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 ◽  
...  

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.

Author(s):  
A. Ashamu Ebenezer ◽  
A. Oyeniran David ◽  
T. Awora Koyinsola ◽  
O. T. Olayemi ◽  
O. Oyewo Olutoyi

Hibiscus sabdariffa is a common garden plant native to warm-temperate, subtropical and tropical regions throughout the world, used in traditional medicine. It is mostly cultivated for its flowers. The calyces are used as a refrigerant in form of tea (especially in making the sorrel drink popularly known as ‘zobo’ in Nigeria), jellies and jam. Aim: This study evaluates the effects of aqueous leaves extract of Hibiscus sabdariffa on the body, testis weight, histology of the testes and sperm parameter of adult male Wistar rats. Methodology: Twenty-five adult male wistar rats of 10-12 weeks and weighing about 120-140g were divided into four groups (A, B, C and D) (five rats / group), Group A was kept as control and B, C, D were administered 250 mg, 500 mg, 1000 mg  of Hibiscus sabdarfia leaf extract per Kg body weight for 8 weeks. The rats in each group were fed with rat feed and water ad libitum. Administration was by means of an oral cannula. At the end of each experimental period, the rats were sacrificed by cervical dislocation, the testes were harvested and immediately fixed in Bouin’s fluid for histological procedure. However, as soon as the animals were sacrificed, the cauda epididymis was removed and semen analysis was carried out immediately. Results: There was a significant decrease in body weight of all the test groups at (P <0.05) and a significant decrease in the testes of the rats in group D when compared with the control group. Statistical analysis revealed decrease in sperm count, motility and viability with a significance decrease (P <0.05) in group D only as compared to control group. The histoarchitecture revealed significant degenerative changes characterized by vacuolization in the intestitium and seminiferous epithelium when compared with the control group. Conclusion: The aqueous leaves extract of Hibiscus sabdariffa appears to have adverse effects on the fertility of male rats especially when taken over a long period of time.


2020 ◽  
Vol 7 ◽  
Author(s):  
Zhen Dong ◽  
Shou-ye Xing ◽  
Ji-yu Zhang ◽  
Xu-zheng Zhou

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.


2017 ◽  
Vol 15 (1) ◽  
pp. 40-43
Author(s):  
Anup Pandeya ◽  
Chandra Bhushan Jha ◽  
Smriti Karki ◽  
Gajendra Prashad Rauniar

Background and Objectives: Nephrotoxicity is one of the limiting factors for using doxorubicin as an anticancer chemotherapeutic. Reactive oxygen species and cytokines have been implicated in the nephrotoxicity induced by doxorubicin. The main objective of the present study is to identify and compare the histomorphological features in kidneys of albino rats and gross morphological features such as weight of rats and weight of the kidneys due to administration of doxorubicin. Materials and Methods: In the study, albino rats were taken as the animal model. Sixty animals were taken as the sample size. They were divided into two equal groups: experimental (n=30) and control (n=30). Rats of experimental group were treated with anticancer drug doxorubicin at a single intraperitoneal dose of 10 mg/kg body weight while the Control group of rats received a similar volume of 0.9% normal saline. The ethical clearance was taken prior to the research from IERB committee BPKIHS Dharan.  Results: Our results showed that there was high effect of drug in experimental groups of rats. It was seen that there was significant decrease in the body weight and weight of kidneys. The final body weight and kidney weight between experimental and control group showed the significant difference. Similarly there were no significant differences in the normal architecture between the male and female rats. The normal renal histological features were seen on the kidneys in the control group whereas the rats intervened with the drug had some disrupted histological features which reveal the toxicity of the drugs in the kidneys. Conclusion: The study showed toxicity of the drug in the kidneys of experimental groups of rats irrespective of gender and suggest that doxorubicin causes significant loss of the body weight and weight of kidneys and causes the disruption in the normal histological features.


2021 ◽  
Vol 10 (5) ◽  
pp. 298-315
Author(s):  
Kunjan Shah ◽  
◽  
Sudhakar Jadhav ◽  
Manish Patel ◽  
Jaydip Mistry ◽  
...  

