatty acids play a crucial role in development and function of the brain. This study was undertaken to investigate the possible neuroprotective efficacy of omega-3 fatty acid on lead-induced neurotoxicity in rats. Material and methods:The experiment was carried out on 32 male Wistar rats divided into four groups. The first group (control) was treated with distilled water and second group with lead acetate at the doses of 3 mg/kg b.wt. (body weight)/oral, whereas third and fourth groups were simultaneously treated with lead acetate (3 mg/kg b.wt.) plus omega-3 fatty acid (300 mg/kg b.wt./oral) and lead acetate (3 mg/kg b.wt.) plus vitamin E (100 mg/kg b.wt./oral), respectively, for a period of 90 days. Their biochemical and histopathological investigations have been carried out. Results:The level of lead was markedly elevated in brain (4.71-fold) and blood (5.65-fold), also increased levels of ROS, GSH, LPO with concomitant reduction in the activities of delta-ALAD, CAT, SOD, and GPx. In addition, lead-induced brain damage was indicated by histopathological changes. Omega-3 fatty acid resulted in marked improvement in most of the biochemical parameters as well as histopathological changes in rats. The results obtained were compared with vitamin E as the standard antioxidant agents. Discussion:Omega-3 fatty acid significantly (P < 0.05) decreased the effect of lead-induced brain damage as well as biochemical changes similar to that of standard drug, vitamin E. So, our result suggested that omega-3 fatty acid may play a protective role in lead-induced neurotoxicity and associated human health risk. [ABSTRACT FROM AUTHOR]

Background: Combined therapy with epidermal growth factor (EGF) and growth hormone-releasing peptide 6 (GHRP-6) in stroke models has accumulated evidence of neuroprotective effects from several studies, but needs further support before clinical translation. Comparing EGF + GHRP-6 to hypothermia, a gold neuroprotection standard, may contribute to this purpose. Objectives: The aims of this study were to compare the neuroprotective effects of a combined therapy based on EGF + GHRP-6 with hypothermia in animal models of (a) global ischemia representing myocardial infarction and (b) focal brain ischemia representing ischemic stroke. Methods: (a) Global ischemia was induced in Mongolian gerbils by a 15-min occlusion of both carotid arteries, followed by reperfusion. (b) Focal brain ischemia was achieved by intracerebral injection of endothelin 1 in Wistar rats. In each experiment, three ischemic treatment groups – vehicle, EGF + GHRP-6, and hypothermia – were compared to each other and to a sham-operated control group. End points were survival, neurological scores, and infarct volume. Results: (a) In global ischemia, neurological score at 48–72 h, infarct volume, and neuronal density of hippocampal CA1 zone in gerbils treated with EGF + GHRP-6 were similar to the hypothermia-treated group. (b) In focal ischemia, the neurologic score and infarct volume of rats receiving EGF + GHRP-6 were also similar to animals in the hypothermia group. Discussion: With hypothermia being a good standard neuroprotectant reference, these results provide additional proof of principle for EGF and GHRP-6 co-administration as a potentially neuroprotective stroke therapy. [ABSTRACT FROM AUTHOR]

Objective: To analyze the apoptosis of cortical and hippocampal neurons in newborn following the intramuscular administration of betamethasone in pregnant Wistar rats. Methods: Betamethasone or placebo was administered to 10 pregnant rats. Subsequently, 98 newborns were analyzed in three different groups: therapeutic dose (TD, 20 mg/kg), triple therapeutic dose (3TD, 60 mg/kg), and nine times TD (9TD, 180 mg/kg). Forty-four newborns were injected with placebo (control subjects – CTR). Neuronal apoptosis was measured by immunofluorescence using the TUNEL assay. The one-way analysis of variance, Tukey–Kramer (parametric) test and Kruskal–Wallis (non-parametric) test were used for statistical analysis. Results: The CA1 area of the hippocampus of TD and 3TD groups showed significant differences from that of the CTR group (p < 0.001). Compared to the CTR group, there was increased neuronal apoptosis in the dentate gyrus (DG) of animals in TD and 3TD groups (p < 0.0001). There were no significant differences in CA2 and CA3 regions as well as in amygdala and cortex. Conclusion: Prenatal administration of betamethasone leads to significant changes in neuronal apoptosis in CA1 and DG regions. [ABSTRACT FROM PUBLISHER]

