scholarly journals Sub-Chronic Toxicity Study of Hydroethanolic Leaf Extract of Telfairia Occidentalis Hook. F. (Cucurbitaceae) in Rats

Author(s):  
Abidemi J. Akindele ◽  
Joy A. Oladimeji-Salami ◽  
Ramon A. Oyetola ◽  
Daniel D. Osiagwu

Background: The leaf of Telfairia occidentalis Hook f. (Cucurbitaceae) is consumed in different parts of Nigeria because of the numerous nutritional and medicinal attributes ascribed to it. The sub-chronic toxicity of the hydroethanolic leaf extract of Telfairia occidentalis (TO) was investigated in this study. Methods: Rats in different groups were separately administered 80, 400 and 2000 mg/kg TO p.o. for 60 days. Animals were sacrificed and blood samples collected for haematological and biochemical analysis. Vital organs were harvested and evaluated for in vivo antioxidants and histopathological changes. Results: Results showed no significant changes in the weight of vital organs except in respect of the testes of the group treated with 2000 mg/kg extract which showed a significant (p<0.05) reduction in weight compared to the control group. There was a significant (p<0.01) increase in sperm motility and count of the group administered 80 mg/kg extract and a significant (p<0.001) reduction was observed at 2000 mg/kg. There were significant increases in the level of Hb and PCV at 80 and 2000 mg/kg of the extract. In respect of liver function parameters, a significant decrease in AST and ALT levels at doses of 400 and 2000 mg/kg relative to control was observed. A significant reduction (p<0.05) in the level of total cholesterol (400 mg/kg) and increase (p<0.05) in level of HDL (80-2000 mg/kg) compared to control was observed. There was also significant (p<0.05) increase in the level of MDA and significant (p<0.05) decrease in SOD level in the testes at 2000 mg/kg. Histopathological assessment of the testes revealed abnormality at this dose. These effects were reversed after 30 days of cessation of administration of TO. Conclusions: The findings showed that the hydroethanolic leaf extract of Telfairia occidentalis is relatively non-toxic on acute and sub-chronic exposure, with potential to elicit anti-anaemic effect, reduce the risk of atherosclerosis and cardiovascular disease, and enhance antioxidant status in the brain and liver. Although possibly beneficial at low dose, the extract could be harmful to the testes on prolonged oral exposure at high dose.

2017 ◽  
Vol 7 (1) ◽  
pp. 171
Author(s):  
Hamid Reza Adeli Bhroz ◽  
Kazem Parivar ◽  
Iraj Amiri ◽  
Nasim Hayati Roodbari

Background and Aim: Thyroid is one of the endocrine glands, (T3 and T4) play a significant role in the development of prenatal brain and the following stages. The study aimed to evaluate the effect of hypothyroidism on the amount of expression of NT4, NT3, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in brain of one-day rat neonates with hypothyroidism.Materials and Methods: In total, 25 mature mice of Albino NMRI race were selected after mating, divided into three group, control, as well as low-dose and high-dose intervention groups. Samples of the control group received pure water during pregnancy, whereas subjects of the intervention group with low and high doses of the medication were administered with 20 mg and 100 mg methimazole powder (dissolved in 100 cc water), respectively. After child delivery, blood samples were obtained from mother mice to determine the level of T3 and T4 in blood serum. Following that, the brain of one-day mice were removed by surgery and assessed to determine the amount of expression of NT4, NT3, NGF and BDNF using the complete kit of RT-PCR.Results: Levels of T4 and T3 in the control group were 28 ug/dl and 1.59 ug/dl, respectively. In the low-dose intervention group, the amounts of the mentioned hormones were 8 ug/dl and 0.85 ug/dl, significantly, indicating a significant reduction in the expression of NT4, NT3, NGF and BDNF genes, compared to the control group. Moreover, T4 and T3 were 6 ug/dl and 0.79 ug/dl in the high-dose group, respectively, conveying a significant decrease in the expression of NT4, NT3, NGF and BDNF genes, compared to the control group (P<0.05).


2004 ◽  
Vol 287 (6) ◽  
pp. H2746-H2753 ◽  
Author(s):  
Gentian Kristo ◽  
Yukihiro Yoshimura ◽  
Byron J. Keith ◽  
Randy M. Stevens ◽  
Salik A. Jahania ◽  
...  

