scholarly journals 14-Day Repeated Intraperitoneal Toxicity Test of Ivermectin Microemulsion Injection in Wistar Rats

2020 ◽  
Vol 7 ◽  
Author(s):  
Zhen Dong ◽  
Shou-ye Xing ◽  
Ji-yu Zhang ◽  
Xu-zheng Zhou
Keyword(s):  
Toxicity Test ◽  
Wistar Rats ◽  
Histopathological Examination ◽  
Clinical Chemistry ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Toxic Injury ◽  
Male And Female Rats ◽  
Initial Stage

To evaluate the safety of ivermectin microemulsion injection, 100 Wistar rats were injected intraperitoneally at 0.38 g/kg, 0.19 g/kg, and 0.1 g/kg for 14 days. The 14-day repeated toxicity test of ivermectin microemulsion injection was systematically evaluated by clinical observation, organ coefficient, hematological examination, clinical chemistry examination, and histopathological examination. The results showed that no rats died during the test. At the initial stage of treatment, the rats in the high dose group had mild clinical reaction, which disappeared after 4 days. Clinical chemistry showed that the high dose of ivermectin microemulsion could cause significant changes in ALT and LDH parameters in male rats; high and medium doses could increase the liver coefficients of male and female rats. The toxic target organ may be the liver as indicated by histopathological findings. No significant toxic injury was found in the heart, liver, spleen, lung, kidney, brain, ovary, and testes of all groups of rats. No drug-related toxic effects were found at low doses, and thus the NOVEL of ivermectin microemulsion injection was 0.19 g/kg.

Studies of the Toxicological Potential of Tripeptides (L-Valyl-L-prolyl-L-proline and L-lsoleucyl-L-prolyl-L-proline): IV. Assessment of the Repeated-Dose Toxicological Potential of Synthesized L-Valyl-L-prolyl-L-proline in Male and Female Rats and Dogs

2005 ◽  
Vol 24 (4_suppl) ◽  
pp. 25-39 ◽  
Author(s):  
Yasunori Nakamura ◽  
Izuki Bando ◽  
John H. Mennear ◽  
Bruce K. Bernard
Keyword(s):  
Body Weight ◽  
Clinical Chemistry ◽  
Clinical Pathology ◽  
Female Rats ◽  
Male Rats ◽  
Repeated Dose ◽  
High Dose ◽  
Male And Female ◽  
Organ Weights ◽  
Male And Female Rats

The objective of these repeated-dose, 8-week studies was to assess the toxicological potential of a synthetic tripeptide, L-valyl-L-prolyl-L-proline (VPP), when administered to Charles River rats and Beagle dogs. Groups of 20 male and 20 female rats were fed powdered diets containing sufficient VPP to afford daily doses of 0, 2, 8, or 16 mg/kg body weight (BW)/day. Groups of five male and five female dogs were administered 0, 2, 8, or 16 mg/kg BW/day in hard gelatin capsules. Antemortem evaluative parameters for both species included grossly observable clinical signs, body weight and food consumption, clinical pathology (hematology, clinical chemistry, urinalysis), and ophthalmological examinations. Dogs also received electrocardiographic examinations. Postmortem evaluations in both species included complete necropsy, determination of major organ weights, and histopathological examination of specimens from approximately 50 organs and tissues. All rats and dogs survived to the scheduled termination of the studies and neither species exhibited evidence of VPP effects on appetite or body weight gain/maintenance. Ophthalmic examinations revealed occasional lens clouding in rats, but this occurred in all groups and was not attributable to VPP. Some clinical pathology parameters in both species were occasionally altered, but there was no evidence that this was dose-related. Electrocardiographic examinations in dogs revealed no VPP-associated changes. Mid- and high-dose male rats (but not females) had slightly reduced mean pituitary and kidney weight parameters, whereas mid- and high-dose females had slightly increased mean uterus:body weight ratios. There were no microscopic correlates for these minor changes. Ten percent to 20 % of all female rats (but not males) exhibited corticomedullary mineralization of the kidney and gliosis of the optic nerve, and 10% to 20% of males (but not females) had thymic hemorrhage. Postmortem evaluations of dogs revealed no VPP-related effects on organ weights or either macro- or microscopic appearances of organs. The results of these studies provided no evidence of either local or systemic toxicity. Similarly, there was no evidence of neurotoxicity that might have been detected by the appearance of physical or behavioral changes during gross observations of animals. Although these results do not identify target organs for VPP toxicity, the no-observable-effect level and maximally tolerated dose are both greater than 16 mg/kg/day when administered to male and female rats and dogs for 8 consecutive weeks. Based upon food enhancement levels of VPP currently being evaluated, the resultant margin of safety (160) is substantial.

