scholarly journals Study of Reproductive Toxicity of the Liposomal Photosensitizer Lipophthalocyan

Drug Research ◽  
2021 ◽  
Author(s):  
Olga Konyaeva ◽  
Nataliya Kulbachevskaya ◽  
Vera Chaley ◽  
Nadezhda Ermakova ◽  
Pavel Varaksa ◽  
...  

Abstract Objective Study of embryotoxicity, teratogenicity and reproductive toxicity of the new drug Lipophtalocyan in rats. Material and Methods Studies were conducted on 210 non-inbred female rats and 105 non-inbred male rats. The drug was administered daily via i. v. injection for 48 days (males) and for 15 days (females) in 2 total doses corresponding to the therapeutic dose (TD) for mice when converted to rats and 10 TD. Results and Conclusion When mating with intact female rats, no changes in sexual behavior were observed, but the index of the ability to fertilize and conceive decreased when compared to the values of the control group by 35–40% (TD index=60%) and by 75–80% (10 TD index=20%). The index of the ability to fertilize and conceive differed from the values of the control group by 90% (TD index=5%) and by 15% (10 TD index=80%). There were no differences in the indicator of embryotoxicity and teratogenicity in intact and drug-treated female rats, compared with the control group. Lipophtalocyan has a negative effect on the male and female reproductive function in rats and has an embryotoxic effect according to the index of the ability to fertilize and conceive, as well as the indices of preimplantation and post-implantation fetal death. The drug does not have a teratogenic effect, neither it affects the physical development of offspring or the rate of maturation of sensory-motor reflexes during feeding.

2021 ◽  
Vol 54 (1) ◽  
pp. 52-61
Author(s):  
NR Shepelskaya ◽  
YaV Kolyanchuk

Aim. Studying the effect of generic pesticides cyproconazole (98 %) and two samples of epoxiconazole (epoxiconazole 1 — 95,75 % and epoxiconazole 2 — 98,7 %) on the reproductive system of male and female Wistar Han rats at the level of the organism when exposed during gametogenesis, identification and characterization of their hazard, as well as assessment of the risk of reproductive toxicity of these compounds. Materials and Methods. The test samples were administered daily (5 days a week) by oral gavage at doses of 0.2 and 2.0 mg/kg for cyproconazole and 0.5 and 2.0 mg/kg for epoxiconazoles during 11 weeks for males, and 10 weeks for females. Also, there were kept intact males and females, intended for crossover mating with experimental animals. After the end of the exposure, functional indicators of the state of the gonads and the ability of animals to reproduce offspring were studied. The duration and the frequency of each stage of the estrous cycle in female rats and the number of motile sperm, the total amount of sperm and the number of abnormal forms of germ cells of the male rats were studied. The reproductive function state in females was evaluated on day 20th of pregnancy. Thereby the number of corpora lutea in the ovaries, number of alive, dead and resorbed foetuses and embryos, the foetus weight, total weight of litters were registered. The studies were carried out in accordance with the recommendations of the Bioethics Commission and the Centre’s standard operating procedures, developed in accordance with the recommendations and requirements of Good Laboratory Practice (GLP). Conclusions. Test substances at a maximum dose of 2.0 mg/kg of body weight have reproductive toxicity and endocrine-disruptive effect, exerting a significant antiandrogenic effect on males and antiestrogenic effect on female rats. No-observed-adverse-effect-level (NOАEL) for gonadal and reproductive toxicity for male and female Wistar Han rats were established. They are 0.2 mg/kg body weight for cyproconazole and 0.5 mg/kg body weight for epoxiconazole. Key Words: azole fungicides, cyproconazole, epoxiconazole, reproductive toxicity, antiandrogenic and antiestrogenic effects, Wistar Han rats.


2020 ◽  
Vol 8 (A) ◽  
pp. 452-456
Author(s):  
Assylgul Suleimen ◽  
Roza Yesimova ◽  
Bibigul Rakhimova ◽  
Gulnaz Suleimen ◽  
Aidana Yerubay ◽  
...  