The purpose of this study was to determine whether the adenosine A1/A2a receptor agonist AMP-579 induces acute and delayed preconditioning against in vivo myocardial stunning. Regional stunning was produced by 15 min of coronary artery occlusion and 3 h of reperfusion (RP) in anesthetized open-chest pigs. In acute protection studies, animals were pretreated with saline, low-dose AMP-579 (15 μg/kg iv bolus 10 min before ischemia), or high-dose AMP-579 (50 μg/kg iv at 14 μg/kg bolus + 1.2 μg·kg−1·min−1 for 30 min before coronary occlusion). The delayed preconditioning effects of AMP-579 were evaluated 24 h after administration of saline vehicle or high-dose AMP-579 (50 μg/kg iv). Load-insensitive contractility was assessed by measuring regional preload recruitable stroke work (PRSW) and PRSW area. Acute preconditioning with AMP-579 dose dependently improved regional PRSW: 129 ± 5 and 100 ± 2% in high- and low-dose AMP-579 groups, respectively, and 78 ± 5% in the control group at 3 h of RP. Administration of the adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (0.7 mg/kg) blocked the acute protective effect of high-dose AMP-579, indicating that these effects are mediated through A1 receptor activation. Delayed preconditioning with AMP-579 significantly increased recovery of PRSW area: 64 ± 5 vs. 33 ± 5% in control at 3 h of RP. In isolated perfused rat heart studies, kinetics of the onset and washout of AMP-579 A1 and A2a receptor-mediated effects were distinct compared with those of other adenosine receptor agonists. The unique nature of the adenosine agonist AMP-579 may play a role in its ability to induce delayed preconditioning against in vivo myocardial stunning.


Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 947
Author(s):  
Hend Mohamed Anwar ◽  
Gehan S. Georgy ◽  
Sherin Ramadan Hamad ◽  
Wafaa K. Badr ◽  
Mohamed A. El Raey ◽  
...  

Aluminum (Al) is an omnipresent mineral element in the environment. The brain is a central target of Al toxicity, being highly susceptible to oxidative damage. Therefore, recognition of drugs or natural products that guard against Al-mediated neuronal cell death is a powerful strategy for prevention and treatment of neurodegenerative disorders. This work aimed to explore the potential of a leaf extract from Harrisonia abyssinica to modulate the neurobehavioral, biochemical and histopathological activities induced experimentally by Al in vivo. Rats subjected to Al treatment displayed a reduction in learning and memory performance in a passive avoidance test accompanied by a decrease in the hippocampal monoamine and glutamate levels in addition to suppression of Bcl2 expression. Moreover, malondialdehyde (MDA), inflammatory markers (TNF-α, IL-1β), apoptotic markers (caspase-3 and expression of Bax) and extracellular regulated kinase (ERK1/2) levels were elevated along with acetylcholinesterase (AChE) activity, histological changes and marked deposition of amyloid β plaques in the hippocampus region of the brain tissues being observed in Al-treated animals. Concomitant administration of the high dose of H. abyssinica (200 mg/kg b.w.) restored nearly normal levels of all parameters measured, rather than the low dose (100 mg/kg b.w.), an effect that was comparable to the reference drug (rivastigmine). Molecular docking revealed the appropriate potential of the extract components to block the active site of AChE and ERK2. In conclusion, H. abyssinica leaf extract conferred neuroprotection against Al-induced neurotoxic effects, most likely due to its high phenolic and flavonoid content.


2014 ◽  
Vol 675-677 ◽  
pp. 1608-1611 ◽  
Author(s):  
Jin Yang Lin ◽  
Zhuo Ying Zhang

The present study was carried out to investigate anti-hypoxia and anti-fatigue activities of flavonoids from bark of Eucommia ulmoides (FEU) in mice. The animal were divided into four groups: control (C) group, low-dose FEU treated (LF) group, intermediate dose FEU treated (IF) group and high-dose FEU treated (HF) group. The treated groups received FEU (5, 15, 45mg/kg), while the control group received saline solution for 28 days. After 28 days, anti-hypoxia activity of FEU was assessed by the normobarie hypoxia test and anti-fatigue activity of FEU was assessed by the forced swimming test. The data showed that FEU could prolong survival time of oxygen deprivation and exhaustive swimming time by reducing BLA and BUN levels and increasing liver glycogen and muscle glycogen contents. Therefore, FEU had anti-hypoxia and anti-fatigue activities.