scholarly journals Subacute Toxicity Profile of Lacidipine Nanoformulation in Wistar Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Rupesh Shirodkar ◽  
Chandrasekhar Misra ◽  
Chethan GH ◽  
Pallavi Shetty ◽  
Zenab Attari ◽  
...  
Keyword(s):  
Body Weight ◽  
Wistar Rats ◽  
The Body ◽  
Female Rats ◽  
Male Rats ◽  
Control Group ◽  
High Dose ◽  
Testis Weight ◽  
Delayed Effect ◽  
Male And Female Rats

The present study was aimed at investigating the safety of Lacidipine (LCDP) loaded nanostructured lipid carriers (NLCs) in Wistar rats. NLCs were formulated using ultrasound dispersion technique. Animals were orally treated once daily with NLCs containing 0.140 mg, 0.350 mg, and 0.875 mg of LCDP as low, medium, and high dose per kg body weight, respectively, during 28 days along with blank formulation and pure LCDP. Control rats were fed with water. Animals were observed throughout experiment period and their body weight was recorded once weekly. Overnight fasted rats were sacrificed on the 29th day. Study revealed no signs or symptoms of toxicity or morbidity. No significant changes in the body weight were observed between treated and control group. Significant increase in left testis weight and liver weight was observed in male and female rats, respectively. Haematological estimation revealed significant decrease in haemoglobin count in male rats while female rats showed significant increase in granulocyte count. All the serum clinical parameters were within the normal range and no gross histopathological changes were observed. No delayed effect was noted in satellite group. The results indicate that developed LCDP loaded NLCs are safe when administered orally in rats.

scholarly journals Coronary Artery and Myocardium Injuries Induced by a High Cholesterol and Fructose Diet in Growing Male and Female Wistar Rats

2021 ◽  
Vol 78 (2) ◽  
pp. 1
Author(s):  
Lynda AÏNOUZ ◽  
Mohamed ZAOUANI ◽  
Hayat REMICHI ◽  
Sofiane BOUDJELLABA ◽  
Kahina CHABANE ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Wistar Rats ◽  
Histopathological Examination ◽  
Female Rats ◽  
Male Rats ◽  
Standard Diet ◽  
High Cholesterol ◽  
Male And Female ◽  
Male And Female Rats ◽  
Female Wistar Rats

Cardiovascular disease (CVD) are mainly consequent of atherosclerosis.  Men develop CVD at a young age, this risk increases in women at an older age. Several studies have been carried out on male rats, but experiments on growing rats especially female are rare.  The objective of this study was to investigate the effect of a high cholesterol and high fructose diet on the coronary artery and myocardium in growing male and female rats Young Wistar rats were divided into control groups fed a standard diet, cholesterol groups supplemented with 3% cholesterol (ChD), and cholesterol-fructose groups supplemented with 3% cholesterol and 15% fructose (ChFrD) for 14 weeks. Each group consists of male (n=6) and female (n=6) rats.   We found, in comparison with corresponding controls rats, that both ChD and ChFrD diets caused a significant hyperglycemia and dyslipidaemia. In hearts supernatants, we highlighted increases of total lipids, malondialdehyde and Catalase assays. The histopathological examination showed a disorganization of the myocardial structure, arterial walls damage and endothelium injuries. Our study showed that ChD and ChFrD diets, caused weight, biochemical, oxidative and tissue disturbances that could lead to CVD in both young male and female Wistar rats even during the growing period.

scholarly journals Biochemical effects of Short–long Term Extensive Administration of Monosodium Glutamate and Soybean on Wistar Rats

2021 ◽  
pp. 14-27
Author(s):  
A. Bob-Chile Agada ◽  
N. Nwachukwu ◽  
C. O. Ibegbulem ◽  
A. C. Ene
Keyword(s):  
Blood Glucose ◽  
Wistar Rats ◽  
Total Bilirubin ◽  
Monosodium Glutamate ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Male And Female ◽  
Male And Female Rats ◽  
Excessive Consumption

