Pathological Effects of Graded Doses of Aflatoxin B1 on the Development of Testes in Juvenile White Leghorn Males

Abstract Current experiment was planned to investigate the deleterious effects of the graded dose of aflatoxin B1 (AFB1) on White Leghorn Male Birds. For this purpose, 100 birds of 8 week age were divided into 4 equal groups and reared on feed contaminated with different doses of AFB1 for 10 weeks. Group A was kept as a control group and was fed with normal toxin free diet, group B, C, and D were offered feed containing 100 ppb, 200 ppb, and 400 ppb of AFB1 respectively. The birds were euthanized at the 4th and 10th week of the experiment. Clinical signs, behavioral changes, absolute and relative organ weight of testes, sperm motility were measured. Cellular immune response was observed through CCA, P-HAP, and antibody response against SRBC. Results showed a dose-dependent decline in the immune response of birds with the increase in the level of AFB1 in the feed. A significant decrease in the serum levels of testosterone, prolactin, and LH was observed. Grossly, testicular size and volume were reduced in ABF1 fed birds while histological examination showed mild to moderate and severe necrosis of testicular parenchyma, with partial to complete arrest of spermatogenesis. Very few spermatozoa were found in group C while they were almost absent in group D which was offered a diet containing 400 ppb AFB1. The above-mentioned results showed that AFB1 had severe toxic effects on the reproductive and immunological parameters of WLH birds in a dose-dependent manner.

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Hepatoprotective Potential of Elsholtzia densa Against Acute and Chronic Models of Liver Damage in Wistar Rats

Drug Research ◽

10.1055/s-0044-102094 ◽

2018 ◽

Vol 68 (10) ◽

pp. 567-575 ◽

Cited By ~ 1

Author(s):

Ovais Zargar ◽

Rohina Bashir ◽

Showkat Ganie ◽

Akbar Masood ◽

Mohammad Zargar ◽

...

Keyword(s):

Wistar Rats ◽

Liver Toxicity ◽

Methanolic Extract ◽

Serum Levels ◽

Hepatoprotective Activity ◽

Control Group ◽

Dependent Manner ◽

Protein Levels ◽

Chronic Models ◽

Dose Dependent

AbstractThe aim of the present study was to evaluate the hepatoprotective activity of methanolic extract of Elsholtzia densa against experimentally induced acute (CCl4) and chronic (paracetamol) liver injury in albino wistar rats. Activity was measured by monitoring the serum levels of ALT, ALP AST and LDH, total protein levels, bilirubin and albumin. The results of the CCl4 and paracetamol-induced liver toxicity experiments showed that the rats treated with the methanolic extract of Elsholtzia densa exhibited a significant decrease in biochemical parameters as well as the proteins, which were all elevated in the CCl4 and paracetamol group. The extract at a concentration of 300 mg/kg body wt. showed a significant decline (P≤0.05) in the levels of AST, ALT, ALP and LDH to 69.50±2.23IU/L, 60.01±2.25IU/L,46.20±2.24 IU/L and 150.21±5.68IU/L in CCl4 injected animals and 51.12±2.20 IU/L,49.15±3.25 IU/L, 44.12±2.56 IU/L and 125.15±4.45 IU/L in paracetamol-treated animals when compared to the control group. The activities of tissue antioxidants GSH, GPx, GR, GST and CAT was significantly (P≤0.05) restored in dose dependent manner in animals treated with extracts as with acute and chronic hepatotoxic models. The current study confirmed the hepatoprotective effect of methanolic extract of Elsholtzia densa against the model hepatotoxicant CCl4 and paracetamol.

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Changes in growth rate and thyroid- and sex-hormones blood levels in rats under sub-chronic lithium treatment

Human & Experimental Toxicology ◽

10.1191/0960327106ht620oa ◽

2006 ◽

Vol 25 (5) ◽

pp. 243-250 ◽

Cited By ~ 9

Author(s):

M S Allagui ◽

N Hfaiedh ◽

C Vincent ◽

F Guermazi ◽

J-C Murat ◽

...