Purpose: The radioprotectors currently available are generally poorly tolerated in human beings; thus, their use has been restricted due to their side effects and their limited clinical tolerance. In a search for fewerand/or without side effects agents, the radioprotective effects of partial body hyperthermia (PBH) were tested on Wistar rats of both sexes at different ages.Materials and methods: PBH (43 °C, 1 h) was carried out by immersion of each animal’s lower parts and legs in a thermostatically controlled water bath 20 h prior to irradiation with a lethal single exposure dose of 9 Gy of gamma irradiation. Irradiated PBH pretreated animals were monitored for 30 days post-irradiation and survival percentages were calculated.Results: The data obtained provide evidence that PBH treatment prolonged the irradiated rats’ lifespans and the mortality rates varied significantly with animal age and sex. In addition, PBH treatment significantly enhanced bone marrow recovery of irradiated rats of both genders.Conclusions: Partial body hyperthermia prior to radiation proved to have beneficial effects on gamma irradiated rats. [ABSTRACT FROM PUBLISHER]

Lopinavir (LPV)-loaded poly-&varepsilon;-caprolactone (PCL) nanoparticles (NPs) were prepared by emulsion solvent evaporation technique. Effects of various critical factors in preparation of loaded NPs were investigated. Box-Behnken design (BBD) was employed to optimize particle size and entrapment efficiency (EE) of loaded NPs. Optimized LPV NPs exhibited nanometeric size (195.3 nm) with high EE (93.9%). In vitro drug release study showed bi-phasic sustained release behavior of LPV from NPs. Pharmacokinetic study results in male Wistar rats indicated an increase in oral bioavailability of LPV by 4-folds after incorporation into PCL NPs. From tissue distribution studies, significant accumulation of loaded NPs in tissues like liver and spleen indicated possible involvement of lymphatic route in absorption of NPs. Mechanistic studies using rat everted gut sac model revealed endocytosis as a principal mechanism of NPs uptake. In vitro rat microsomal metabolism studies demonstrated noticeable advantage of LPV NPs by affording metabolic protection to LPV. These studies indicate usefulness of PCL NPs in enhancing oral bioavailability and improving pharmacokinetic profile of LPV. [ABSTRACT FROM AUTHOR]

Thousands of chemicals are being used recently in our new high tech foods like ready to eat Japanese, Chinese, packaged and tinned foods. Most food additives act as either preservatives or flavor enhancers like monosodium glutamate (MSG), a sodium salt of glutamic acid. The present study investigated the effect of intraperitoneally administered MSG on cortex of the kidneys of adult albino Wistar rats and compared with control group. The histomorphometry done by calibrating with ocular micrometer on kidney tissue of control and experimental group revealed a significant difference in glomeruli with increase in length, size of bowman's capsule with an increase in bowman's space. The size of renal tubules could not be compared as the cells of these tubules in experimental group were disintegrated and distorted. In the experimental group (rats treated with 4 mg MSG/g body weight), the cortex of the kidneys developed variable pathological changes, which were patchy in distribution with intervening normal areas. There was distortion of renal cytoarchitecture. Many glomeruli (66.4%) showed hypercellularity, i.e., cellular proliferation of mesangial or endothelial cells and infiltration of inflammatory cells. The capillary membrane showed thickening as was evident on PAS stain. Since MSG, as a food additive, was found to be toxic on various organs of the body by various researchers, it should perhaps be stopped from being used as a food additive. This may be a suggestion which needs validation in human studies. [ABSTRACT FROM AUTHOR]