BACKGROUND: The Aral Sea crisis is recognized as one of the global environmental problems of our time. The extreme environmental situation in the region is caused by massive chemical pollution of the territory for several decades by high doses of pesticides, herbicides, dumping of industrial waste into the rivers that feed the Aral Sea. As a result of the Aral Sea desiccation, aridization of the territory, climate change, and salinization of soil and water occurred. This led to increased mineralization of precipitation, climate change, the spread and deposition of dust on an area of about 25 million hectares. One of the factors in reducing fertile activity in humans is a decrease in spermatogenesis activity. Based on identified trends, WHO is forced to review the main indicators of spermograms in the direction of their reduction. AIM: To study the effect of dust and salt aerosols of the Aral Sea on reproductive function, rat testes were studied after 7 and 24 days of inhalation administration. MATERIAL AND METHODS: Some morphometric parameters of the testes were evaluated: The diameter of the convoluted seminiferous tubules and the thickness of the germinal epithelium. The obtained comparative morphological and histological characteristics of the testes of the control and experimental groups indicate the negative effect of the components of dust and salt aerosols of the Aral Sea on the reproductive function of male rats. RESULTS: The thickness of the epithelial spermatogenic layer in the second group of rats is on average 64.52 μm, which is significantly less compared to the control group (81.3 μm). The thickness of the epithelial spermatogenous layer in the third group is on average within 73.36 μm, which is significantly less than in the control group (81.3 μm), but more than in the group exposed to dust and salt aerosols for 7 days (64, 52 μm). CONCLUSION: The study revealed that the impact of dust and salt aerosols of the Aral Sea leads to a change in the morphological and histological characteristics of the testes of animals. In experimental groups, a decrease in the diameter of the convoluted seminiferous tubule and a decrease in the thickness of the epithelial spermatogenic layer were observed. This indicates the negative effect of the components of dust and salt aerosols of the Aral Sea on the reproductive function of male rats exposed to dust for 7 and 24 days.


2019 ◽  
Vol 84 (4) ◽  
pp. 36-41
Author(s):  
Ya.V. Kolianchyk

Objective. Identification of hazard and assessment of the risk of gonado- and reproductive toxicity of two generic pesticides of technical-grade carbendazim of different purity bin male and female Wistar Han rats. Materials and Methods. Carbendazim with the purity of 98 % (C1) and 98.1 % (C2) was intragastrically administered on the daily basis, excluding Saturday and Sunday, at the doses of 2.5 and 25 mg/kg body weight in three groups of animals (20 males and female rats in each) during 10 weeks (forfemales) and 11 weeks (for males). Control animals received an equivalent amount of the solvent. Intact animals intended for breeding were managed in parallel with the control and experimental animals. After the end of the exposure, functional parameters of the condition of gonads and reproductive ability of the animals were investigated. Females were used to investigate the condition of the oestral cycle, duration and frequency of each stage of it. The condition of the reproductive function in the female rats was considered at Day 20 of pregnancy. Indices of breeding, conception, fertility, pregnancy were established, and the duration of the pre-coitalperiod was considered. Results and Discussion. The data obtained suggest that exposure to two generic substances of carbendazim at the dose of 25 mg/kg body weight during 11 weeks is manifested in general toxic effect (body weight reduction) only in males upon exposure to C2. All test substances in the maximum dose have reproductive toxicity and show significant anti-androgenic action that is manifested as changes in the morphological and functional parameters of the condition of gonads in the experimental groups of male rats. Furthermore, the negative effect on the oestral cycle in experimental female rats exposed to C2 was noted. Conclusion. Based on the obtained results it can be concluded that all test samples of carbendazim have reproductive toxicity at the dose of 25 mg/kg body weight. No-observed-effect level (NOEL) for all test compounds is 2.5 mg/kg body weight. Dose-effect dependence was observed in the range of studies doses.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Murtala Akanji Abdullahi ◽  
Elijah Oladapo Oyinloye ◽  
Akinyinka Alabi ◽  
Aderonke Adeyinka Aderinola ◽  
Luqman Opeyemi Ogunjimi ◽  
...  

