scholarly journals Median lethal dose and sub-chronic toxicity profile of Azadirachta indica A. Juss. leaf hexane and ethyl acetate fractionated extracts on albino rats

2020 ◽  
Vol 3 (3) ◽  
pp. 007-022
Author(s):  
Ibrahim Sani ◽  
Rabi’u Aliyu Umar ◽  
Rabi’u Aliyu Umar ◽  
Umar Zaki Faruq ◽  
Fatima Bello

Azadirachta indica A. Juss. (Neem) is a multipurpose medicinal plant, traditionally used in the treatment of various human ailments. This plant is tagged as having high toxicity profile, and the toxicity might be related to the polarity nature of the solvent used for extraction. Hence, this research was aimed at screening the toxicity profile of Azadirachta indica leaf fractionated extracts using Albino rats. A. indica leaf was collected, authenticated and extracted using 95 % methanol then fractionated with hexane and ethyl acetate. Median lethal dose (LD50) of each fraction was determined using single oral dose of 5,000 mg/kg body weight (b. wt.) to five (5) rats. For the sub-chronic toxicity screening, the fractions were administered to groups of rats at different concentrations. Group 1 served as control, groups 2-5 received 900, 1800, 2700 and 3600 mg/kg b. wt. respectively. After 28 days, biochemical indices of hepatic and renal functions as well as haematological and histopathological parameters were analyzed. LD50 of each of the fractions was greater-than 5000 mg/kg b. wt. All the extract fractions at the administered doses, significantly (P<0.05) altered the serum levels of some biochemical indices of the hepatic and renal functions, as well as the levels of some haematological parameters. For the histopathology, hepatic congestion, periportal inflammation, distortion, infiltration and haemorrhage were observed at 1800-3600 mg/kg b. wt. Hence, these results indicated that using hexane or ethyl acetate as solvent of extraction, A. indica leaf extracts might not be considered safe at the administered sub-chronic doses.

Author(s):  
Siva Kumar T ◽  
Shobha Rani A ◽  
Sujatha K ◽  
Purushotham B ◽  
Neeraja P

ABSTRACTObjective: The present study was designed to find out the acute median lethal dose (LD50) of ammonium sulfate (inorganic fertilizer) in Wister albino rats.Methods: A single dose of ammonium sulfate dissolved in distilled water (Milli-Q) and administered intraperitoneally at concentrations of 10, 30, 50,70, 90, 110, 130, and 170 mg/kg body weight, respectively, to experimental animals, and then, they were observed every 3 hrs from prior dose giventime, later 6 hrs, 12 hrs, 24 hrs, to 48 hrs of noticing any abnormal behaviors and toxic signs, symptoms. After 48 hrs, counted the number of ratsdeparted in each group and mortality percentage was calculated.Results: The obtained results were evaluated by the Statistical Probit Analysis Method and 48 hrs LD value for albino rats was found tobe 91.5 mg/kg. At a single dose of 10 mg/kg, there is no morality and toxic behaviors were observed. Therefore, this concentration is considered asno observed adverse effect level dose.Conclusion: From the earlier consequences, identification and evaluation of the LD5050 against ammonium sulfate is crucial for understanding thehyperammonemia because ammonium sulfate has been highly utilized as inorganic fertilizer in agriculture and household gardens. Thus, theknowledge about toxic impacts of ammonia useful for clinical or toxicological approaches; however, the toxicity data are unclear. Hence, the in vitroLD50 evaluations of target chemical in Wistar rats is highly associated toward in ammonia-related peculiar disorders perceptive and therapy.Keywords: Ammonium sulfate, Fertilizer, Median lethal dose, Mortality, No observed adverse effect level.


Author(s):  
Ibrahim Sani ◽  
Rabi’u Aliyu Umar ◽  
Sanusi Wara Hassan ◽  
Umar Zaki Faruq ◽  
Fatima Bello ◽  
...  