This study was carried out to investigate the effect of prolonged and excessive consumption of soybean and monosodium glutamate on blood glucose, insulin, and liver function. The quantitative and qualitative determination of oestrogen-like compounds was carried out by chromatography. A total of two hundred and ten (210) Wistar rats (70 – 78g) were divided equally into three groups representing the various experimental durations (2, 4, and 6 months). Each of these groups was further sub-divided equally into fourteen (14) subgroups (7 groups for male rats and 7 groups for female rats). Out of the 7 groups for both the male and female rats, a group represented the control rats only fed commercial rat chow and water, whereas the rest were orally administered any of the 1000 mg/kg b.w (low dose), 2000 mg/kg b.w (medium dose), or 3000 mg/kg b.w (high dose) of aqueous extract of monosodium glutamate or soybean. Diadezein (42.63 mg/100g), and genistein (28.49 mg/100g) were the two most abundant oestrogen-like compounds. After 6 months administration the high dose (H.D) MSG and soybean, significantly altered the blood glucose and insulin levels of both the male and female rats. The liver enzymes levels of the female rats were significantly elevated after 2 months of administration of H.D MSG and soybeans. All the doses of soybean administered for 6 months significantly elevated the liver enzyme levels compared to the control. The administration of H.D MSG for 4 and 6 months significantly increased the total bilirubin levels of female rats while no significant changes were observed following soybeans administration. For the male rats, no significant changes were observed on the total bilirubin levels after the administration soybeans, whereas H.D MSG for 2 months significantly increased the total bilirubin levels (12.00 µmol/l) compared to the control (8.60 µmol/l). This study has shown that regardless of the presence of medicinal compounds in soybeans, excessive prolonged intake compromises the functional integrity of the liver while MSG even at minimal doses poses serious health risks.

scholarly journals Acute and sub-acute oral toxicity of aqueous whole leaf and green rind extracts of Aloe vera in Wistar rats

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Florence Nalimu ◽  
Joseph Oloro ◽  
Emanuel L. Peter ◽  
Patrick Engeu Ogwang
Keyword(s):  
Toxicity Test ◽  
Wistar Rats ◽  
Leaf Extract ◽  
Aloe Vera ◽  
Female Rats ◽  
Male Rats ◽  
Aqueous Extracts ◽  
Acute Oral Toxicity ◽  
Oral Toxicity ◽  
Leaf Extracts

Abstract Background Several local communities in Central, Western, Eastern, and Northern regions of Uganda have been using the whole leaf extracts of Aloe vera (L.) Burm. f. (Asphodelaceae) in the treatment of various ailments. Also, several commercial companies sell A. vera as soft drinks in Uganda. However, there are inadequate reports on the toxicities of such preparations. This paper reports the acute and sub-acute oral toxicity of aqueous extracts of whole leaf and green rind of A. vera in Wistar rats. Methods Acute oral toxicity test was carried out in female Wistar rats at doses of 175, 550, 1750, and 5000 mg/kg, p.o. The animals were observed for signs of toxicity for 14 days. Similarly, a sub-acute oral toxicity test was performed in both sexes of rats at doses of 200, 400, and 800 mg/kg, p.o. daily for 28 days. All the groups of animals were monitored for behavioral, morphological, biochemical, and physiological changes, including mortality and compared with respective controls. Body weights were measured weekly while the animals’ relative organ weights, hematological, biochemical, gross, and microscopic pathology were examined on day 29. Results There was no mortality or apparent behavioral changes at the doses tested in acute and sub-acute oral toxicity tests. Thus, the Median Lethal Dose (LD50) of green rind and whole leaf aqueous extracts was above 5000 mg/kg. Gross anatomy revealed that the rats’ relative spleen weight in green rind extract at 200 mg/kg significantly decreased compared to the control group. The creatinine levels in female rats that received green rind extract and the chloride ion levels in male rats administered whole leaf extract were significantly elevated. Conversely, Mean Corpuscular Hemoglobin Concentration (MCHC) levels significantly decreased at lower doses of the green rind extract compared to the control. Histopathology of the kidney revealed the renal interstitium’s inflammation at doses of 200 and 800 mg/kg of the whole leaf extract. Conclusion The findings demonstrated that A. vera green rind and whole leaf extracts are non-toxic at relatively high doses when used for a short duration. Prolonged use of the aqueous whole leaf extract might be associated with kidney toxicity.

Influence of in utero di-n-hexyl phthalate and di-cyclohexyl phthalate exposure on the endocrine glands and T3, T4, and TSH hormone levels of male and female rats: Postnatal outcomes

2020 ◽  
Vol 36 (6) ◽  
pp. 399-416
Author(s):  
Nurhayat Barlas ◽  
Emre Göktekin ◽  
Gözde Karabulut
Keyword(s):  
Pituitary Gland ◽  
Dose Group ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Hormone Levels ◽  
Male And Female Rats ◽  
Endocrine Organs ◽  
Body Weights ◽  
Juvenile Stages

