Toxicological effects of carbosulfan in rats

2015 ◽  
Vol 32 (7) ◽  
pp. 1335-1343 ◽  
Author(s):  
Christopher Didigwu Nwani ◽  
Narottam Das Agrawal ◽  
Suchita Raghuvanshi ◽  
Amita Jaswal ◽  
Sadhana Shrivastava ◽  
...  

Carbosulfan is often used in agriculture for pest control on crops and for treatment against pyrethroid-resistant mosquitoes. This study investigated the impact of carbosulfan on oxidative stress markers, antioxidant defense, hematological, biochemical, and enzymological parameters in Sprague Dawley rats. Rats were orally administered carbosulfan doses of 1.02 to 10.20 mg/kg body weight daily; after 96 h, blood samples were taken, and the liver, kidney, and brain were dissected out for study. Results indicate that carbosulfan significantly increased the levels of lipid peroxidation and suppressed the activity of reduced glutathione, glutathione reductase, catalase, glucose-6-phosphate dehydrogenase, and adenosine triphosphatase. A mixed trend was observed in the activity of superoxide dismutase, while an increase was observed in the levels of serum uric acid, urea, aspartate aminotransferase, and alanine aminotransferase. Hemoglobin and albumin levels decreased but no significant differences were observed in creatinine and bilirubin levels. Future studies should include a more detailed analysis of the effects of chronic carbosulfan exposure on these biomarkers to further assess the impact of the pesticide on mammalian models.

2021 ◽  
pp. 1-8
Author(s):  
S. Melker Hagsäter ◽  
Robert Pettersson ◽  
Axel Holmäng ◽  
Elias Eriksson

Abstract Objective: Whereas numerous experimental and clinical studies suggest a complex involvement of serotonin in the regulation of anxiety, it remains to be clarified if the dominating impact of this transmitter is best described as anxiety-reducing or anxiety-promoting. The aim of this study was to assess the impact of serotonin depletion on acquisition, consolidation, and expression of conditioned fear. Methods: Male Sprague–Dawley rats were exposed to foot shocks as unconditioned stimulus and assessed with respect to freezing behaviour when re-subjected to context. Serotonin depletion was achieved by administration of a serotonin synthesis inhibitor, para-chlorophenylalanine (PCPA) (300 mg/kg daily × 3), (i) throughout the period from (and including) acquisition to (and including) expression, (ii) during acquisition but not expression, (iii) after acquisition only, and (iv) during expression only. Results: The time spent freezing was significantly reduced in animals that were serotonin-depleted during the entire period from (and including) acquisition to (and including) expression, as well as in those being serotonin-depleted during either acquisition only or expression only. In contrast, PCPA administrated immediately after acquisition, that is during memory consolidation, did not impact the expression of conditioned fear. Conclusion: Intact serotonergic neurotransmission is important for both acquisition and expression of context-conditioned fear.


2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Catherine Crinigan ◽  
Matthew Calhoun ◽  
Karen L. Sweazea

Chronic high fat feeding is correlated with diabetes and kidney disease. However, the impact of short-term high fat diets (HFD) is not well-understood. Six weeks of HFD result in indices of metabolic syndrome (increased adiposity, hyperglycemia, hyperinsulinemia, hyperlipidemia, hyperleptinemia, and impaired endothelium-dependent vasodilation) compared to rats fed on standard chow. The hypothesis was that short-term HFD would induce early signs of renal disease. Young male Sprague-Dawley rats were fed either HFD (60% fat) or standard chow (5% fat) for six weeks. Morphology was determined by measuring changes in renal mass and microstructure. Kidney function was measured by analyzing urinary protein, creatinine, and hydrogen peroxide (H2O2) concentrations, as well as plasma cystatin C concentrations. Renal damage was measured through assessment of urinary oxDNA/RNA concentrations as well as renal lipid peroxidation, tumor necrosis factor alpha (TNFα), and interleukin 6 (IL-6). Despite HFD significantly increasing adiposity and renal mass, there was no evidence of early stage kidney disease as measured by changes in urinary and plasma biomarkers as well as histology. These findings suggest that moderate hyperglycemia and inflammation produced by short-term HFD are not sufficient to damage kidneys or that the ketogenic HFD may have protective effects within the kidneys.


