Sub-acute Toxicity Profile Research Articles

Acute and Sub-acute Toxicity Profile of Carpolobia lutea Leaf Extract in Rats

Acute and Sub-acute Toxicity Profile of Carpolobia lutea Leaf Extract in Rats

Acute and sub-acute oral toxicity profile of Acorus calamus (Sweet flag) in rodents

ObjectiveTo determine the acute and sub-acute oral toxicity profile of the hydroalcoholic extract of Acorus calamus (HAE-AC) in mice and rats respectively. MethodsIn acute toxicity study, mice were assessed to any alteration of general behavior and mortality rate within 24 h. Further, in sub-acute toxicity study, rats were used for assessment of mortality, body weight, hematological, biochemical and histopathological changes. ResultsSingle oral administrations of the HAE-AC 2 500–10 000 mg/kg induced increase in general behavioral abnormalities in mice. The mortality rate also increased with increasing dosage (median lethal dose; LD50 = 5 070.59 mg/kg). Daily single oral doses of HAE-AC 200, 500 and 1 000 mg/kg were observed to be well tolerated behaviorally after 28 days of dosing and induced no significant changes in body and organs weights of rats. Further, a mild rise in the levels of alanine transaminase (ALT), aspartate transaminase (AST) and histopatholological changes in liver tissue was noted at 1 000 mg/kg dose of HAE-AC. ConclusionsOverall, the findings of this study indicate that, HAE-AC is non-toxic and has at high dose, a mild but acceptable toxicity potential.

Acute and sub-acute toxicity study of hydroalcoholic fruit extract of Pithecellobium dulce

This study was carried out to evaluate the acute and sub-acute toxicity profile of the hydroalcoholic fruit extract (HAEPD) of Pithecellobium dulce (Leguminosae). Albino rats were treated orally with 100, 200 and 500 mg kg−1 bodyweight (BW) of HAEPD for 90 days to assess its sub-acute toxicity. HAEPD at single doses of 100, 500, 1000, 2000 and 4000 mg kg−1 BW was also administered to rats to assess its acute toxicity. The rats were observed for physical discomfort, BW change and feeding habits. Pithecellobium dulce did not cause any abnormal changes in haematological or biochemical parameters. Pathologically, no gross abnormality in the tissue architecture was observed. The LD50 was found to be 3916 mg kg−1 BW and potential effective doses for efficacy studies are 100 and 300 mg kg−1 BW as the minimum and maximum doses, respectively. It is concluded that HAEPD can be used safely for experimental and clinical trials.

Poly propyl ether imine (PETIM) dendrimer: A novel non-toxic dendrimer for sustained drug delivery

In the present study, an attempt was made to study the acute and sub-acute toxicity profile of G3–COOH Poly (propyl ether imine) [PETIM] dendrimer and its use as a carrier for sustained delivery of model drug ketoprofen. Drug-dendrimer complex was prepared and characterized by FTIR, solubility and in vitro drug release study. PETIM dendrimer was found to have significantly less toxicity in A541 cells compared to Poly amido amine (PAMAM) dendrimer. Further, acute and 28 days sub-acute toxicity measurement in mice showed no mortality, hematological, biochemical or histopathological changes up to 80 mg/kg dose of PETIM dendrimer. The results of study demonstrated that G3–COOH PETIM dendrimer can be used as a safe and efficient vehicle for sustained drug delivery.

Acute and sub-acute toxicological assessment of the aqueous seed extract of <i>Persea americana</i> Mill (Lauraceae) in rats

The aqueous seed extract of Persea americana Mill (Lauraceae) is used by herbalists in Nigeria for the management of hypertension. As part of our on-going scientific evaluation of the extract, we designed the present study to assess its acute and sub-acute toxicity profiles in rats. Experiments were conducted to determine the oral median lethal dose (LD(50)) and other gross toxicological manifestations on acute basis. In the sub-acute experiments, the animals were administered 2.5 g/kg (p.o) per day of the extract for 28 consecutive days. Animal weight and fluid intake were recorded during the 28 days period. Terminally, kidneys, hearts, blood/sera were obtained for weight, haematological and biochemical markers of toxicity. Results show that the LD(50) could not be determined after a maximum dose of 10 g/kg. Sub-acute treatment with the extract neither affected whole body weight nor organ-to-body weight ratios but significantly increased the fluid intake (P < 0.0001). Haematological parameters and the levels of ALT, AST, albumin and creatinine were not significantly altered. However, the concentration of total proteins was significantly increased in the treated group. In conclusion, the aqueous seed extract of P. americana is safe on sub-acute basis but extremely high doses may not be advisable.