The present study was designed to evaluate the effects of di- n-hexyl phthalate (DHP) and di-cyclohexyl phthalate (DCHP) on endocrine organs in rats. Oil control, 20-, 100-, and 500 mg/kg dose groups were selected and administered to pregnant rats on gestational days 6–19 by oral gavage. The neonatal stages of rats continued until postnatal day 20 and the- juvenile stages of rats continued until postnatal day of 32. The rats were allowed to mature until the neonatal and juvenile stages and there after, they were divided into four groups corresponding to the treatment levels. Body and organ weights were recorded, serum was collected, and thyroid, pancreas, pituitary gland, and adrenal gland were removed. There was a decrease in body weights in the 20- and 500mg/kg DHP and in the 20-mg/kg DCHP dose groups in neonatal male rats. In contrast, for female rats, there was an increase in body weights in the 100-mg/kg DCHP dose group and there was a decrease in body weights in the 500-mg/kg DHP dose group. Body weights were increased at 20 and 500 mg/kg in the DHP-exposed juvenile male rats. Serum thyroid-stimulating hormone (TSH) levels were increased in neonatal male rats, while they were increased in the 100-mg/kg DHP group of neonatal and juvenile female rats. Serum triiodothyronine (T3) levels were increased at the high dose of DHP for neonatal male rats and at the low and high dose levels of DCHP for female rats. Serum thyroxine (T4) levels were increased in neonatal rats for DHP. Also, some histopathological changes were observed in the thyroid, pancreas, adrenal, and pituitary gland. In conclusion, it was shown that DHP and DCHP caused negative effects on T3, T4, and TSH hormone levels.

Investigation of the effects of bisphenol-A exposure on lymphoid system in prenatal stage

2020 ◽  
Vol 36 (7) ◽  
pp. 502-513
Author(s):  
Işil Aydemir ◽  
Caner Özbey ◽  
Oktay Özkan ◽  
Şadiye Kum ◽  
Mehmet İbrahim Tuğlu
Keyword(s):  
Lymph Node ◽  
Bisphenol A ◽  
Tissue Damage ◽  
Corn Oil ◽  
Histopathological Examination ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Organ Function ◽  
Pregnant Rats

Bisphenol-A (BPA) used in the production of plastic materials is a temperature-soluble agent. It also has a steroid hormone-like activity; therefore, it poses a danger to human health. In our study, we aimed to investigate the effects of BPA on lymph node and spleen in male rats exposed to this agent during prenatal stage. The pregnant female rats were divided into four groups: control, sham, low dose (300 µg/kg BPA), and high dose (900 µg/kg BPA). BPA was dissolved in 1 mL of corn oil and administered to the pregnant rats every day during pregnancy. On the 21st and 45th day after the birth, male rats’ lymph node and spleen samples were taken and histopathological examination was performed. Samples were stained with hematoxylin and eosin to determine the general histological appearance, and with CD3 and CD20 immunohistochemically. The results of staining were evaluated by H-score, and statistical analysis was performed. In the samples, BPA applications were not found to cause significant tissue damage. But there was a significant decrease in the immunoreactivities of CD3 and CD20 after BPA applications in both 21st and 45th day samples. After high dose BPA administration, decreased CD3 immunoreactivity was statistically significant. It is thought that BPA does not cause histologically significant tissue damage, but it may impair organ function at cellular level. The investigation of molecules involved in organ function will be useful in revealing the mechanisms that will cause dysfunction.

Studies of the Toxicological Potential of Capsinoids: VIII. A 13-Week Toxicity Study of Commercial-Grade Dihydrocapsiate in Rats

2008 ◽  
Vol 27 (3_suppl) ◽  
pp. 101-118 ◽  
Author(s):  
Eri Watanabe ◽  
Terutaka Kodama ◽  
Takeshi Masuyama ◽  
Shoji Tsubuku ◽  
Akira Otabe ◽  
...  
Keyword(s):  
Food Consumption ◽  
Water Intake ◽  
Clinical Chemistry ◽  
Clinical Signs ◽  
Toxicity Study ◽  
Female Rats ◽  
Male Rats ◽  
High Dose ◽  
Sprague Dawley ◽  
Organ Weights