Abstract Objectives Several studies have established the ethnobotanical benefits of Pupalia lappacea (PL) in laboratory animals without extensive toxicological evaluation of its safety profiles. Thus, an extensive toxicological investigation of sub-chronic oral administration of the hydroethanol leaf extract of P. lappacea in rodents was carried out in this study. Methods Different groups of rats were treated orally with the extract (10, 50 and 250 mg/kg) daily for 90 consecutive days. The control group received distilled water (10 mL/kg). After 90 days, some rats were left for additional 30 days without treatment for reversibility study. Blood and organs samples were collected for different evaluations at the end of study periods. Results The extract decreased the bodyweights, feeding and water intakes in female rats. PL increased the weights of the liver and kidney in male rats. PL increased the red blood cell (RBC), packed cell volume (PCV), hemoglobin (Hb), triglycerides (TRIG), cholesterol and high density lipoprotein (HDL) contents in rats. PL (250 mg/kg) significantly reduced the sperm motility and serum testosterone level. Cyto-architectural distortions of the testes, liver and spleen were visible. Conclusions The findings showed that P. lappacea is relatively safe at lower doses but cautions should be taken at higher dose.


2015 ◽  
Vol 3 (1) ◽  
pp. 5 ◽  
Author(s):  
Barnabé Lucien Nkono Ya Nkono ◽  
Selestin Dongmo Sokeng ◽  
Paul Désiré Dzeufiet Djomeni ◽  
Frida Longo ◽  
Pierre Kamtchouing

<p><strong>Methodology:</strong> Wistar rats were randomly assigned into eight groups of five animals each: four male groups and four female groups. Each sex group had a control group receiving distilled water and three test groups receiving 200, 500 and 1000mg/kg respectively. Animal’s body weights were recorded on the first day and once a week for the four experiment weeks. The hematological analysis included total WBC count, total RBC count, Hb, %HCT, MCV, MCH and MCHC. Biochemical/serum profile studies include TG, TC, ALT, AST, urea and TP. Tissue specimens of the liver, kidney and lung were subjected to histological examination using standard hematoxylin-eosin staining.</p><p><strong>Results:</strong> In male rats, aqueous extract showed significant decreases in relative weight of liver with extreme significance P&lt;0.001 at a dose of 200mg/kg (vs. control group), P&lt;0.001 of lung at all the doses, P&lt;0.05 (200 and 500mg/kg) and P&lt;0.01 (1000mg/kg) in heart weight. In relative kidney weight, only the dose of 1000mg/kg showed a significant increase vs. normal control male rats. Unlike male rats, only relative kidney weight in female rats was significantly different from the control group in a dose-dependent manner. The aqueous extract treated male groups showed significant increases P&lt;0.001 (1000mg/kg) of total WBC count and MCHC, significant decreases of %HTC (dose response manner), P&lt;0.05 total RBC count (at doses of 500 and 1000mg/kg) and Hb P&lt;0.01 (500mg/kg) vs. normal male rats. In female rats, the haematological study showed significant increase P&lt;0.01 of total WBC count (at the doses of 500 and 1000mg/kg), significant decreases P&lt;0.05 and P&lt;0.01 of total RBC respectively at the doses of 200 and 1000mg/kg, significant decrease of Hb with extreme significance P&lt;0.001 at the dose 1000mg/kg, %HTC also decrease dose response manner vs. control female rats. Biochemical study showed in male rats significant decreases in level of TG P&lt;0.001 (at the doses of 200 and 500mg/kg) and urea, although it showed any dose-dependent effect vs. control male rats. AST also decreases (P&lt;0.05) in male rats at the dose of 200mg/kg but significantly increase P&lt;0.001 at the dose of 500mg/kg. In the female rats, biochemical study revealed significant increases in level of TG P&lt;0.001 and urea P&lt;0.01 at the dose of 200mg/kg and significant decreases in level of TG P&lt;0.01, AST P&lt;0.05 and urea P&lt;0.05 at the dose of 500mg/kg (vs. control female rats). Microscopically, there were mild hepatic and renal tissue injuries supporting the hematological analysis.</p><p><strong>Conclusion:</strong> The results indicated that aqueous extract of <em>Alstonia boonei</em> De Wild is toxic in high doses.</p>