English

&nbsp; Faidherbia albida&nbsp;(Del.) A. Chev (mimosoidae) is widely used in African traditional medicine (ATM) for management of fever, diarrhoea and human trypanosomiasis.Acute and sub-acute toxicity profiles of ethanolic stem bark extract of&nbsp;F. albida&nbsp;were evaluated in wistar albino rats. The acute toxicity was studied using the method of Lorke (1983). In the sub-acute toxicity study, four groups of six rats per group were used. The control group (1) received 10 ml normal saline/kg body weight while groups 2, 3 and 4 received oral&nbsp;daily doses of 125, 250 and 500 mg extract/kg body weight respectively for 21 days. The effects of the extract on clinical signs, feed and water intake, body weight changes, haematology, plasma biochemical parameters, relative organ weight (ROW) were evaluated. The oral LD50&nbsp;of the extract was estimated to be greater than 5000 mg/ kg body weight. The extract produced slight increase in body weight of rats given 125 mg extract/kg body weight. However, dose-dependent highly significant (P &lt; 0.01) decrease in body weight was observed at 250 and 500 mg/ kg-treated rats in weeks 2 and 3 of the study. Feed and water intake was not affected by the treatment. ROW for all organs was not affected by the treatment except significant (P &lt; 0.05) increase in the testes of rats treated with 250 and 500 mg extract/kg body weight. Although the treatment elicited highly significant (P &lt; 0.01) changes in the levels of the hepatic and some of the haematological parameters, they were within the normal reference range for rats. This study revealed that while the stem bark of the plant may be considered relatively safe when used sub-acutely, further investigation is needed to ascertain its effect on the male reproductive system as well as its effect on chronic administration.&nbsp;&nbsp;&nbsp; &nbsp; Key words:&nbsp;Faidherbia albida,&nbsp;toxicity, haematology, liver function, testes.

Sub-Acute Toxicity Profile of Fixed Dose Combination of Pirotum (Cefpirome-Sulbactam) in Swiss Albino Mice and Wistar Rat

Sub-Acute Toxicity Profile of Fixed Dose Combination of Pirotum (Cefpirome-Sulbactam) in Swiss Albino Mice and Wistar Rat

Toxicity And Immunomodulatory Activity Of Fractions Of &lt;i&gt;Hibiscus sabdariffa&lt;/i&gt; Linn (Family Malvaceae) In Animal Models

This study evaluated immunomodulatory properties and the sub-acute toxicity profile of two fractions of the aqueous alcoholic extract of the dried calyx of Hibiscus sabdariffa in experimental animals. Immunomodulatory activity was evaluated using red blood cell-induced immunostimulation. The fractions were not found to be toxic after 7-day administration, though there was severe weight loss with the residual water-soluble fraction (RWSF) and weight gain with the ethyl acetate soluble fraction (EAC). The EAC exhibited a significant dose-dependent immunostimulation (p<0.05) higher than that observed for levamisole (positive control). The residual water-soluble fraction exhibited immunostimulatory activity at 100 mg/kg body weight. The two fractions caused a significant reduction in production of tissue necrosis factor-alpha and an increase in interleukin 10 (IL-10).

In vivo toxicity, pharmacokinetics, and anti-human immunodeficiency virus activity of stavudine-5'-(p-bromophenyl methoxyalaninyl phosphate) (stampidine) in mice.

We have evaluated the clinical potential of stavudine-5'-(p-bromophenyl methoxyalaninyl phosphate(stampidine [STAMP]), a novel aryl phosphate derivative of stavudine, as a new anti-human immunodeficiency virus (anti-HIV) agent, by examining its acute, subacute, and chronic toxicity profile in mice as well as by testing its antiviral activity in a surrogate human peripheral blood lymphocyte (Hu-PBL)-SCID mouse model of human AIDS. STAMP was very well tolerated in BALB/c and CD-1 mice, without any detectable acute or subacute toxicity at single intraperitoneal or oral bolus doses as high as 500 mg/kg of body weight. Notably, daily administration of STAMP intraperitoneally or orally for up to 8 consecutive weeks was not associated with any detectable toxicity at cumulative dose levels as high as 6.4 g/kg. Micromolar concentrations of the active STAMP metabolite in plasma were rapidly achieved and maintained for more than 4 h after parenteral as well as oral administration of a nontoxic 100-mg/kg bolus dose of STAMP. In accordance with its favorable pharmacokinetic profile and in vitro potency, STAMP exhibited dose-dependent and potent in vivo anti-HIV activity in Hu-PBL-SCID mice against a genotypically and phenotypically nucleoside analog reverse transcriptase inhibitor (NRTI)-resistant clinical HIV type 1 (HIV-1) isolate (BR/92/019; D67N, L214F, T215D, K219Q) at nontoxic dose levels. The remarkable in vivo safety and potency of STAMP warrants the further development of this promising new antiretroviral agent for possible clinical use in patients harboring NRTI-resistant HIV-1.

Research on medicinal plants and traditional medicine in Africa.

Research on medicinal plants and traditional medicine in Africa.