Snake venom enzymes are the key substances involved in snake venom toxicity. Thus, inactivating these enzymes is generally considered to be the fundamental step in the management of snakebite. Conventionally, snakebite envenomation is treated parenterally with serum-based antivenins, and adjuvants to these antivenins are required for maximum protection of victims. Hence, this research was aimed at evaluating the inhibitory effect of Azadirachta indica leaf extracts on Naja nigricollis Reinhardt venom enzymes and screens for their antivenom adjuvant effects. A. indica leaf was collected, authenticated and extracted using 95% methanol followed by fractionation using hexane and ethyl acetate. The venom enzymes inhibition assays was evaluated using in vitro methods, while, adjuvant effect was screened using Albino rats. The results revealed that both the hexane and the ethyl acetate fractions showed capability of inhibiting the venom enzymes significantly (P<0.05) when compared with the venom controls in varying degrees of efficacies. For the adjuvant effect, no significant effect (P>0.05) of the venom at the administered dose was observed on bleeding time, clotting time, defibrinogenating and haemorrhagic effects compared to the normal control. However, the size of necrotic lesion and the percentage haemolysis were significantly (P<0.05) higher in the venom control rats. Both the hexane and the ethyl acetate fractions significantly mitigated these effects in the treated animals. The degree of protection was about 3 folds more than when the antivenin was used alone. Finally, these findings would be of importance in the area of drug development with a view to actualizing the substitution or enhancing the effect of conventional snakebite therapeutic options.


Author(s):  
O. S. Onwukwe ◽  
J. N. Ukwuani ◽  
A. O. Onyemelukwe ◽  
N. C. Azubuike ◽  
A. C. Onuba ◽  
...  

Aim: To evaluate the sub-acute toxicity profile of fractions of Vitex doniana using adult albino rats. Study Design: An experimental study that lasted for 28 days. Place and Duration of Study: Department of Medical Laboratory Sciences and Animal House Unit, College of Medicine, University of Nigeria Enugu Campus, between January 2019 and March 2019. Methodology: Methanol, ethyl acetate and hexane fractions of V. doniana were orally administered to 6 groups of animals at doses of 150 mg/kg and 300 mg/kg body weight for each fraction, for 28 days. At the end of the administration, the animals were sacrificed. Body weight changes, Relative Organ Weights (ROW), haematological analysis, serum biochemical assay and histopathological changes of vital organs were used to evaluate the potential toxic effects of the fractions after treatments. Results: The fractions had no adverse effects on the body weights, ROW and gross appearance of the tissues. There were no significant changes in the haematological and biochemical parameters of the treated animals compared to the controls. Histological assessment of the excised organs also showed no overt pathological changes apart from thickened alveolar septa in the lungs of the animals that received methanol and ethyl acetate fractions. Conclusion: The polar fractions of V. doniana at the doses tested did not induce any toxic changes in the treated animals.


Author(s):  
Brijender Bhushan ◽  
Prabhu Narain Saxena

Present study was aimed to evaluate the median lethal dose (LD50) of two broadly used, type II pyrethroid pesticides Cypermethrin and Beta-cyfluthrin against Wistar albino rats. The albino rats corresponding to experimental sets were orally administrated different doses of selected pyrethroids for estimation of median lethal dose. LD50 has been calculated by Log-dose/probit regression line method, and came out to be 416.98 and 354.8 mg/Kg b.wt. for Cypermethrin and Betacyfluthrin respectively. Difference in the median lethal of these compounds may be a consequence of structural differences


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Rofiyat Omolara Raji ◽  
Hadiza Lami Muhammad ◽  
Abdulkadir Abubakar ◽  
Sophia Shekwoyan Maikai ◽  
Habibat Feyishara Raji

Abstract Background Gymnema sylvestre is a reputable medicinal plant commonly explore for the management of diabetes and other ailments in traditional medicine. In the present study, we investigated the phytochemical compositions and effect of crude extract, hexane, and ethyl-acetate fractions of Gymnema sylvestre on biochemical and hematological parameters of Wistar rats. Methods Albino rats were distributed randomly into a control group and nine treatment groups orally administered crude extract and fractions of Gymnema sylvestre (100, 300, and 600 mg/kg BW) for 21 days. Liver and kidney function indices, as well as hematological parameters, were monitored. Results Our results revealed that the crude methanol extract contains flavonoids (8.56 ± 0.50 mg/g), alkaloids (13.84 ± 0.67 mg/g), total phenol (1.98 ± 0.50 mg/g), saponins (23.85 ± 0.35 mg/g) and tannins (16.00 ± 0.34 mg/g). The crude methanol, ethyl acetate and n-hexane fractions of Gymnema sylvestre had LD50 greater than 5000 mg/kg BW in acute oral toxicity test. The extract and fractions at 300 and 600 mg/kg BW cause loss of body weight of the rats, significantly altered (p < 0.05) the levels of biochemical indices including the aspartate transaminases, alanine transaminase, alkaline phosphates, bilirubin, proteins, urea, creatinine, and white blood cells (WBC) counts when compared with the non-treated control. However, the extract and fractions at 100 mg/kg BW did not cause any significant (p > 0.05) alterations to the levels of biochemical and hematological parameters when compared with the non-treated control. Conclusion Gymnema sylvestre at sub-acute doses of 300 and 600 mg/kg BW could compromise the functional integrity of the rats’ liver and kidney. The study, therefore, suggested the use of Gymnema sylvestre for oral remedy at a dose of 100 mg/kg or below.