2020 ◽  
Vol 32 (10) ◽  
pp. 914
Author(s):  
M. S. Garcia ◽  
W. A. Orcini ◽  
R. L. Peruquetti ◽  
J. E. Perobelli

This study investigated the reproductive toxicity of methylmercury (MeHg) and Aroclor (Sigma-Aldrich), alone or in combination, following exposure of prepubertal male rats considering the chromatoid body (CB) as a potential target. The CB is an important molecular regulator of mammalian spermatogenesis, primarily during spermatid cytodifferentiation. Male Wistar rats were exposed to MeHg and/or Aroclor , according the following experimental design: control group, which was administered in corn oil (vehicle) only; MeHg-treated group, which was administered 0.5mg kg−1 day−1 MeHg; Aroclor-treated group, which was administered 1mg kg−1 day−1 Aroclor; Mix-LD, group which was administered a low-dose mixture of MeHg (0.05mg kg−1 day−1) and Aroclor (0.1mg kg−1 day−1); and Mix-HD group, which was administered a high-dose mixture of MeHg (0.5mg kg−1 day−1) and Aroclor (1.0mg kg−1 day−1). MeHg was diluted in distilled water and Aroclor was made up in corn oil (volume 1mL kg−1). Rats were administered the different treatments from PND23 to PND53 by gavage, . The morphophysiology of CBs was analysed, together with aspects of steroid hormones status and regulation, just after the last treatment on PND53. In addition, the long-term effects on sperm parameters were assessed in adult animals. MeHg exposure increased mouse VASA homologue (MVH) protein levels in seminiferous tubules, possibly affecting the epigenetic status of germ cells. Aroclor produced morphological changes to CB assembly, which may explain the observed morphological defects to the sperm flagellum and the consequent decrease in sperm motility. There were no clear additive or synergistic effects between MeHg and Aroclor when administered in combination. In conclusion, this study demonstrates that MeHg and Aroclor have independent deleterious effects on the developing testis, causing molecular and morphological changes in CBs. To the best of our knowledge, this is the first study to show that CBs are targets for toxic agents.


