scholarly journals Repeated-Dose Toxicity Testing of Scolopendrid Pharmacopuncture in Sprague-Dawley Rats

2020 ◽  
Vol 37 (2) ◽  
pp. 110-117
Author(s):  
Jongwon Jang ◽  
Wookcheol Seo ◽  
Hongmin Chu ◽  
Kyungtae Park ◽  
SunKyung Kim ◽  
...  

Background: The aim of this pilot study was to assess the safety and dosing of scolopendrid pharmacopuncture (SPP).Methods: A total of 40 healthy Sprague-Dawley rats (males and 20 females 20) were selected following a 7-day inspection and acclimation period. SPP was administered via intramuscular injection, over a 2-week period using 3 doses including a high-dose [0.84 mg of scolopendrid per kg of body weight (BW)], a meddose (0.42 mg/kg BW), and a low-dose (0.21 mg/kg BW). The control group was injected with sterile water into the muscles. Unusual changes caused by administration of the test substance were observed. Weight, feed intake, organ weight, and hematological examinations were compared among the groups. Using the SPSS statistical program, Levene’s test was performed to evaluate the homogeneity of variances, and a one-way ANOVA test was subsequently performed to assess the significance between each test group.Results: During the experiment no animals died. Weight change, food consumption, organ weight, hematological test, and blood biochemical tests showed no significant differences in the treatment groups compared to controls.<br>Conclusion: No toxicological changes related to the administration of test substances were observed. Therefore, the LD<sub>50</sub> (lethal-dose that kills 50%) of scolopendrid pharmacoupuncture in rats was greater than 0.84 mg/kg.

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Kyungjin Lee ◽  
Ho-Young Choi

Studies on the safety of herbal medicine are essential for the development of new drugs. The aim of this study was to evaluate the no-observed-adverse-effect-level (NOAEL) of HVC1 (Gamisamhwangsasim-tang, a 30% ethanol extract of a mixture of Pruni Cortex, Scutellariae Radix, Coptidis Rhizoma, and Rhei Rhizoma) and identify its target organs after oral administration to Sprague-Dawley (SD) rats repeatedly for 13 weeks. Three test groups were treated with HVC1 at a dose of either 500 (low-dose), 1,000 (middle-dose), or 2,000 (high-dose) mg/kg/day. Another group received high-dose HVC1 and was observed for 4 weeks following treatment to examine recovery from the effects of the extract. All treatment groups were compared to a vehicle control group. During the study, mortality, clinical signs, body weight changes, food consumption, abnormal lesions in the eye, urinary parameters, hematological parameters, blood coagulation time, blood biochemical parameters, changes in organ weight, gross findings, and histopathological changes were examined. No systemic toxicity related to HVC1 was observed in any group, and it was concluded that the NOAEL of HVC1 was 2,000 mg/kg/day. No target organ was identified.


2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Ji Hyun Lee ◽  
Mary Gulumian ◽  
Elaine M. Faustman ◽  
Tomomi Workman ◽  
KiSoo Jeon ◽  
...  

Background. To investigate the effect of subacute intravenous administration AgNP (silver nanoparticles, 10 nm) and AuNP (gold nanoparticles, 12.8 nm) and AgNP/AuNP mixture to blood biochemistry, hematology, and platelet coagulation, subacute toxicity study was conducted. Methods. AuNP and AgNP in which their size distribution was not statistically different, mixed or separate, were injected into the caudal vein of male Sprague-Dawley rats for 4 weeks. The rats were allowed to recover for a further 4 weeks in order to examine systemic toxicity expressed in the blood biochemistry and hematology. The dose groups (5 males per group for the administration and 3 males for the recovery) consisted of 7 divisions, i.e., control, AgNP (with a low dose of 10 μg/kg/day and a high dose of 100 μg/kg/day), AuNP (with a low dose of 10 μg/kg/day and a high dose of 100 μg/kg/day), and mixed AgNP/AuNP (with a low dose of 10/10 μg/kg/day and a high dose of 100/100 μg/kg/day). Results. There were no significant dose-related changes in the hematology and blood biochemical values for the rats. Coagulation time in terms of the active partial thromboplastin time (APTT) and prothrombin time (PT) did not show any significant changes, when compared to the control group. Conclusion. The subacute injection of AuNP and AgNP or their mixture did not induce any noticeable systemic toxicity.


2020 ◽  
Vol 4 ◽  
pp. 239784732091321
Author(s):  
Manish Jain ◽  
Moninder Kaur ◽  
Deepika Pandey Tiwari ◽  
Chandrashekara Vishwanath ◽  
Nataraju Javaregowda ◽  
...  