Keyword(s):

Growth Rate ◽

Lithium Treatment ◽

Lithium Carbonate ◽

Serum Levels ◽

Antagonistic Effect ◽

Blood Levels ◽

Vaginal Mucosa ◽

Dependent Manner ◽

Serum Concentrations ◽

Dose Dependent

Lithium therapy, mainly used in curing some psychiatric diseases, is responsible for numerous undesirable side effects. The present study is a contribution to the understanding of the pathophysiological mechanisms underlying lithium toxicity. Male and female mature rats were divided into three batches and fed commercial pellets: one batch was the control and the second and third batches were given 2 g (Li1) and 4 g (Li2) of lithium carbonate/kg of food/day, respectively. After 7, 14, 21 and 28 days, serum levels of free tri-iodothyronine (FT3), thyroxine (FT4), testosterone and estradiol were measured. Attention was also paid to growth rate and a histological examination of testes or vaginal mucosa was carried out. In treated rats, a dose-dependent loss of appetite and a decrease in growth rate were observed, together with symptoms of polydypsia, polyuria and diarrhea. Lithium serum concentrations increased from 0.44 mM (day 7) to 1.34 mM (day 28) in Li1 rats and from 0.66 to 1.45 mM (day 14) in Li2 rats. Li2 treatment induced a high mortality after 14 days, reaching 50-60% in female and male animals. From these data, the LD50 (14 days Li2 chronic treatment) was calculated to be about 0.3 g/day per kilogram of animal, leading to Li serum concentrations of about 1.4 mM. A significant decrease of FT3 and FT4 was observed in treated rats. This effect appeared immediately for the highest dose and was more pronounced for FT3, resulting in an increase of the FT4/FT3 ratio. In males, testosterone decreased and spermatogenesis was stopped. Conversely, in females, estradiol increased in a dose-dependent manner as the animals were blocked in the diestrus phase at day 28. This finding supports a possible antagonistic effect of lithium on the estradiol receptors.

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Effect of Synchronous Versus Sequential Regimens on the Pharmacokinetics and Biodistribution of Regorafenib with Irradiation

Pharmaceutics ◽

10.3390/pharmaceutics13030386 ◽

2021 ◽

Vol 13 (3) ◽

pp. 386

Author(s):

Tung-Hu Tsai ◽

Yu-Jen Chen ◽

Li-Ying Wang ◽

Chen-Hsi Hsieh

Keyword(s):

Stereotactic Body Radiation Therapy ◽

In Vivo Studies ◽

Control Group ◽

High Dose ◽

Dependent Manner ◽

Hep G2 ◽

Time Curve ◽

Dose Dependent

This study was performed to evaluate the interaction between conventional or high-dose radiotherapy (RT) and the pharmacokinetics (PK) of regorafenib in concurrent or sequential regimens for the treatment of hepatocellular carcinoma. Concurrent and sequential in vitro and in vivo studies of irradiation and regorafenib were designed. The interactions of RT and regorafenib in vitro were examined in the human hepatoma Huh-7, HA22T and Hep G2 cell lines. The RT–PK phenomenon and biodistribution of regorafenib under RT were confirmed in a free-moving rat model. Regorafenib inhibited the viability of Huh-7 cells in a dose-dependent manner. Apoptosis in Huh-7 cells was enhanced by RT followed by regorafenib treatment. In the concurrent regimen, RT decreased the area under the concentration versus time curve (AUC)regorafenib by 74% (p = 0.001) in the RT2 Gy × 3 fraction (f’x) group and by 69% (p = 0.001) in the RT9 Gy × 3 f’x group. The AUCregorafenib was increased by 182.8% (p = 0.011) in the sequential RT2Gy × 1 f’x group and by 213.2% (p = 0.016) in the sequential RT9Gy × 1 f’x group. Both concurrent regimens, RT2Gy × 3 f’x and RT9Gy × 3 f’x, clearly decreased the biodistribution of regorafenib in the heart, liver, lung, spleen and kidneys, compared to the control (regorafenib × 3 d) group. The concurrent regimens, both RT2Gy × 3 f’x and RT9Gy × 3 f’x, significantly decreased the biodistribution of regorafenib, compared with the control group. The PK of regorafenib can be modulated both by off-target irradiation and stereotactic body radiation therapy (SBRT).

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Effect of lemon peel flavonoids on anti-fatigue and anti-oxidation capacities of exhaustive exercise mice

Applied Biological Chemistry ◽

10.1186/s13765-020-00573-3 ◽

2020 ◽

Vol 63 (1) ◽

Author(s):

Guili Bao ◽

Yinglong Zhang ◽

Xiaoguang Yang

Keyword(s):