2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Romina Tanideh ◽  
Omid Farshad ◽  
Akram Jamshidzadeh ◽  
Aida Iraji

Objective. Manganese (Mn) has been reported, through dietary and occupational overexposure, to induce neurotoxicity named manganism. Pentoxifylline (PTX) administration attracts much attention considering the beneficial properties of PTX, as an anti-inflammatory and smooth muscle relaxation agent. This in vivo study aims to evaluate the effect of PTX on manganism in rat model. Materials and Methods. Thirty adult male Sprague Dawley rats received MnCl2 (100 mg/kg, i.p. on days 1, 3, and 7) during a week alone or in combination with PTX (300 mg/kg, i.p. every day for 8 consecutive days on manganism rat model). Several locomotor activity indices, as well as biomarkers of oxidative stress, were monitored in the brain tissue of Mn-exposed animals. Results. It was found that PTX supplementation (300 mg/kg, i.p.) deteriorated the Mn-induced locomotor deficit. This drug also increased the Mn brain accumulation as well as reactive oxygen species (ROS) and lipid peroxidation products in the manganism rat model. Moreover, the levels of total antioxidant capacity (TAC) and glutathione (GSH) were shown to be reduced significantly compared to the control group. Conclusion. The results of this study revealed that PTX at a high dose (300 mg/kg) might increase manganism complications. PTX lowers the blood viscosity, improves the tissue perfusion, and increases the Mn levels in the brain.


2020 ◽  
Vol 6 (1) ◽  
pp. 44-50
Author(s):  
IO Osonuga ◽  
AS Faponle ◽  
EN Ezima ◽  
TK Adenowo ◽  
AA Adelegan

Background: The leaves of Telfairia occidentalis (locally known as Ugu) are widely consumed as part of a staple in the southern region of Nigeria. Its nutritional benefits include its rich mineral contents and antioxidant properties. It has been suggested that the leaf extracts may affect blood parameters. Objectives: To investigate the effects of aqueous extracts of T. occidentalis leaves on haematological indices and liver enzymes in rats. Methods: Twenty-four male Wistar rats weighing between 150g and 200g were used for the study. They were categorized into four groups of six rats each viz: high-dose, medium-dose, low-dose, and control groups. The leaf extract was administered in doses of 300mg/kg, 200mg/kg, and 100 mg/kg, respectively, while the control group received distilled water rather than leaf extracts.  Results: There was a dose-dependent decrease in the concentrations of liver enzymes and an increase in blood parameters. There was a significant difference (p = 0.000) in the mean red blood cells countof the control group (7.5±0.2×1012/L) compared to the low-dose group (9.1±0.1×1012/L), the medium-dose group (11.7±0.2×1012/L) and the high-dose group (13.3±0.2×1012/L).For the liver enzymes, there was a significant decrease in the mean AST levels in the high-dose group (42.8±3.5 IU/L), the medium-dose group (53.7±5.7IU/L) and the low-dose group (68.5±3.5IU/L) were compared to the value for the control group (88.6 ±2.5× 1012/L). Conclusions: Using an animal model, Telfairia occidentalis may have hepatoprotective and haemopoietic properties.


1990 ◽  
Vol 9 (1) ◽  
pp. 79-91 ◽  
Author(s):  
D. L. Morgan ◽  
J. R. Bucher ◽  
J. E. Huff ◽  
J. K. Haseman ◽  
S. L. Eustis ◽  
...  

3,3′-Dimethoxybenzidine dihydrochloride (DMOB) was evaluated for chronic toxicity and carcinogenicity because benzidine, a structurally related chemical, is a known human carcinogen, and because of potential human exposure during production of bisazobiphenyl dyes. Previous carcinogenicity studies of DMOB were considered to be inadequate. Toxicology and carcinogenesis studies were conducted by administering 0,80,170, or 330 ppm DMOB (>97.5% purity) in drinking water to groups of F344/N rats for 21 months. Seventy rats of each sex were used in the control group, 45 in the low-dose, 75 in the mid-dose, and 70 in the high-dose group. Ten rats of each sex in the control and 330 ppm dose groups were evaluated after 9 months. After exposure for 9 months, chemical-related neoplastic effects included liver foci, carcinoma of the preputial gland in one male, carcinoma of the clitoral gland in one female, and carcinoma of the Zymbal gland in two male rats. Although designed for 24 months, these studies were terminated at 21 months because significant numbers of exposed rats died with tumors or were sacrificed in moribund condition. Chemical-related nonneoplastic effects were hematopoietic cell proliferation in the spleen, and cystic and centrilobular degeneration and necrosis of the liver. 3,3′-Dimethoxybenzidine was clearly carcinogenic for male and female F344/N rats. After exposure for up to 21 months, significantly increased incidences of neoplasms were observed in multiple sites: skin, Zymbal gland, preputial and clitoral glands, oral cavity, small and large intestines, liver, brain, mesothelium, mammary gland, and uterus of treated rats.