Gossence™ (galactooligosaccharide; GOS) is a prebiotics and used as one of the major constituents in infant milk formulas that act as a functional food. Gossence is manufactured by Tata Chemicals Ltd, India, through a patented process of biotransformation of lactose. A toxicology study in juvenile rats was carried out to assess the safety profile of Gossence intended for pediatric population. The objective of this study is to assess the potential systemic toxicity of Gossence when administered through gavage at dose levels of 1000, 2000, or 5000/3000 mg/kg/day (equivalent to 1347, 2694, and 6735/4041 mg/kg/day of GOS, respectively) to juvenile Sprague Dawley rats from postnatal day (PND) 4 to PND 52 (i.e. total 49 days of dosing period). A separate group of animals were treated with vehicle (purified Milli Q water) for a similar duration. The following parameters were evaluated during the study period: morbidity/mortality check, clinical signs, body weights, body weight changes, food consumption, functional observational battery, motor activity, postnatal developmental observations, hematology, clinical chemistry, urinalysis, organ weight, gross pathology, and histopathology. During dosing phase, the high-dose group, 5000 mg/kg/day, was reduced to 3000 mg/kg/day (equivalent to 4041 mg/kg/day dose of GOS) from day 16 (PND 19) onward, due to clinical signs of watery feces and yellow color stains at urogenital region and mortality in two animals on day 15 (PND 18) of the study. Time-weighted average dose for 5000 mg/kg/day was equivalent to 3600 mg/kg/day. No further deaths or clinical signs were noticed in animals at 3000 mg/kg/day from day 18 (PND 21) of dosing phase to until terminal euthanization. At the terminal euthanization, there were no test item-related gross changes observed in all surviving rats except for, an increased cecum size in some of the rats at 5000/3000 mg/kg/day, which correlated with the increased weights of cecum with contents during organ weight recording, but this had no correlating light microscopic changes during histological examination. The cecal enlargement was completely recovered following the 14-day recovery period. The no-observedadverse-effect level is 3000 mg/kg/day for Gossence, which is equivalent to 4041 mg/kg/day of GOS in both sexes.


2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Xing Zhou ◽  
Guo-Wei Zhang ◽  
Wei-Ning Liang ◽  
Yi-Ze Li ◽  
Song Xu ◽  
...  

To investigate the effect and mechanism of action of Moriamin Forte (MF) on oligoasthenospermia (OA) in rats exposed to multiglycosides of Tripterygium wilfordii (GTW), forty male Sprague Dawley rats were randomly divided into four groups. Rats in the control group were treated with 0.5% sodium carboxymethyl cellulose. The remaining rats were administered GTW (30 mg/kg/d) for 40 d to establish an OA model. Concurrently, the groups were treated with normal saline and low-dose (100 mg/kg/d) and high-dose (200 mg/kg/d) MF, respectively. After treatment, the number and motility of sperm cells were examined. Testicular and epididymal histomorphology changes were observed. Antioxidant indicators (SOD, CAT, MDA, TAC, and Nrf2) in testicular and epididymal tissues were detected. Apoptotic and antiapoptotic indicators (Bax and Bcl2 expression) in the testicular tissue were measured by immunohistochemistry. GTW decreased sperm count and motility, damaged testicular and epididymis tissues, impaired antioxidase activity, and increased tissue MDA levels. Meanwhile, GTW upregulated the expression of Bax and downregulated the expression of Bcl2. Western blot analysis demonstrated a decrease in the Nrf2 expression in the model group. Treatment with MF improved sperm count and motility, as well as inhibited the rate of apoptosis in the rat reproductive system. Moreover, MF improved the activity of antioxidants and increased the relative expression of the antioxidant pathway-related protein Nrf2. In conclusion, MF may reverse the GTW-induced OA by modulating the expression of apoptotic and antioxidant pathway-related proteins. This study may provide a pharmacological foundation for the use of MF in OA treatment.


2000 ◽  
Vol 19 (4) ◽  
pp. 243-255 ◽  
Author(s):  
R. Henrich ◽  
B. M. Ryan ◽  
R. Selby ◽  
S. Garthwaite ◽  
R. Morrissey ◽  
...  