Skeletal Muscle ◽

Superoxide Dismutase ◽

Manganese Superoxide Dismutase ◽

Fatty Acid Content ◽

Hepatic Tissue ◽

Control Group ◽

Dependent Manner ◽

Lemon Peel ◽

Tnf Α ◽

Dose Dependent

AbstractIn this study, lemon peel flavonoids (LPF) were administered to investigate its effect on the anti-fatigue and antioxidant capacity of mice that undergo exercise until exhaustion. LPF (88.36 min in LPFH group mice) significantly increased the exhaustion swimming time compare to the untreated mice (40.36 min), increased the liver glycogen and free fatty acid content in mice and reduce lactic acid and BUN content in a dose-dependent manner. As the concentration of lemon peel flavonoids increased, the serum creatine kinase, aspartate aminotransferase, and alanine aminotransferase levels of mice gradually decreased. LPF increases superoxide dismutase (SOD) and catalase (CAT) levels in mice and reduces malondialdehyde levels in a dose-dependent manner. And LPF raises hepatic tissue SOD, CAT activities and reduces skeletal muscle tissue iNOS, TNF-α levels of mice compared to the control group. LPF also enhanced the expression of copper/zinc-superoxide dismutase (Cu/Zn-SOD), manganese-superoxide dismutase (Mn-SOD), and CAT mRNA in mouse liver tissue. LPF also enhanced the expression of alanine/serine/cysteine/threonine transporter 1 (ASCT1) mRNA and attenuate the expression of syncytin-1, inducible nitric oxide synthase (iNOS), and tumor necrosis factor (TNF)-α in mouse skeletal muscle. According to high-performance liquid chromatography (HPLC) analysis, it was found that LPF contains flavonoids such as rutin, astragalin, isomangiferin, naringin, and quercetin. Our experimental data show that LPF has good anti-fatigue effects and anti-oxidation ability. In summary, LPF has high prospects to be developed and added to nutritional supplements.

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Toxicopathological effects of lambda-cyhalothrin in female rabbits (Oryctolagus cuniculus)

Human & Experimental Toxicology ◽

10.1177/0960327110376550 ◽

2010 ◽

Vol 30 (7) ◽

pp. 591-602 ◽

Cited By ~ 11

Author(s):

Abdul Basir ◽

Ahrar Khan ◽

Riaz Mustafa ◽

Muhammad Zargham Khan ◽

Farzana Rizvi ◽

...

Keyword(s):

Blood Cell ◽

Oryctolagus Cuniculus ◽

Hemoglobin Concentration ◽

Control Group ◽

Mean Corpuscular Hemoglobin ◽

Dependent Manner ◽

Cell Counts ◽

Lambda Cyhalothrin ◽

Group A ◽

Dose Dependent

The aim of this study was to investigate effects of lambda-cyhalothrin (LCT) on clinical, hematological, biochemical and pathological alterations in rabbits (Oryctolagus cuniculus). New Zealand white female rabbits (n = 24) of 4-5 months age having 997.92 ± 32.83 g weight were divided into four equal groups. Group A (control) received normal saline intraperitoneally (ip). Animals in groups B, C and D were treated with LCT 1.0, 4.0 and 8.0 mg/kg bw ip. Each group received seven consecutive doses at an interval of 48 hours. Blood and serum samples were collected at an interval of 96 hours. Blood analysis revealed a significant (p < 0.05) decrease in red blood cell and white blood cell counts, hemoglobin concentration and lymphocytes, while mean corpuscular hemoglobin concentration, mean corpuscular volume, neutrophils, monocytes and eosinophils were increased. Serum biochemical analysis revealed significant (p < 0.05) decrease in serum total proteins and serum albumin, while an increase was seen in serum alanine aminotransferase and aspartate aminotransferase activities compared with the control group. Serum globulin values varied non-significantly in all treatment groups as compared to control group. A dose-dependent increase in the incidence of micronucleated polychromatic erythrocyte was observed. All gross and histopathological lesions observed in LCT-treated rabbits were dose-dependent. Liver of the treated rabbits exhibited extensive perihepatitis, hyperplasia of bile duct, necrosis, hemorrhages and congestion. In lungs, there were hemorrhages, thickened alveolar walls, congestion, emphysema, collapsed alveoli and accumulation of extensive inflammatory cells. Kidneys were congested and hemorrhagic whereas renal parenchyma and stroma were normal. Microscopically, heart showed congestion of blood vessels and nuclear pyknosis, myodegeneration. It was concluded from the study that LCT produced toxicopathological alterations in rabbits in a dose-dependent manner. On the basis of the results, it can be suggested that overdosing of LCT be avoided while treating animals for ectoparasites.