Magnetic iron oxide nanoparticles with appropriate surface chemistry have been widely used with potential new applications in biomedical industry. Therefore, the aim of this study was to assess the size-, dose-, and time-dependent effects, after acute oral exposure to iron oxide-30 NP (Fe2O3-30), on various biochemical enzyme activities of clinical significances in a female Wistar rat model. Rats were exposed to three different doses (500, 1,000, and 2,000 mg/kg) of Fe2O3-30 and Fe2O3-Bulk along with control. Fe2O3-30 had no effect on growth, behavior, and nutritional performance of animals. Fe2O3-30 caused significant inhibition of acetylcholinestrase in red blood cells as well as in brains of treated rats. Further, more than 50% inhibition of total, Na+-K+, Mg2+, and Ca2+-ATPases activities, as observed in brains of exposed female rats, may be the result of disturbances in cellular physiology and the iono-regulatory process. Activation of the hepatotoxicity marker enzymes, aspartate aminotransferase and alanine aminotransferase, was recorded in serum and liver, whereas inhibition was observed in kidney. Similarly, enhancement of lactate dehydrogenase activity was observed in serum and liver; however, a decrease in enzyme levels was observed in kidneys of Fe2O3-30-treated rats. On the other hand, Fe2O3-Bulk did not depict any significant changes in these biochemical parameters, and alterations were near to control. Therefore, this study suggests that exposure to nanosize particles at acute doses may cause adverse changes in animal biochemical profiles. The use of the rat model signifies the correlation with the human system. [ABSTRACT FROM AUTHOR]

Pyrimethamine is a dihydrofolate reductase inhibitor which has been used for therapy and prophylaxis of parasitic diseases. A simple method is described for the quantification of pyrimethamine in plasma by liquid chromatography. Chromatographic separation was achieved on a reversed phase C18 column (250 mm × 4.6 mm, particle size 5μm, Vydac®) using mobile phase containing 0.05 M sodium phosphate buffer (pH 2): methanol (50:50, v/v). Pyrimethamine and internal standard carbamazepine were measured using UV detection at 212 nm. Retention times for drug and internal standard from rat plasma samples were found to be 8.7 and 13.5 min, respectively. The lower limit of quantification was 13 ng/ml. Mean recoveries from plasma were 96–98%. Intra- and inter-day precision (%RSD) was 4.2 and 7.4%, respectively whereas intra- and inter-day accuracy (%RSD) was 5.6 and 6.3%, respectively. Short-term stability studies at room temperature and freeze-thaw conditions indicated absence of degradation in pyrimethamine. The method was successfully applied to the pharmacokinetic study of pyrimethamine after oral administration of 1.25 mg/kg dose in healthy Wister rats. All pharmacokinetic parameters derived were found to be statistically significant (p < 0.0001). The method was sensitive, specific, precise and suitable for pharmacokinetic studies of pyrimethamine in rats. [ABSTRACT FROM AUTHOR]

Context: Chromolaena odorata (L.) R.M.King & H.Rob. (Asteraceae) or Siam weed has long been used to stop bleeding in Thailand and many countries. Only the aqueous leaf extract was investigated in in vivo and there have been conflicting results of in vitro hemostatic mechanisms of this plant. Objective: The most appropriate C. odorata leaf extract that promoted the highest hemostatic activity and the hemostatic mechanisms of these plant extracts will be investigated. Materials and methods: The lyophilized aqueous leaf extract and alcoholic (50, 70, and 95% ethanol) extracts from the fresh and dried leaves were investigated both in vivo and in vitro. The bleeding time in male Wistar rats was measured to investigate the hemostatic effect. The hemostatic mechanisms were tested using in vitro platelet aggregation and blood coagulation tests in sheep plasma. Results: All extracts displayed significantly reducing bleeding time (<2.5 min) in rats but did not induce platelet aggregation or blood clotting in the in vitro study. The in vitro blood clotting times of all extracts were > 0.6 min. Ethanol extract (70%) from the dried leaves proved to be the extract producing the highest hemostatic activity in vivo with the bleeding time of 1.85 min. Discussion and conclusion: The in vivo study with rats confirmed the significant ability of this plant extract to stop bleeding. However, the sufficient amount of calcium and active compounds which are aggregating and clotting agents to enhance blood coagulation and platelet aggregation in in vitro tests should be further studied. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the protective action of licorice in diabetic nephropathy in male rats. Diabetes was induced in male Wistar rats by using streptozotocin (60 mg/kg body weight). Daily oral ingestion (1 g/kg body weight) of licorice extract for 60 days after the onset of diabetes reversed the adverse effect of diabetes on rats. Licorice extract alleviated blood glucose levels, restored renal function, and attenuated body-weight loss. In addition, licorice extract modulated the adverse effect of diabetes on renal malondialdehyde, glutathione, superoxide dismutase, and catalase activity. Further, licorice extract restored the total antioxidant capacity of diabetic rat kidneys. The biochemical analyses were reinforced by histologic investigations, where focal segmental glomerulosclerosis, tubular damage, and hyperemic kidney were the histologic changes seen in diabetic, but not in treated, rats. In conclusion, the biochemical analysis and the histologic investigations of diabetic rat kidneys treated with licorice extract revealed that licorice may have a potential therapeutic effect for diabetes due to its antioxidant and -hyperglycemic properties. [ABSTRACT FROM AUTHOR]