Fyrolflex resorcinol bis-diphenylphosphate (RDP) was evaluated in a two-generation reproductive study as part of a program to assess the overall toxicology of this flame retardant. RDP was administered to male and female Sprague-Dawley rats in the diet at concentrations of 1000, 10,000 or 20,000 ppm. The control group was given diet alone. Parental (P1) animals were treated for 10 weeks prior to mating, during the 2-week mating period, throughout gestation, and through lactation until sacrifice. The F1 generation (P1 offspring) was treated following a regimen similar to P1. The F2 generation was not treated. No significant difference in Utter survival was observed between the control and treated groups. Body weights were significantly decreased in P1 rats during the 1st week due to an initial flavor aversion of the test substance in the diet. Body weight, weight gains, and food consumption were decreased in the test substance-treated pups (F1) during lactationand after weaning. These changes were also attributed to a flavor aversion. Anogenital distance was similar in the control and high-dose groups, whereas vaginal opening and preputial separation were delayed in the 10,000 and 20,000 ppm groups, and were considered to be secondary to the reduction in F1 body weight. Neither parents nor offspring exhibited any test substance-related clinical signs of toxicity. Vaginal cytology and cyclicity and male reproductive functions (sperm count, motility, and morphology) were unaffected by treatment. Mating performance was similar in the treated groups relative to the control. No treatment-related lesions were noted in the reproductive organs. Increased liver weight and associated hepatic periportal hypertrophy were observed in the RDP-treated animals (P1 and F1). In conclusion, there were no adverse effects on reproductive performance or fertility parameters associated with RDP administration in the diet. Fyrolflex RDP administered for greater than 13 weeks and up to the entire life span (i.e., F1, from conception to euthanasia) resulted in increased liver weights with associated periportal hypertrophy. This change was considered an adaptive process associated with RDP metabolism in the liver.


2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Satish Jankie ◽  
Jenelle Johnson ◽  
Amusa Sarafadeen Adebayo ◽  
Gopal Krishna Pillai ◽  
Lexley Maureen Pinto Pereira

This study examined the effectiveness of niosomes loaded with levofloxacin in treating Pseudomonas aeruginosa (American Type Culture Collection—ATCC 27853) infections in Sprague Dawley rats since these infections are becoming more common and resistant to treatment. Levofloxacin entrapped in niosomes was prepared using the thin-film hydration method and was assessed for in vitro release and stability. Three groups of six (6) animals were infected with a lethal dose of Pseudomonas aeruginosa via the intraperitoneal (Ip) route. At six (6) hours postinfection, the animals were treated with either drug-free niosomes (control), free levofloxacin (conventional), or levofloxacin trapped in niosomes (Ip) at a dose of 7.5 mg/kg/once daily. Blood was collected via tail snips on days 0, 1, 3, 5, 7, and 10 for complete blood counts and viable bacterial counts (CFU/μl). At day 10, the animals were sacrificed, and the kidney, liver, and spleen were harvested for bacterial counts. The niosomes showed a sustained drug release profile and were most stable at 4°C. All animals in the control group succumbed to the infection; one animal from the conventional group died, and all niosome treated animals survived at day 10. The mean lymphocyte count (×109) was lower for the niosome (7.258 ± 1.773) versus conventional group (17.684 ± 10.008) ( p < 0.03 ) at day ten (10). Neutrophil counts (×109) were lower for the niosome (2.563 ± 1.609) versus conventional (6.2 ± 6.548) ( p < 0.02 ) groups. Though CFUs in the bloodstream were comparable for both treatment groups, the niosome treated group showed a significant reduction of CFUs in the liver, kidney, and spleen versus the conventional group (1.33 ± 2.074) vs (5.8 ± 3.74) ( p < 0.043 ), (1.5 ± 2.35) vs (9.6 ± 8.65) ( p < 0.038 ) and (3.8 4.71) vs (25.6 14.66) ( p < 0.007 ), respectively. These findings indicate that niosome is promising as a drug delivery system in treating systemic infections, but further work using niosomes with surface modification is recommended.


2010 ◽  
Vol 30 (7) ◽  
pp. 786-790 ◽  
Author(s):  
Minfen Yan ◽  
Gaoren Zhong ◽  
Linfeng Gao ◽  
Xiqiao Xia ◽  
Lihua Wang ◽  
...  

This study was designed to evaluate the effects of depleted uranium (DU) on 1α-hydroxylase in the kidney of rats and to delinerate the mechanism of damage to kidneys and bones by DU. Male Sprague-Dawley rats were surgically implanted with DU fragments at three dose levels (0.1 g, 0.2 g and 0.3 g). After 3, 6 or 12 months, the concentration of 1α,25(OH)2D3 in the kidney was measured by radioimmunoassay. The activity of 1α-hydroxylase was shown by the production of 1α,25(OH)2D3 after incubation. The results showed that the 1α-hydroxylase activity in the kidney was decreased after 3 months (27.2% at the medium dose DU group, p < 0.05; 33.4% at the high dose DU group, p < 0.01). In contrast, at 6 months and 12 months after implantation of DU, the activity of renal 1α-hydroxylase in DU-treated animals was not decreased significantly in comparison with the controls (p > 0.05). On the other hand, the activity of renal 1α-hydroxylase was decreased by 33.1% (p < 0.05) and 34.4% (p < 0.01) in blank control groups at 6 and 12 months, respectively, when compared with the blank control group at 3 months. In conclusion, this study showed that chronic DU exposure could induce renal damages and inhibit the synthesis of biologically active form of vitamin D, which may be the underlying mechanism of bone metabolic disorder caused by renal injury after DU exposure.