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Aflatoxin B1 and Clinoptilolite in Feed for Laying Hens: Effects on Egg Quality, Mycotoxin Residues in Livers, and Hepatic Mixed-Function Oxygenase Activities

Journal of Food Protection ◽

10.4315/0362-028x-66.5.860 ◽

2003 ◽

Vol 66 (5) ◽

pp. 860-865 ◽

Cited By ~ 27

Author(s):

L. RIZZI ◽

M. SIMIOLI ◽

P. RONCADA ◽

A. ZAGHINI

Keyword(s):

Cytochrome P450 ◽

Lipid Metabolism ◽

Aflatoxin B1 ◽

Laying Hens ◽

Egg Quality ◽

Diet Group ◽

Control Group ◽

Complete Diet ◽

Group 2 ◽

Mixed Function Oxygenase

Ninety-six laying hens were allocated to four groups administered different diets (group 0-0 received a complete diet, group 0-AF received a diet supplemented with 2.5 ppm of aflatoxin B1 [AFB1], group 2-0 received a diet supplemented with 2% clinoptilolite [CPL], and group 2-AF received a diet supplemented with 2% CPL and 2.5 ppm of AFB1) for 4 weeks to evaluate the effect of AFB1 and/or CPL on egg quality and the ability of CPL to interact with the oral administration of AFB1. The possible effects of AFB1 on cytochrome P450–dependent hepatic mixed-function oxygenase (MFO) activities were also evaluated. Mycotoxin reduced yolk weight, while CPL influenced albumen percentage relative to that of eggs laid by chickens in group 0-AF. Eggs laid by chickens in groups 0-AF and 2-AF had stronger shells and weighed less than the eggs of other groups. The eggs of treated groups were lighter in color than those of the control group (P < 0.01), and the tendency to yellowness in eggs was increased by CPL, probably through the affinity of red pigments for adsorbents and a consequent prevalence of yellow tonality. Color parameters might be connected with AFB1's interference with lipid metabolism and pigment deposition. The livers of hens in groups 0-AF and 2-AF showed very low mycotoxin concentrations that were significantly different (P < 0.01). The highest levels observed were those in the livers of the hens receiving the diet supplemented with the mycotoxin alone. AFB1 did not exert any significant effects on the hepatic MFO activities examined.

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Hepatoprotective effects of Sapium sebiferum in paracetamol-induced liver injury

Bangladesh Journal of Pharmacology ◽

10.3329/bjp.v10i2.22576 ◽

2015 ◽

Vol 10 (2) ◽

pp. 393 ◽

Cited By ~ 3

Author(s):

Liaqat Hussain ◽

Muhammad Sajid Hamid Akash ◽

Madeha Tahir ◽

Kanwal Rehman

Keyword(s):

Liver Injury ◽

Serum Levels ◽

Therapeutic Effects ◽

Sapium Sebiferum ◽

Dependent Manner ◽

Protective Effects ◽

Drug Induced ◽

Standard Drug ◽

Hepatoprotective Effects ◽

Dose Dependent

Sapium sebiferum leaves were used to determine its hepatoprotective effects against paracetamol-induced hepatotoxicity in mice. A dose dependent study was conducted using two different doses (200 mg/kg and 400 mg/kg) of the extract of S. sebiferum against toxic effects of paracetamol (500 mg/kg) in experimental animal model. Silymarin (50 mg/kg) was used as standard drug to compare therapeutic effects of S. sebiferum with control and paracetamol-treated groups. Paracetamol significantly increased the serum levels of liver enzyme markers like alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, and direct bilirubin. The extract showed protective effects by normalizing the liver enzymes markers in a dose dependent manner. Histopathological results confirmed the hepatoprotective effects of leaves of S. sebiferum. We conclude that leaves of S. sebiferum have strong hepatoprotective effects against paracetamol-induced liver injury and can be used in liver injuries caused by drug-induced toxicity.

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Follicle-stimulating hormone stimulates inhibin in the serum of male monkeys (Macaca mulatta)

Acta Endocrinologica ◽

10.1530/acta.0.1220096 ◽

1990 ◽

Vol 122 (1) ◽

pp. 96-100 ◽

Cited By ~ 7

Author(s):

Ulrich Fingscheidt ◽

Gerhard F. Weinbauer ◽

Shafiq A. Khan ◽

Eberhard Nieschlag

Keyword(s):

Macaca Mulatta ◽

Half Life ◽

Rhesus Monkeys ◽

Follicle Stimulating Hormone ◽

Serum Levels ◽

Lag Time ◽

Dependent Manner ◽

Control Serum ◽

Dose Dependent ◽

Stimulating Hormone

Abstract. Three adult rhesus monkeys were injected intramuscularly with human FSH at doses of 2, 10 or 25 IU/kg in a cross-over design with 3-week intervals between injections. On each occasion a fourth animal received saline only as control. Serum levels of exogenous FSH were monitored by a fluoroimmunoassay specific for human FSH. Serum inhibin was measured by a heterologous radioimmunoassay. Each FSH injection was followed by a rise in serum inhibin in a dose-dependent manner. The half-life of human FSH in rhesus monkeys ranged from 25.1 to 32.9 h with no significant differences between doses. The rise of inhibin occurred with a lag time of 53.3 to 61.9 h after injection of FSH, independent of the dose administered. These findings support the concept that inhibin secretion in male primates is stimulated by FSH.