Acetone leaf extracts of Combretaceae species Combretum imberbe Wawra, Combretum nelsonii Duemmer, Combretum albopunctatum Suesseng, and Terminalia sericea Burch ex DC and a mixture of asiatic acid and arjunolic acid isolated from C. nelsonii were tested for antifungal activity against Candida albicans, Cryptococcus neoformans, Microsporum canis, and Sporothrix schenckii on wounds of immunocompromised Wistar rats. The therapeutic agents were selected based on low MIC values ranging 0.02–2.5 mg/mL and low toxicity (LC50) ranging 75.7–168.6 μg/mL. Seven circular, full-thickness wounds were made on the back skin of 24 Wistar rats, under general anesthetic and using an aseptic technique. Rats were infected with different fungal pathogens in groups of six. The treatments were administered topically using 20% concentrations of each extract in aqueous cream. Amphotericin B was used as positive control. Erythema, exudate, crust formation, swelling, and ulceration were used to determine the wound healing process. Throughout the experiment, body temperature, measured using a subcutaneous probe, and weight of the rats were found to be within normal ranges. Epithelial closure in all rats occurred by 17 days. There was no significant difference in contraction of the lesion areas treated with different extracts. The variability in erythema at each lesion in rats infected with different fungal pathogens differed with treatments; the lesion without treatment took a longer time to heal in all cases. Exudate formation was observed until day 12 in rats infected with C. albicans and day 8 in rats infected with C. neoformans. In lesions infected with M. canis and S. schenckii, exudate formation was observed until day 10. The treated group presented a rigid, dark, and thick crust formation after day 3 until day 15. During histopathological evaluations, scant fungi were noted in all the wounds, indicating that infection had occurred but had generally cleared. The antifungal potential of crude extracts of selected plants and a mixture of asiatic acid and arjunolic acid on the wounds of immunocompromised rats was confirmed. The extracts of these plants may possibly be further developed into drugs for topical treatment of fungally infected wounds. [ABSTRACT FROM AUTHOR]

Wistar rats maintained in cages with running wheels and submitted to a skeleton photoperiod or to a light - dark cycle were tested in the Morris water maze. Half of the animals were exposed to the task during their active phase while the other half was exposed during their inactive phase. The effect of the experience in the water maze, a strong arousing event, on the rhythm of wheel-running activity was evaluated. In the first experiment, a group of animals submitted to a skeleton photoperiod was trained every day in the reference memory version of the task. The novel experience in the water maze had a strong phase-dependent masking effect: it produced an intense post-training bout of activity in the animals tested during their inactive phase. Another experiment was run using single working memory sessions in the water maze and with animals submitted to a light - dark cycle. The circadian rhythm of locomotor activity was evaluated on undisturbed days and compared with testing days. The experience in the water maze produced a significant increase in variability of activity onset during both circadian phases. Taken together, the data suggest that there is a modulating effect of the arousing experience in the pool on the overt circadian rhythm of locomotor activity. [ABSTRACT FROM AUTHOR]