Nutrients ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1882 ◽  
Author(s):  
Roy Skinner ◽  
Derek Warren ◽  
Soofia Lateef ◽  
Vagner Benedito ◽  
Janet Tou

Apple pomace, which is a waste byproduct of processing, is rich in several nutrients, particularly dietary fiber, indicating potential benefits for diseases that are attributed to poor diets, such as non-alcoholic fatty liver disease (NAFLD). NAFLD affects over 25% of United States population and is increasing in children. Increasing fruit consumption can influence NAFLD. The study objective was to replace calories in standard or Western diets with apple pomace to determine the effects on genes regulating hepatic lipid metabolism and on risk of NAFLD. Female Sprague-Dawley rats were randomly assigned (n = 8 rats/group) to isocaloric diets of AIN-93G and AIN-93G/10% w/w apple pomace (AIN/AP) or isocaloric diets of Western (45% fat, 33% sucrose) and Western/10% w/w apple pomace (Western/AP) diets for eight weeks. There were no significant effects on hepatic lipid metabolism in rats fed AIN/AP. Western/AP diet containing fiber-rich apple pomace attenuated fat vacuole infiltration, elevated monounsaturated fatty acid content, and triglyceride storage in the liver due to higher circulating bile and upregulated hepatic DGAT2 gene expression induced by feeding a Western diet. The study results showed the replacement of calories in Western diet with apple pomace attenuated NAFLD risk. Therefore, apple pomace has the potential to be developed into a sustainable functional food for human consumption.


PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9138
Author(s):  
Abubakar El-Ishaq ◽  
Mohammed A. Alshawsh ◽  
Kein Seong Mun ◽  
Zamri Chik

Asparagus africanus Lam. is a plant used traditionally to treat different ailments. Currently, scanty information is available on its safety. The aim of this study is to determine the acute toxicity of the methanolic extract on vital organs and its associated biochemical parameters. Fifteen female Sprague-Dawley rats were divided into five groups. Group I served as normal control, groups II, III, IV, and V were orally administered single dose of crude extract dissolved in distilled water at 5 mg/kg BW, 50 mg/kg BW, 300 mg/kg BW and 2,000 mg/kg BW. Rats were observed for 14 days and body weights were recorded. On day 15, the rats were sacrificed and blood samples were collected for biochemical and haematological analyses, while the liver and kidneys were sampled for histopathological examination. Body weight and haematology parameters results showed significance difference (p < 0.05) among means of HGB, RDW, RBC, and MCHC; likewise, (p < 0.001) for WBC and platelet among treated groups. Histopathology result showed that kidneys appeared normal while livers were congested with mildly swollen hepatocytes and occasional binucleation. Focal lobular hepatitis was observed in all treated animals. However, hepatic enzymes were not significantly affected and no histopathological harmful effects were observed in kidney. In conclusion, methanolic extracts of A. africanus are safe up to 2,000 mg/kg BW. The obtained results could be used as a justification for the traditional application of the plant for treatment of various ailments.


2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Shahram Paydar ◽  
Ali Noorafshan ◽  
Behnam Dalfardi ◽  
Shahram Jahanabadi ◽  
Seyed Mohammad Javad Mortazavi ◽  
...  

Background. This study examines the impact of one-time direct application of haemostatic agent zeolite–bentonite powder to wounded skin on the healing process in rats. Materials and Methods. 24 male Sprague-Dawley rats were randomly allocated into two groups (n=12): (1) the rats whose wounds were washed only with sterile normal saline (NS-treated) and (2) those treated with zeolite–bentonite compound (ZEO-treated). The wound was circular, full-thickness, and 2 cm in diameter. At the end of the 12th day, six animals from each group were randomly selected and terminated. The remaining rats were terminated after 21 days. Just after scarification, skin samples were excised and sent for stereological evaluation. Results. The results showed a significant difference between the two groups regarding the length density of the blood vessels and diameter of the large and small vessels on the 12th day after the wound was inflicted. Besides, volume density of both the dermis and collagen bundles was reduced by 25% in the ZEO-treated rats in comparison to the NS-treated animals after 21 days. Conclusions. One-time topical usage of zeolite–bentonite haemostatic powder on an animal skin wound might negatively affect the healing process through vasoconstriction and inhibition of neoangiogenesis.