Dihydrocapsiate, (4-hydroxy-3-methoxybenzyl 8-methylnonanoate; CAS No. 205687-03-2) is a naturally occurring capsinoid compound found in nonpungent chili peppers. Although the safety of synthetically produced dihydrocapsiate has been previously evaluated, the purpose of this 13-week gavage toxicity study is to evaluate dihydrocapsiate produced with a slightly modified manufacturing process. Sprague-Dawley rats, 10 rats/sex/group, 6 weeks of age at study initiation, were administered the dihydrocapsiate daily by gavage at dose levels of 0 (vehicle), 100,300, or 1000 mg/kg/day. The rats were observed for antimortem and postmortem signs of toxicity, including changes in clinical signs, body weights, food consumption, water intake, ophthalmology, clinical pathology (clinical chemistry, hematology, urinalysis), tissue findings (macroscopic and microscopic examination), as well as organ weights. There were no changes observed in clinical signs, body weight, food consumption, water intake, ophthalmology, urinalysis, hematology, or blood chemistry that were attributable to the administration of dihydrocapsiate. The only change observed attributable to the dihydrocapsiate administration involved the liver and that change occurred only at the high dose (1000 mg/kg). Both sexes had an increase in organ weights, but this increase correlated with a change in histopathology (i.e., hepatocyte hypertrophy) only in the males. No dihydrocapsiate-related histopathological changes were observed in males at doses ≤300 mg/kg or in females at any of the doses tested (≤1000 mg/kg). It was concluded that the no observed adverse effect level (NOAEL) of dihydrocapsiate was 300 mg/kg/day for male rats and 1000 mg/kg/day for female rats in this 13 week gavage study.

Subchronic Toxicity of Thalidomide in Rodents After 13 Weeks of Oral Administration

1999 ◽  
Vol 18 (5) ◽  
pp. 337-352 ◽  
Author(s):  
Steve K. Teo ◽  
Nancy J. Trigg ◽  
Mary E. Shaw ◽  
J. Michael Morgan ◽  
Steve D. Thomas
Keyword(s):  
Food Consumption ◽  
Dose Response ◽  
Clinical Chemistry ◽  
Female Rats ◽  
Male Rats ◽  
Lumbar Spinal Cord ◽  
High Dose ◽  
Significant Finding ◽  
Lower Body ◽  
Body Weights

The subchronic toxicology of thalidomide was determined in CD-1 mice and F344 rats. Animals (10/sex/dose) were orally dosed at 30,300, and 3000 mg/kg/day over 13 weeks. Control animals were given 1% carboxymethylcellulose. No thalidomide-related mortality occurred throughout the study. Some species and sex differences were seen. In mice, thalidomide had no effect on body weight, food consumption, ophthalmic function or clinical chemistry/hematology, but a dose-dependent orange-pink urine was observed in both sexes. The discoloration was probably due to chromogenic breakdown products of thalidomide. The only significant finding in the mouse study was dose-related hepatic centrilobular hypertrophy in the males. This appeared only at the highest dose in the females. The hypertrophy was correlated with increased liver weight for the high dose of both sexes suggesting enzyme induction. In rats, thalidomide produced lower body weights in both sexes compared to control with a dose-response more evident in males. Male rats dosed at 30, 300, and 3000 mg/kg had body weights that were 8, 11, and 19% below control weight just before necropsy. Corresponding female rats were only 6–7% below control weights at all dose levels. Lower food consumption was observed in male rats and varied between 6–13% below control with no dose-response. Decreased forelimb strength was noted in males and could be due to the lower body weights. Functional observational battery tests and histopathology of the sural nerve and lumbar spinal cord sections suggested that the rat did not develop thalidomide-induced peripheral neuropathy. Mild anemia and leukopenia were seen only in some treated males. A decrease in total and free T4 was more consistent in females. Both sexes had lower thymus weights with no histological correlate compared to control. The no-observed-adverse-effect level for mice and female rats were 3000 mg/kg and 30 mg/kg for male rats.

An analysis of the course of infection of Moniliformis dubius (Acanthocephala) in rats

Parasitology ◽  
1972 ◽  
Vol 64 (3) ◽  
pp. 517-523 ◽  
Author(s):  
D. W. T. Crompton ◽  
D. E. Walters
Keyword(s):  
Wistar Rats ◽  
Female Rats ◽  
Male Rats ◽  
Male And Female ◽  
Oral Infections ◽  
The Third ◽  
Male And Female Rats ◽  
Female Wistar Rats ◽  
Average Recovery Rate ◽  
Marked Decline

An analysis of the course of infection of mixed oral infections of 12 cystacanths of Moniliformis dubius in 174 male and 179 female Wistar rats has been undertaken.There was a marked decline in the average recovery rate of worms of both sexes from hosts of both sexes during the course of the infection.Female worms from both male and female rats showed, on average, a greater power of survival than male worms from the third period (10–13 weeks) onwards.Male rats were found to retain, on average, a greater number of worms of both sexes than female rats.We wish to thank Miss Susan Arnold and Mr David Barnard for excellent technical help.

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