TGT Primaage is one of the astonishing extracts, obtained from a combination of Moringa oleifera and Centella asiatica. At present, there is no finding reported regardin g the repeated exposure of this extract. This study investigates the No Observed Adverse Effect Level (NOAEL) and effects of repeated-dose administration of Astragalin and Isoquercetin (components of interest) present in TGT Primaage on Wistar rats. Rats were divided into 3 treatment and a control group (10 rats/sex/group). To assess reversibility, persistence, or delayed effect, additional control and high dose groups were treated similarly and observed further without any treatment. TGT Primaage was administered orally, through gavage for 90 days, at 0, 250, 500, and 1000 mg/kg body weight/day. No mortality, morbidity, and clinical sign of toxicity was observed. Abnormality related to neurological and functional parameters was not seen. No change in body weight and food consumption was observed. Treatment did not lead to any adverse effect in clinical pathology parameters and organ weights. TGT Primaage did not alter morphological and histopathological characteristics of organs. From these results, it is evident that TGT Primaage appears to be safe and devoid of any toxicity. The No Observed Adverse Effect Level (NOAEL) of TGT Primaage for both sexes were found to be 1000 mg/kg body weight/day


2016 ◽  
Vol 85 (1) ◽  
pp. 99-104
Author(s):  
Branislav Gálik ◽  
Daniel Bíro ◽  
Milan Šimko ◽  
Miroslav Juráček ◽  
Marcela Capcarová ◽  
...  

The aim of this study was to analyse the effects of different daily intakes of rapeseed bee pollen on the growth and biochemical blood serum indicators in male and female rats. A total of 40 clinically healthy male and female Wistar rats were randomly divided into four groups. In the control group (C) rats were fed a standard complete diet; in the experimental groups standard diets were supplemented with different doses of bee pollen. Treatment group T1 was given standard diet with the addition of bee pollen at a 0.3% concentration; in group T2 the addition was 0.5%; and in group T3 it was 0.75%. The experimental period lasted for 90 days. A significant effect (P < 0.05) of bee pollen on the body weight gain and feed conversion ratio of female rats was found. Significantly (P < 0.05) higher cholesterol concentration in blood serum of male rats was found in the groups with bee pollen addition (groups T2 and T3) compared to the control group. Lower triglyceride serum content in all female experimental groups (T1 and T3) was observed in comparison to the control. Higher serum cholesterol content in the experimental female rats was detected; significant differences were analysed in groups T1 and T3 compared to the control female group. Rapeseed bee pollen at concentrations of 0.5 and 0.75% positively affected the body weight gain of female rats, however, with higher feed consumption (P < 0.05). Rapeseed bee pollen reduced the triglycerides serum content in female rats and increased the cholesterol serum content in male and female rats (P < 0.05).


2021 ◽  
Vol 12 ◽  
Author(s):  
John Turner ◽  
Albert Licollari ◽  
Emil Mihalcea ◽  
Aimin Tan

NAD+ is an abundant molecule in the body and vital to all living cells. NAD+ levels decline with age, and this decline correlates with age-related diseases. Therefore, sustaining NAD+ levels offers potential benefits to healthspan and longevity. Here we conducted toxicity studies to evaluate the safety of Restorin® NMN, a high purity form of the direct NAD+ precursor, β-nicotinamide mononucleotide (NMN). Based on the preliminary toxicity study and a 14-days repeated dose toxicity study at a higher dose level exposure, Restorin® NMN was administered orally to Sprague-Dawley rats for 91 days followed by a 14-days recovery period. The oral doses of 500, 1,000, and 2000 mg/kg/day were compared. There were no test item-related findings that could be considered adverse events in animals dosed at 500 mg/kg/day. The findings in the Restorin® NMN high dose group (2000 mg/kg/day) were similar to the reference item (Nicotinamide Riboside Chloride) dosed at 1740 mg/kg/day: reduced body weight, reductions in body weight gains, and diminished food consumption. In conclusion, the No-Observed-Adverse-Effect-Level (NOAEL) for Restorin® NMN is 1,000 mg/kg/day in female rats and 500 mg/kg/day in male rats, and the Low-Observed-Adverse-Effect-Level (LOAEL) for Resotrin® NMN is 2000 mg/kg/day.


2005 ◽  
Vol 24 (4_suppl) ◽  
pp. 25-39 ◽  
Author(s):  
Yasunori Nakamura ◽  
Izuki Bando ◽  
John H. Mennear ◽  
Bruce K. Bernard

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.