Author(s):  
O. H. Ayoade ◽  
G. G. Akunna ◽  
F. I. Duru

This study evaluated camphora-induced androgenic and histopathological changes in male Sprague-Dawley rats. Thirty-five animals weighing 200 g±20 g were used for this study and randomly divided equally into five groups, with seven rats in each group. Group A animals (normal control group) were served water and rat chow only; Groups B-D (treatment groups) were orally administered camphora in doses of 1 g/kg (Low-dose), 2 g/kg (Medium-dose) and 4 g/kg (High-dose) respectively while Group E (vehicle group) were orally administered 6 mL/kg olive oil (a solvent for camphora) per day for 56 days. There was a significant decrease (P< .05) in activity levels of Follicle-Stimulating Hormone (FSH); Superoxide Dismutase (SOD) when the treatment was compared with the control group. Also, a significant decrease (P< .05) in activity level of FSH was observed when the Medium-dose group was compared with Low-dose group. Insignificant irregular pattern in activity level of Testosterone was observed across the treatment groups when compared with the control. However, a significant increase (P< .05) in activity level of Testosterone was observed when the High-dose group was compared with the Medium-dose group. There was a significant increase (P< .05) in activity levels of Luteinizing Hormone (LH) and Malondialdehyde (MDA) when the treatment was compared with the control group. Semen analysis showed reduction in sperm concentration, motility and morphology with increasing concentration of camphora. Significant decrease was recorded in testicular weight when High-dose group was compared to Control and Low-dose groups. Histopathological changes were seen in the testes of the camphor administered groups, ranging from mild disintegrated interstitial tissues in Low-dose to severe degeneration and disintegration of both seminiferous and interstitial tissues in the testes in the Medium-dose and High-dose groups. In conclusion, camphora had androgenic and toxic effects on testis and may cause testicular tissue damage.


2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Dai Yan-Ping ◽  
Gao Xiao-Qin ◽  
Ma Xiao Ping ◽  
Yue Ying Quan

Objective. To study the expressions of VEGF and VEGFR2 at protein level in the epididymis of rats with arsenism. Methods. Forty male Sprague-Dawley rats were randomly divided into four groups: the high dose arsenic infected group (60.0 mg/L in water), the middle dose arsenic infected group (12.0 mg/L in water), the low dose arsenic infected group (2.4 mg/L in water), and the control group (distilled water). Rats were treated with arsenic through drinking water for 6 consecutive months. At the end of the experiment, the average densitometry values of apoptotic cells in epididymis tubules were determined by TUNEL method; the protein and mRNA levels of VEGF and VEGFR2 were observed by immunohistochemistry, Western blot, and real time fluorescent quantitative PCR, respectively. Results. Compared with the control group, in each infected group, the average densitometry values of apoptotic cells in the epididymis tubules were significantly lower. Compared with control group, protein and mRNA levels of VEGF and VEGFR2 in each infected group were obviously declined. The correlations between protein and mRNA levels of VEGF and VEGFR2 were positively exhibited (r = 0.843, 0.869, p < 0.05). Conclusions. Arsenism affects the expressions of VEGF and VEGFR2 in the epididymis of rats and results in apoptosis of pathophysiology of male infertility.


2020 ◽  
Vol 18 ◽  
pp. 205873922093566
Author(s):  
Liqin Wei ◽  
Jitao Wu ◽  
Danxia Li ◽  
Zhengfei Shan

Ketamine abusing is associated with ulcerative cystitis, but the mechanisms remain unclear. This study aimed to investigate the existence of ketamine-induced symptom in a rat model and evaluate the underlining mechanisms. Sprague-Dawley rats were chosen and randomly divided into 12 groups (n = 8), such as the control group, low dose of ketamine (10 mg/kg/day), middle dose of ketamine (30 mg/kg/day) and high dose of ketamine (50 mg/kg/day) groups. The experimental groups were administrated ketamine i.p. daily, whereas the control groups were administrated with saline. After 1, 3, and 6 months of treatment, the bladder tissues were collected. Haematoxylin and eosin (HE) staining and a transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay were used to evaluate the bladder epithelium pathology and urothelial apoptosis, respectively. The protein expression levels of LC3, p62, Beclin1 were assessed by Western blotting. HE staining results of the experimental rats showed the bladder tissue denudation of the urothelial epithelium with edema and congestion compared with the control groups. TUNEL staining showed a significantly higher number of apoptotic cells in experimental groups than in the control groups. The protein LC3 and Beclin1 had significantly higher levels compared with control groups. The protein p62 had lower levels compared with control groups. The expression levels correlated with contraction of ketamine and treatment time. HE staining, TUNEL staining and Western blot results showed dose-dependent, time-dependent autophage in ketamine-treated rats. All the results suggested that autophagy proteins might be involved in inflammatory response in rats.


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