Author(s):  
Ibrahim Sani ◽  
Rabi’u Aliyu Umar ◽  
Sanusi Wara Hassan ◽  
Umar Zaki Faruq ◽  
Fatima Bello

The lethality of snake venom is mainly attributed to its phospholipase A2 component that hydrolyzes cellular phospholipids, leading to the release of arachidonic acid that generates potentially toxic reactive oxygen species (ROS). Imbalance between excessive generation and poor removal of ROS causes lipid peroxidation leading to cellular damage. Hence, this research was aimed at evaluating the antioxidant-enhancing effect of Azadirachta indica leaf fractionated extracts on Naja nigricollis venom in albino rats. A. indica leaf was collected, authenticated and extracted using 95% methanol followed by fractionation using hexane and ethyl acetate. Ferric reducing antioxidant power assay was used for the in vitro test, while, in vivo experiments were conducted using Albino rats. The in vitro antioxidant effect of the hexane and ethyl acetate fractions presented ferric reducing power of 68.80 ± 1.40% and 71.54 ± 2.12% respectively. This are closely related to those of ascorbic acid (78.50 ± 2.80%) and α-tocopherol (75.00 ± 1.85%). The results of the in vivo tests indicated that a single injection (0.195 mg/kg b. wt.) of N. nigricollis venom caused significant (P<0.05) elevation of hepatic and renal ROS levels (7 and 8 folds respectively) with a concomitant increase in lipid peroxidation (LPO) compared to the control group. The ROS levels were decreased significantly leading to the decrease in the level of LPO in the envenomed rats treated with the hexane and ethyl acetate fractions compared to the venom control. The treatments significantly (P<0.05) increased the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) in both the hepatic and renal homogenates compared to the venom control. The degree of protection against LPO by reducing the levels of ROS as well as increasing the activities of the antioxidant enzymes has significantly (P<0.05) increased when combine treatment of standard antivenin and any of the hexane or ethyl acetate fractions was considered compared to when each of them was used alone. Based on these findings, it has been established that, the tested extracts have antioxidant as well as antioxidant-enhancing effects against the oxidative toxicity of N. nigricollis venom.


2020 ◽  
Vol 14 (4) ◽  
pp. 295-311
Author(s):  
Ada Gabriel ◽  
Mamman Mohammed ◽  
Mohammed G. Magaji ◽  
Yusuf P. Ofemile ◽  
Ameh P. Matthew ◽  
...  

Background: Snakebite envenomation is a global priority ranked top among other neglected tropical diseases. There is a folkloric claim that Uvaria chamae is beneficial for the management of snakebite and wounds in African ethnobotanical surveys. Besides, there are many registered patents asserting the health benefits of U. chamae. Objective: This study aimed to investigate U. chamae’s potentials and identify candidates for the development of tools for the treatment and management of N. nigricollis envenomation. Methods: Freshly collected U. chamae leaves were air-dried, powdered, and extracted in methanol. The median lethal dose of the extract was determined and further fractionated with n-hexane, n-butanol and ethyl acetate. Each fraction was tested for neutralizing effect against venom-induced haemolytic, fibrinolytic, hemorrhagic, and cytotoxic activities. Results: U. chamae fractions significantly (p<0.05) neutralized the haemolytic activity of N. nigricollis venom in n-butanol; 31.40%, n-hexane; 33%, aqueous residue; 39.60% and ethyl acetate; 40.70% at the concentration of 100mg/ml of each fraction against 10mg/ml of the snake venom when compared to the positive control. The fibrinolytic activity of N. nigricollis venom was significantly (p<0.05) neutralized in n-hexane at 73.88%, n-butanol; 72.22% and aqueous residue; 72.22% by the fractions of U. chamae. In addition, haemorrhagic activity of N. nigricollis venom was significantly (p<0.05) neutralized by U. chamae fractions at the concentrations of 100mg/ml, 200mg/ml and 400mg/ml except for n-butanol and aqueous residues at 400 mg/ml. Conclusion: U. chamae leaves fractions possess a high level of protection against N. nigricollis venoms-induced lethality and thus validate the pharmacological rationale for its usage in the management of N. nigricollis envenomation.


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