Author(s):  
Vidushi Chaurasia ◽  
Madan Lal Aggarwal ◽  
Manoj Chandra Garg

Aims: The present experiment was conducted (comparative study) to determine the effect of single and repeated exposure of Penoxsulam herbicide by topical route. Study Design: To assess acute toxicity, rats were topically exposed by Penoxsulam at 2000 mg/kg body weight and all the animals were observed for 14 days experiment period while, in Subacute toxicity , the rats were topically exposed with Penoxsulam at three multiple dose levels; 200, 500, 1000 mg/kg body. weight once daily for 28 days. Place and Duration of Study: Toxicology department, Shriram Institute for Industrial Research, Delhi (INDIA), June 2018 and June 2019. Methodology: Acute study was carried out in 10 wistar rats and in subacute study the wistar rats were divided into 4 groups i.e., control group, low dose group, middle group, high dose group; 5 male and 5 female rats/ group at the age of 2-3 kg were exposed over a period of 28 days. After dose application the patch was removed and the test site were cleaned with cotton moistened with distilled water. Results: In both toxicity study found that there were no clinical signs of skin reactions (Draize method) and no significant P>0.05 changes were observed in Bodyweight, Biochemistry, and Histopathology among the treated as well as in control group of animals. Therefore, data of this study supports that topical exposure of Penoxsulam in rats were shown normal histology of liver, kidney, and skin at the multiple doses besides this; Penoxsulam does not have potential to produce acute and subacute adverse systemic toxic reaction to the animals. Conclusion: Therefore, data of this study supports that topical exposure of Penoxsulam in rats were shown normal histology of liver, kidney, and skin at the multiple doses besides this; Penoxsulam does not have potential to produce acute and subacute adverse systemic toxic reaction to the animals.


2020 ◽  
Vol 44 (1) ◽  
pp. 76-88
Author(s):  
A. Ajibola ◽  
K. H. Erlwanger

In the study, the growth pattern, morphometric and morphological changes in the gastrointestinal tract of growing male and female Sprague-Dawley rats fed crude honey (CH)-supplemented diets as measures of nutrient utilization, digestive functions and healthy growth were investigated. Thirty-five suckling (7-day old male and female) rats were fed CH either as low (10mLkg-1 BW) or high (20mLkg-1 BW) dose daily via stomach tube for 14 days, while the control group was gavaged with distilled water. Rats were kept with their dams to nurse freely between gavages. On weaning, CH was mixed with commercial rat feed as low (20%) or high, 50% (volume/weight, v/w), while 20% (v/w) tap water was added to the control diet. The feed intake of honey-fed male rats and control (infant: 6 – 10g; adult:31 – 38g) was significantly higher (p < 0.05) than their high dose-diet mates (infant: 5 – 8g; adult: 31 – 38g). All the rats were killed at 13 weeks old for gross and microscopic measurements of the abdominal viscera. Grossly, there were no significant differences (p ≥ 0.05) in the relative lengths (%BW) and weight: length ratio (g cm-1 ) of the small and large intestines in both sexes. Crude honey increased the absolute and relative weights of the caecum (1.73 ± 0.05g; 0.38 ± 0.02%BW) and pancreas (2.52 ± 0.11g; 0.55 ± 0.03%BW), with significant influence (p<0.05) in the male rats. In addition, dietary inclusion of CH at low dose enhanced intestinal villi growth in height (84.0 ± 4.0µm) and width (25.2 ± 1.5µm). Dietary supplementation with crude honey also enhanced body weight gain of male rats (495.52 ± 8.98g) and females (242.52 ± 6.87g), improved abdominal organs' functional size: liver (10.92 ± 0.32g; 2.72 ± 0.13%BW); spleen (1.25 ± 0.06g; 0.27 ± 0.02%BW), devoid of pathological changes, as shown by liver histomorphology (1.2 ± 0.3) and normal hepatocellular architecture thereby conferring nutritional and health benefits on animals nurtured in confinement.


Author(s):  
A. Bob-Chile Agada ◽  
N. Nwachukwu ◽  
C. O. Ibegbulem ◽  
A. C. Ene

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.


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