Pharmacokinetics of Gelsemium elegans in female rats

Background:Gelsemium elegans Benth(G.elegans)is a poisonous perennial evergreen vine plant that has been applied in livestock production and veterinary clinical practice.Early studies found that the toxicity of G.elegans showed significant gender differences in rats,but the underlying reasons for this difference are still not well understood.Methods:In order to explore whether the gender differences in the toxicity of G.elegans are related to pharmacokinetic differences,based on the previous pharmacokinetic study of multiple components of G.elegans in male rats,this study used HPLC-MS/MS method established in the laboratory to conduct a pharmacokinetic study of multiple alkaloids in the plasma of female rats after a single gavage administration of G.elegans(dose of 0.1 g/kg).Results:Through detection,17 alkaloid components in the plasma of female rats were identified,and the pharmacokinetic parameters of 11 of these alkaloids were calculated.We find that in female rats.The T_(max)values were generally less than 0.5 h,and the T_(1/2)values exceeded 3 h,with the longest reaching up to 32.80 h half elimination time.Additionally,the C_(max)and AUC results indicated that female rats had generally higher absorption and exposure levels for most alkaloids.Conclusion:These results suggest that the reason for the differences in the toxicology of G.elegans may be related to the absorption and exposure of gelsemidine-type alkaloids in animals.

Oxidized palm oil impairs reproductive functions and architectures in female rats

Objective:To evaluate the effects of three oxidized palm oil diets(OPD)on female rat reproductive function.Methods:Forty-four female Wistar rats presenting five consecutive and regular estrous cycles were divided into 4 groups.The rats were fed with:a standard diet,70%of standard diet+30%oxidized palm oil diet(OPD1),OPD1+5 g of boiled yolk egg(OPD2)and OPD1+10%sucrose(OPD3)for 125 days,respectively.During the feeding period,morphometric,estrous cycle,sexual behavior,gestation,biochemical and histomorphometric parameters were evaluated.Results:All OPDs significantly increased abdominal circumference,body mass index and Lee index coupled to an irregularity and lengthening of the estrous cycle.They significantly decreased appetite and consumption behaviours,quantic pregnancy index,fertility rate,implantation sites and index,serum progesterone and high-density lipoprotein levels,increased pre-implantation losses,anti-implantation activities,serum estradiol,triglycerides,total and low-density lipoprotein-cholesterol levels,and impaired brain and ovaries oxidative status.Histomorphometric examinations revealed increases in the number of atresic and primary follicles and decreases in secondary,tertiary,Degraaf,total and corpus luteum follicles in ovaries coupled to a neurodegeneration of hypothalamic anteroventral periventricular neurons in the OPD groups compared to the standard diet group.Conclusions:The three OPDs induce obesity and impair the female reproductive function,especially OPD2 and OPD3.These findings contribute to a better understanding of the adverse effects of palm oil bleaching on the reproductive function in female rats,which could be useful in the management of women with obesity-related sexual dysfunction.

Test of the Popular Benzodiazepine Alprazolam in a Positive Conditioned Place-Preference Model in Female Rats

The benzodiazepines were introduced into medical practice during the 1960s. At the time, they represented a safer alternative to extant therapies used for anxiety, such as the barbiturates. However, on September 23, 2020, the United States FDA indicated that more is needed to be known about the initiation, continuation, and discontinuation of the use of these widely-used drugs with publication of the announcement “to address the serious risks of abuse, addiction, physical dependence, and withdrawal reactions, the U.S. Food and Drug Administration (FDA) is requiring the Boxed Warning be updated for all benzodiazepine medicines.” Because for many years, there has been a sparsity of research on these drugs, relevant information is unfortunately lacking at this critical time. It is therefore valuable to (re)establish animal models and begin to collect relevant data. We here use a model of conditioned place preference (CPP) which suggests that the representative benzodiazepine alprazolam induces positive place preference in female rats.

Expression of type-Ⅰ collagen and matrix metalloproteinase-9 mRNA in bone of castrated adult female rats:effects of estrogen

Abstract Objectives To elucidate the molecular changes of bone collagen during the development of postmenopausal osteoporosis and to investigate the molecular effects of estrogen replacement. Methods An adult ovariotomy rat model was used. Type Ⅰ collagen and matrix metalloproteinase 9 (MMP 9) expressions in bone tissues of rats treated by sham surgery (SH), bilateral ovariotomy (OVX) and OVX with estradiol (OVX E2) were analysed at mRNA level by using dot blot technique. The distribution of mRNA of these two genes in bone tissues was studied by in situ hybridization. Results The expression levels of both type Ⅰ collagen and MMP 9 in bone tissues of OVX rats were higher than those of SH group, while treated with estradiol, the expression of both genes declined to some degree. In situ hybridization showed that type Ⅰ collagen mRNA located in osteoblasts, whereas MMP 9 was mainly expressed in osteoclasts, some lining cells on bone surface, and some mononuclear cells in bone marrow. Conclusions The reduction of high bone turnover in osteoporotic bone tissues induced by estrogen replacement may result from alterations in gene expression related to bone formation and bone resorption. These alterations are consistent with the changes observed previously by histomorphometry and biochemical markers of bone metabolism on OVX animals and postmenopausal osteoporosis.

Acute and Reproductive Toxicity of the Aqueous Extract of the Dry Seeds of <i>Aframomum daniellii </i>on the Female Wistar Rat Strain

This work was designed to investigate the acute and reproductive toxicity activity of the aqueous extract of the dry seeds of Aframomum daniellii on the female rats. The acute toxicity of the aqueous extract of Aframomum daniellii (A. daniellii) was evaluated with 6 female rats which were divided into 2 groups (1 Test group and the Control group) of 3 female rats each. The control group received distilled water (10 mL/kg/po) and the test group received a single dose of extract of A. daniellii at the dose of 2000 mg/kg. The reproductive toxicity was evaluated using 45 adult female rats which were divided into 5 groups. Group I, received distilled water (1 mL/100 g/po, neutral control);group II, received Clomiphene citrate (600 μg/kg/po, positive control);Groups III, IV and V (trials) received aqueous extract of A. daniellii at doses of 100, 200 and 400 mg/kg/po respectively. The animals were treated daily for 14 days. From the 6th day of treatment, the rats were mated with males of proven fertility for 8 days. On day 22, after laparotomy and delivery, the number of implantation sites, corpora lutea, resorption sites and pups were recorded. Concerning the acute toxicity, it was observed that, after the single dose of 2000 mg/kg administration of the aqueous extract of the dry seeds of A. daniellii, no deaths were recorded. Concerning the reproductive toxicity, no implantation and gestation were observed when compared to the control. However, the aqueous extract of A. daniellii caused a significant (p < 0.001) increase in serum estrogen levels in all treated rats when compared to the control. These results indicate that, the aqueous extract of the dry seeds of A daniellii is weakly toxic, but could negatively affect some reproductive parameters.