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GENETIC ASPECTS OF PREGNANCY MISCARRIAGE

Likarska sprava ◽

10.31640/jvd.5-6.2019(8) ◽

2019 ◽

pp. 71-76

Author(s):

K. M. Lisova ◽

I. V. Kalinovska ◽

O. M. Yuzko

Keyword(s):

Pregnant Women ◽

Molecular Genetic ◽

Clinical Signs ◽

Clinical Manifestations ◽

Control Group ◽

Molecular Genetic Study ◽

Immunological Parameters ◽

Fetoplacental Complex ◽

Maternal Genotype ◽

A1166c Polymorphism

Pregnancy miscarriage is a consequence of many factors. The aim of the study was to analyze the effect of miscarriage gene on embryometric, ultrasound, hormonal, immunological parameters in pregnant women, and to evaluate its prognostic value. The main group includes 31 pregnant women who had clinical signs of miscarriage in current or previous pregnancy. The control group consists of 32 healthy pregnant women whose clinical-paraclinical parameters served as a control to compare the data of the pregnancy survey of the main surveillance group. A general clinical examination and a special obstetrical examination (complaints, anamnesis, general medical examination, obstetric examination), biochemical studies (determination of hormones of the fetoplacental complex in blood serum of pregnant women), ultrasound, immunological studies, histological studies of the placenta, molecular genetic study A1166C polymorphism of the AGTR1 gene were made. In the course of the research, the genetic determinism of miscarriage was discovered. The polymorphism of the A1166C of the AGTR1 gene was considered as a prognostic marker of miscarriage in early gestational term and preeclampsia in the second half of pregnancy. A reliable marker of abortion was the maternal genotype 1166AC for the genome AGTR1. The risk of occurrence of clinical manifestations of abortion increased five times. At simultaneous influence of all prognostic factors the risk of abortion increased 6,25 times. Detection of genetic markers of pregnancy miscarriage will allow early correction of this pathology and prevent perinatal loss.

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ATI-2341 Trifluoroacetic Acid (TFA) Promotes Menstrual Blood-Derived Mesenchymal Stem Cell Recruitment and Enhances Uterine Repair Through Gi Pathway in Asherman’s Syndrome

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2022.2936 ◽

2022 ◽

Vol 12 (3) ◽

pp. 506-513

Author(s):

Ying Lv ◽

Liyan Ye ◽

Xiujuan Zheng

Keyword(s):

Menstrual Blood ◽

Control Group ◽

Dependent Manner ◽

Asherman’S Syndrome ◽

Expression Levels ◽

Endometrial Cells ◽

Injury Model ◽

Recruitment Effect ◽

Dose Dependent

This study aimed to explore the role of ATI-2341 in Asherman’s syndrome and its impact on menstrual blood-derived mesenchymal stem cells (MenSCs). Following establishment of endometrial injury model, MenSCs were extracted from rats and cultured. They were treated with ATI-2341 TFA at different concentrations (10 ng/mL, 50 ng/mL, 100 ng/mL) and MenSCs treated without ATI-2341 TFA were taken as controls. Flow cytometry was conducted to detect the cell cycle. MTT was carried out to evaluate proliferation of endometrial cells. The expression levels of MMP-9, TIMP-1, CK, and VIM were determined with staining used to reflect morphology of endometrium. Administration with ATI-2341 TFA resulted in decreased expression of MMP-9 and increased expression of TIMP-1 in a dose-dependent manner. Of note, the increase of ATI-2341 TFA concentration was accompanied with elevated cell proliferation rate, increased number of glands in the endometrium, and decreased fibrosis area. As treated with 100 ng/mL ATI-2341 TFA, the cells exhibited more glands than that under other concentrations with uniformly arranged glands and lowest expression levels of CK and VIM, control group had plenty of blue-stained collagen fibers in the intima and least amount of glands. ATI-2341 TFA 100 ng/mL induced endometrial epithelial recruitment effect on MenSCs and promoted endometrial repair more significantly than Gi-3 pathway agonists. Collectively, ATI-2341 TFA enhances MenSC recruitment and facilitates endometrial epithelial cells proliferation and the repair of uterine damage in Asherman’s syndrome through Gi pathway. These findings provide a\ novel insight into the MenSC-based treatment against Asherman’s syndrome and deserve further investigation.

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