1997 ◽  
Vol 272 (4) ◽  
pp. R1290-R1297 ◽  
Author(s):  
N. Yamaguchi

The present study was designed to test whether endothelin (ET) A and/or B receptors in the adrenal medulla are functionally involved in ET-1-induced catecholamine (CA) release in anesthetized dogs. ET-1 was locally infused into the gland via the left adrenolumbar artery. Plasma CA in adrenal venous and aortic blood was determined by a high-performance liquid chromatography method. In the control group, the local infusion of ET-1 (0.5 microg, 0.4 microM) resulted in a significant increase in CA output. In the presence of a low dose of BQ-123 (5 microg, 16.4 microM), the ET-1-induced CA response was significantly attenuated by approximately 80%. With a high dose of BQ-123 (50 microg, 164 microM), the CA response was further blocked by approximately 95%. This inhibition was significantly greater than that obtained with the low dose of BQ-123. By contrast, a low dose of BQ-788 (5 microg, 15.1 microM) did not significantly affect the CA response. With a high dose of BQ-788 (50 microg, 151 microM), the CA response was only partially inhibited by approximately 70%. The results indicate that BQ-123 significantly inhibited ET-1-induced adrenal CA release in a dose-dependent manner. With the low doses, the CA response was markedly inhibited by BQ-123 but remained unchanged in the presence of BQ-788. Moreover, the high dose of BQ-123 virtually abolished the CA response, whereas BQ-788 failed to do so within the dose range tested. The present study suggests that the ET(A) receptor may play a predominant role in mediating the ET-1-induced CA secretion in the canine adrenal gland in vivo, although the possible involvement of the ET(B) receptor could not completely be excluded under the present experimental conditions.


1999 ◽  
Vol 82 (07) ◽  
pp. 140-144 ◽  
Author(s):  
Ling Sun ◽  
Yugi Hiramatsu ◽  
Joseph H. Gorman ◽  
L. Henry Edmunds ◽  
A. Koneti Rao

SummaryPlatelets play a major role in coagulation mechanisms and anti-GPIIb-IIIa antibodies inhibit tissue-factor induced thrombin generation in in vitro studies. Tirofiban, a nonpeptide selective glycoprotein (GP) IIb/IIIa antagonist, preserves platelet number and function during cardiopulmonary bypass (CPB) in baboons. We tested the hypothesis that platelet inhibition by tirofiban inhibits thrombin generation in vivo. Four groups of baboons (n = 7-12) were perfused for 60 min; all groups received heparin (300 units/kg). The controls received only heparin. The low dose (0.1 μg/kg/min) and high dose (0.3 μg/kg/min) infusion groups received tirofiban for 60 min before and 60 min during CPB. The bolus plus low dose infusion group received a 15 μg/kg bolus before starting CPB and a low dose infusion (0.1 mg/kg/min) only during CPB. At end of CPB, compared to control group (2.99 ± 0.36 nM), prothrombin fragment F1.2 levels were lower (p <0.05) in low dose infusion group (1.65 ± 0.14 nM, mean ± SE) and high dose infusion group (1.71 ± 0.19 nM), but not bolus plus infusion group (2.69 ± 0.49 nM); they remained significantly lower after protamine administration. At end of CPB, thrombin-antithrombin complex levels were lower in high dose infusion group (40.0 ± 11.2 ng/ml, p <0.05) compared to control group (76.2 ± 7.3 ng/ml). These studies indicate that tirofiban inhibits not only platelet aggregation but also thrombin generation in vivo during CPB, and that this effect is demonstrable even in the presence of intense heparin anticoagulation. They underscore the important inhibitory effect of GPIIb-IIIa antagonists on thrombin generation.


Author(s):  
G.A. Miranda ◽  
M.A. Arroyo ◽  
C.A. Lucio ◽  
M. Mongeotti ◽  
S.S. Poolsawat

Exposure to drugs and toxic chemicals, during late pregnancy, is a common occurrence in childbearing women. Some studies have reported that more than 90% of pregnant women use at least 1 prescription; of this, 60% used more than one. Another study indicated that 80% of the consumed drugs were not prescribed, and of this figure, 95% were “over-the-counter” drugs. Acetaminophen, the safest of all over-the-counter drugs, has been reported to induce fetal liver necrosis in man and animals and to have abortifacient and embryocidal action in mice. This study examines the degree to which acetaminophen affects the neonatal liver and kidney, when a fatty diet is simultaneously fed to the mother during late pregnancy.Timed Swiss Webster female mice were gavaged during late pregnancy (days 16-19) with fat suspended acetaminophen at a high dose, HD = 84.50 mg/kg, and a low dose, LD = 42.25 mg/kg; a control group received fat alone.


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