In recent years, the exposure of humans to phthalate esters through environmental contamination has increased. One among them is di-ethyl phthalate (DEP), which is used as a plastisizer for cellulose ester plastic films and sheets, solid rocket propellants, molded and extruded articles, as a component in insecticide sprays and various other substances, as well as in industrial applications. Release into the environment occurs primarily as a result of production and manufacturing of DEP and during the use and disposal of products containing DEP. Therefore, a study was undertaken to evaluate gender-specific toxicity of DEP in Wistar rats. Rats of both sexes, weighing 125-130 g, were administered 50 ppm (w/v) DEP in water ad libitum for a period of 180 days and were given normal diet. Control animals received normal diet and water ad libitum. During the treatment, rats were weighed every week and water consumption per day was measured. After the completion of treatment, liver weight : body weight-1 ratio, liver weight, body weight-1, liver and serum enzymes, and other biochemical parameters of liver and serum were assessed. It was observed that there was no significant change in body weight-1, liver weight, liver weight : body weight-1 ratio, and water consumption in both sexes. There were significant increases in liver acid phosphatase (ACP) activity and kidney glutathione levels, and nonsignificant changes in liver alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), succinate dehydrogenase (SDH), and lactate dehydrogenase (LDH) activities in DEP-treated male rats, whereas in DEP-treated female rats the liver showed significant decrease in ALP and SDH and nonsignificant changes in AST, ALT, and LDH activities. Serum ACP and LDH levels in DEP-treated male rats were significantly decreased, and in the case of DEP-treated female rats, only serum LDH levels were significantly decreased. There was no significant change in serum ALP, AST, and SDH levels in DEP-treated male and female rats as compared to control rats. Histology of the livers of both male and female rats showed loss of hepatic architecture, degenerative changes in hepatocytes, and vacuolation in hepatocytes in both the centrilobular and periportal areas. It can be concluded from this study that prolonged exposure to DEP at 50 ppm levels can be harmful to animals and humans. This is evident from the present study as certain significant changes in enzyme activities in the liver, serum, and histological alterations in liver were observed. [ABSTRACT FROM AUTHOR]

Activity of Carica papaya Linn, (commonly known as paw-paw) seed extract in liver physiology of albino (Wistar) rats was studied. The MeOH extract of C papaya seeds were Soxhlet extracted. Tolerated doses of C papaya were estimated in acute toxicity studies and administered orally, single or repeated doses, for 30 days to adult male rats weighing between 190 and 200 g, which were divided into four groups of five rats per group. Group 1 received 10 mg/kg; group 2 received 50 mg/kg; group 3 received 200 mg/kg; group 4 received normal saline (1 ml/rat) as control. Twenty-four hours after treatments, the animals of all groups were sacrificed and blood samples collected by heart puncture into centrifugal tubes. The blood samples were allowed to coagulate before centrifuged at 400 rpm at 4°C for 15 min to separate the serum for enzyme assays. A portion of liver was cut off and fixed in 10% normal saline. The result showed that C. papaya seed extract treatments caused elevation of rat serum levels of acid phosphatase (ACP), alkaline phosphatase (ALP), and aspartate amino transferase (AST). Also revealed was mild to severe metaplasia of hepatocytes in a dose-related manner as well as proliferation of Kupfer cells and hepatic cells cirrhosis. These biochemical and pathological changes indicated liver cell damage and malfunction. These results, therefore, suggest that seeds of C. papaya should be used in herbal medicine with care to avoid toxicity. [ABSTRACT FROM AUTHOR]

The effects of food on biological rhythms may influence the findings of chronopharmacological studies. The present study evaluated the influence of a restricted food access during the rest (light) span of nocturnally active Wistar rats on the 24 h time organization of biological functions in terms of the circadian rhythms of temperature (T), heart rate (HR), and locomotor activity (LA) in preparation for subsequent studies aimed at evaluating the influence of timed food access on the pharmacokinetics and pharmacodynamics of medications. Ten‐wk‐old male Wistar rats were housed under controlled 12:12 h light:dark (LD) environmental conditions. Food and water were available ad libitum , excepted during a 3 wk period of restriction. Radiotelemetry transmitters were implanted to record daily rhythms in T, HR, and LA. The study lasted 7 wk and began after a 21‐d recovery span following surgery. Control baseline data were collected during the first wk (W1). The second span of 3 wk duration (W2 to W4) consisted of the restricted feeding regimen (only 3 h access to food between 11:00 and 14:00 h daily) during the L (rest span) under 12:12 h LD conditions. The third period of 3 wk duration (W5 to W7) consisted of the recovery span with ad libitium normal feeding. Weight loss in the amount of 5% of baseline was observed during W1 with stabilization of body weight thereafter during the remaining 2 wk of food restriction. The 3 h restricted food access during the L rest span induced a partial loss of circadian rhythmicity and the emergence of 12 h rhythms in T, HR, and LA. Return to ad libitum feeding conditions restored circadian rhythmicity in the manner evidenced during the baseline control span. Moreover, the MESORS and amplitudes of the T, HR, and LA 24 h patterns were significantly attenuated during food restriction ( p [ABSTRACT FROM AUTHOR]