2020 ◽  
Vol 98 (10) ◽  
pp. 667-677
Author(s):  
Olufunto O. Badmus ◽  
Lawrence A. Olatunji

Glucocorticoid therapy has been associated with adverse cardiometabolic effects during pregnancy. Inflammation-mediated cardiac dysfunction, an independent risk factor for morbidity and mortality, has been linked to defective glucose-6-phosphate dehydrogenase (G6PD) dependent antioxidant defenses and increased endoglin expression. We therefore sought to investigate the effects of dexamethasone (DEX) on cardiac endoglin and G6PD-dependent antioxidant defense. Twenty-four rats were randomly assigned to nonpregnant (PRE(–)), DEX-exposed nonpregnant (PRE(–) + DEX), pregnant (PRE(+)), and DEX-exposed pregnant (PRE(+) + DEX) rats, respectively (n = 6 per group). PRE(–) and PRE(+) rats received vehicle (per oral (po)), while PRE(–) + DEX and PRE(+) + DEX groups were administered DEX (0.2 mg/kg po) between gestational days 14 and 19, respectively. Results showed that DEX caused increased cardiac pro-inflammatory markers (adenosine deaminase (ADA) activity, endoglin, vascular cell adhesion molecule-1 (VCAM-1), tissue injury markers (LDH, GGT, AST, ALT, and ALP), metabolic disturbances (elevated fasting plasma glucose, free fatty acid (FFA), lactate, cardiac FFA, and lactate) and depressed G6PD-dependent antioxidant defenses (G6PD activity, reduced glutathione/oxidized glutathione ratio, and nitric oxide) in pregnant and nonpregnant rats. The present study demonstrates that DEX led to increased cardiac endoglin and VCAM-1 that is accompanied by defective G6PD-dependent antioxidant defenses but not cardiac lipid accumulation in both pregnant and nonpregnant rats.


2016 ◽  
Vol 310 (2) ◽  
pp. R115-R124 ◽  
Author(s):  
Kathryn R. Walsh ◽  
Jill T. Kuwabara ◽  
Joon W. Shim ◽  
Richard D. Wainford

Recent studies have implicated a role of norepinephrine (NE) in the activation of the sodium chloride cotransporter (NCC) to drive the development of salt-sensitive hypertension. However, the interaction between NE and increased salt intake on blood pressure remains to be fully elucidated. This study examined the impact of a continuous NE infusion on sodium homeostasis and blood pressure in conscious Sprague-Dawley rats challenged with a normal (NS; 0.6% NaCl) or high-salt (HS; 8% NaCl) diet for 14 days. Naïve and saline-infused Sprague-Dawley rats remained normotensive when placed on HS and exhibited dietary sodium-evoked suppression of peak natriuresis to hydrochlorothiazide. NE infusion resulted in the development of hypertension, which was exacerbated by HS, demonstrating the development of the salt sensitivity of blood pressure [MAP (mmHg) NE+NS: 151 ± 3 vs. NE+HS: 172 ± 4; P < 0.05]. In these salt-sensitive animals, increased NE prevented dietary sodium-evoked suppression of peak natriuresis to hydrochlorothiazide, suggesting impaired NCC activity contributes to the development of salt sensitivity [peak natriuresis to hydrochlorothiazide (μeq/min) Naïve+NS: 9.4 ± 0.2 vs. Naïve+HS: 7 ± 0.1; P < 0.05; NE+NS: 11.1 ± 1.1; NE+HS: 10.8 ± 0.4). NE infusion did not alter NCC expression in animals maintained on NS; however, dietary sodium-evoked suppression of NCC expression was prevented in animals challenged with NE. Chronic NCC antagonism abolished the salt-sensitive component of NE-mediated hypertension, while chronic ANG II type 1 receptor antagonism significantly attenuated NE-evoked hypertension without restoring NCC function. These data demonstrate that increased levels of NE prevent dietary sodium-evoked suppression of the NCC, via an ANG II-independent mechanism, to stimulate the development of salt-sensitive hypertension.