Author(s):  
S Sakila ◽  
N Begum ◽  
S Kawsar ◽  
ZA Begum ◽  
MS Zola

Aims: This study was aimed to find out anti-fertility effects of Andrographis paniculata (AP) plant. Study design & Methodology: A prospective case control animal study with 85 female and 30 male rats (Total 115 rats) was done in the Department of Pharmacology of Dhaka Medical College and Bangladesh Medical College, Dhaka, Bangladesh from July 2002 to December 2003. The total 85 female rats were grouped into case study or exposure group (N=60 female rats) exposed to water extract of AP & control or non exposure group (N=25 female rats, 30 male rats also considered as control group) Exposure group (water extract) of female were again subdivided in 3 groups according to duration of (A.P) exposure (N=20 in each group) e.g. 4 weeks, 6 weeks and 8 weeks. Mating schedules were done after the completion of scheduled duration of exposure with A.P (Dose was 1 gm/kg). Results: In group I percentage of infertility was 33.33% in 4 weeks exposure, 50% in 6 weeks exposure & 100% in 8 weeks exposure respectively. In control group (Group II) percentage of infertility was 0%. In case study group of female rats the value of FSH was 1.20 1U/L (4 weeks), 1.12 1U/L (6 weeks), 1.00 1U/L (8 weeks), LH 0.78 1U/L (4 weeks), 0.70 1U/L (6 weeks), 0.64 1U/L (8 weeks), Estrogen 45.30 pg/ml (4 weeks), 44.80 pg/ml (6 weeks), 44.20 pg/ml (8 weeks) and Progesterone 4.84 nmol/L (4 weeks), 4.72 nmol/L (6 weeks) and 3.80 nmol/L (8 weeks). In non exposure group the value of FSH was 1.23 1U/L, LH 0.80 1U/L, Estrogen 47.05 pg/L and Progesterone 5.50 nmol/L. In exposure group all the values were lesser than the normal hormonal value. Conclusion: This study suggests that due to lower level of hormone, female rats have promising percentage of infertility with AP. Further study is needed with rat as well as clinical trial with human being. Key Words: Andrographis paniculata, Antifertility effects doi: 10.3329/bjms.v8i1.3183 Bangladesh Journal of Medical Science Vol.8 No. 1-2; 2009 10-14


2011 ◽  
Vol 282-283 ◽  
pp. 195-200
Author(s):  
Yu Bin Ji ◽  
Jing Chao Sun ◽  
Lang Lang

Solanine is one of chemicalcomponents in the tuber and the sprout of the potato which is toxic to human. Some studies on the toxicity of solanine on humans and animals have been reported, little is known about the mechanism of its testicular toxicity. In present study, the toxicity of solanine on male reproductive function was investigated in adult male Kunming mice. Compared with the control group, there was an obvious pathological change in testis, and the expression levels of 3β-HSD and vimentin decreased when the test concentration of solanine was at 21 mg/kg/day. Meanwhile, there was a significant dose- and duration-dependent reduction in the testicular weight and organ coefficient. However, no changes have been detected about the level of testosterone and there was a dramatic increase in the expression of LH in Leydig cells. Results of this study suggested that solanine leaded to male reproductive toxicity influencing the functions of Sertoli cells and Leydig cells.


1961 ◽  
Vol 36 (4) ◽  
pp. 485-497 ◽  
Author(s):  
G. P. van Rees

ABSTRACT The hypothesis that steroid sex hormones influence pituitary F. S. H. by independent actions on its production and capacity of the gland to release it has been investigated by means of incubation experiments. During incubation, rat pituitary glands released considerable amounts of F. S. H. into the medium. Inactivation of F. S. H. during incubation could not be demonstrated; once (in females) some production of F. S. H. was even observed. The amount of F. S. H. which is released into the medium is influenced by the quantity of F. S. H. stored in the hypophyses. Hypophyses from male rats pretreated with oestradiol released relatively more F. S. H. into the medium than hypophyses from control animals. On the other hand, pretreatment with testosterone caused the pituitary glands to release less F. S. H. into the medium. In agreement with these results, hypophyses from intact male rats released relatively less F. S. H. than hypophyses from intact female rats. These facts support the hypothesis that androgens depress pituitary F. S. H.-secretion by inhibiting the capacity to release it, while oestrogens, which can even promote this property of the pituitary gland, also act by directly inhibiting its production.


2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Neena Singla ◽  
Swati Challana

The aim of study was to investigate the toxic effect of triptolide fed in bait on reproduction of male house rat,Rattus rattus. Feeding of cereal based bait containing 0.2% triptolide to maleR. rattusfor 5 days in no-choice feeding test, leading to mean daily ingestion of 20.45 mg/kg bw of triptolide, was found effective in significantly(P≤0.05)reducing sperm motility and viability in cauda epididymal fluid by 80.65 and 75.14%, respectively, from that of untreated rats. Pregnancy rates were decreased by 100% in untreated cyclic female rats paired with male rats treated with 0.2% triptolide. Present studies suggest the potential of 0.2% triptolide bait in regulating reproductive output ofR. rattus.


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