Ferulic acid is the major active constituent in many natural Chinese medicinal herbs. The metabolism of ferulic acid has been investigated using solid-phase extraction and HPLC-DAD methods that were established to separate and analyze the metabolites in urine, feces and bile. Three metabolites, identified by enzymatic hydrolysis, HPLC-DAD, HPLC-MS and MS/MS, are all glucuronic acid conjugates of ferulic acid. Ferulic acid conjugated with one glucuronic acid at different positions produces M1 and M3. Ferulic acid conjugated with two glucuronic acids produces M2, which is the main metabolite. A metabolic pathway is proposed. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate cisplatin-induced ototoxicity and the protective effects of tiopronin. Twenty-four adult Wistar rats served as subjects and were divided into three groups. Eight rats receiving only saline (group A) were used as controls. Eight rats received cisplatin (2 mg/kg) injections (group B) and eight rats received cisplatin and tiopronin (300 mg/kg) (group C) for 8 consecutive days. Both ears of all animals were tested by DPOAE before treatment and on the 4th and 9th days. Seventy-two hours after the final recording session, all animals were killed, and the left cochleas were prepared for electron microscopy and analysed. DPOAE responses were significantly reduced in group B compared to controls (p < 0.05). When tiopronin was added, DPOAE responses were significantly increased compared to those obtained with the administration of cisplatin alone (p < 0.05). The cochleogram showed that tiopronin had a significant protective effect in the basal half and in the lower half of the middle turn. We conclude that tiopronin, a drug effective in protecting against cisplatin nephrotoxicity, is also effective in protecting against cisplatin ototoxicity. [ABSTRACT FROM AUTHOR]

N-acetylcysteine (NAC), a synthetic aminothiol, possesses antioxidative and cytoprotective properties. The present study evaluates the effect of NAC supplementation on arsenic-induced depletion in vivo of carbohydrates. Arsenic (as sodium arsenite) treatment (i.p.) of male Wistar rats (120-140 g b.w.) at a dose of 5.55 mg/kg body weight (35% of LD50) per day for a period of 30 days produced a significant decrease in blood glucose level (hypoglycemia) and a fall in liver glycogen and pyruvic acid contents. The free amino acid nitrogen content of liver increased while that of kidney decreased after arsenic treatment. Arsenic also enhanced the liver lactate dehydrogenase activity whereas glucose 6-phosphatase activity in both liver and kidney decreased significantly following arsenic treatment. Transaminase activities in liver and kidney were not significantly altered except the glutamate- pyruvate transaminase activity that was reduced in kidney after arsenic treatment. Oral administration of NAC (163.2 mg/kg/day) for last 7 days of treatment prevented the arsenic-induced hypoglycemia and glycogenolytic effects to an appreciable extent. There was also recovery of liver pyruvic acid as well as liver and kidney free amino acid nitrogen content after NAC supplementation. Arsenic-induced alteration of glucose 6-phosphatase activity in both liver and kidney was also counteracted by NAC. It is suggested that carbohydrate depletion in vivo due to exposure to arsenic can be counteracted by NAC supplementation. [ABSTRACT FROM AUTHOR]

The influence of information load on ethanol and water intake of altered magnetic background was studied in initially ethanol-aversive Wistar rats. A paradigm of free choice between 10% of ethanol solution and water was applied. Daily exposure to weak disturbances of ambient magnetic field (MF, up to 210 µT) caused by various ferromagnetic objects under conditions of free behavior (zero level of information load) did not alter rats' ethanol/water intake over 2 months. Cognitive activity on the background of natural MF (38 µT) caused an increase of ethanol intake in 34.8% of rats, which were mainly poor learners. This activity on the background of altered MF (up to 280 µT) modulated by magnets provoked an increase of stable ethanol addiction in all rats, independent of individual peculiarities and learning success. A possible role of the endogenous opioid system in mediating MF-induced development of alcohol addiction is discussed. [ABSTRACT FROM AUTHOR]