1983 ◽  
Vol 69 (2) ◽  
pp. 105-111 ◽  
Author(s):  
Franco Zunino ◽  
Odoardo Tofanetti ◽  
Adriana Besati ◽  
Ennio Cavalletti ◽  
Giuseppina Savi

Pretreatment of Swiss mice and Sprague-Dawley rats with glutathione (GSH) reduced the acute lethal toxicity of cis-dichlorodiammine platinum (II) (cis-DDP) in a dose-dependent manner. The protection was accompanied by reduction of both body weight loss and by reduction of nephrotoxicity, as measured by a rise in serum blood urea nitrogen (BUN), creatinine levels and by histopathologic changes, which occurred 4 days following cis-DDP treatment. The antitumor effects of cis-DDP on experimental tumor models (P388 and Gross leukemia) were not significantly altered by GSH treatment. It is suggested that the partial protection by GSH from acute toxicity of the antitumor drug is directly related to protection of renal function.


1985 ◽  
Vol 249 (2) ◽  
pp. F213-F219
Author(s):  
S. G. Rostand ◽  
J. Work

To study the association between renal renin release and the pentose pathway, we perfused nonfiltering kidneys from Sprague-Dawley rats with Krebs-Ringer bicarbonate buffer containing 5 mM glucose and 14 g/100 ml bovine serum albumin in the presence or in the absence of 0.25 mM 6-aminonicotinamide (6AN), an inhibitor of glucose-6-phosphate dehydrogenase, the rate-limiting step of the pentose pathway. Eleven kidneys perfused in the absence of 6AN had a renin secretion rate of 7.4 +/- 2.2 ng ANG I X min-1 X ml-1. In six kidneys perfused in the presence of 6AN, renin release was depressed to 0.56 +/- 0.24 ng ANG I X min-1 X ml-1. The renal renin content for four control kidneys was 56 +/- 3.3 ng ANG I X mg-1 X h-1 while in four kidneys perfused with 6AN renal renin content was lower, 35 +/- 2.9 ng ANG I X mg-1 X h-1. In the presence of 5 mM lactate, the renin release of eight nonfiltering kidneys was 0.31 +/- 0.06 ng ANG I X min-1 X ml-1. The addition of 6AN did not further depress renin secretion in the presence of lactate. 6-Aminonicotinamide also completely blocked furosemide-stimulated renin release without having any effect on glomerular filtration rate or furosemide-induced natriuresis. However, 6AN did not inhibit stimulation of renin secretion by isoproterenol. We conclude that 6-aminonicotinamide interferes with renin release by nonfiltering kidneys and also inhibits furosemide-stimulated renin release but does not affect beta-adrenergic-stimulated renin secretion. Glucose but not lactate is important for maintaining augmented rates of renin secretion in nonfiltering kidneys. 6-Aminonicotinamide significantly reduced renal renin content in the presence of glucose.(ABSTRACT TRUNCATED AT 250 WORDS)


2019 ◽  
Vol 172 (1) ◽  
pp. 132-145 ◽  
Author(s):  
Silvia Cirillo ◽  
Fabio Vivarelli ◽  
Eleonora Turrini ◽  
Carmela Fimognari ◽  
Sabrina Burattini ◽  
...  

Abstract Despite the knowledge gap regarding the risk-benefit ratio of the electronic cigarette (e-cig), its use has grown exponentially, even in teenagers. E-cig vapor contains carcinogenic compounds (eg, formaldehyde, acetaldehyde, and acrolein) and free radicals, especially reactive oxygen species (ROS) that cause toxicological effects, including DNA damage. The role of e-cig voltage customization on molecule generation has been reported, but the effects of the resistance on e-cig emissions and toxicity are unknown. Here, we show that the manipulation of e-cig resistance influences the carbonyls production from nonnicotine vapor and the oxidative and inflammatory status in a rat model. Fixing the voltage at the conventional 3.5 V, we observed that the amount of the selected aldehydes increased as the resistance decreased from 1.5 to 0.25 Ω. Under these conditions, we exposed Sprague Dawley rats to e-cig aerosol for 28 days, and we studied the pulmonary inflammation, oxidative stress, tissue damage, and blood homeostasis. We found a perturbation of the antioxidant and phase II enzymes, probably related to the increased ROS levels due to the enhanced xanthine oxidase and P450-linked monooxygenases. Furthermore, frames from scanning electron microscope showed a disorganization of alveolar and bronchial epithelium in 0.25 Ω group. Overall, various toxicological outcomes, widely recognized as smoke-related injuries, can potentially occur in e-cig consumers who use low-voltage and resistance device. Our study suggests that certain “tips for vaping safety” cannot be established, and encourages further independent investigations to help public health agencies in regulating the e-cig use.


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