scholarly journals Chronic Ingestion of High Dosed Phikud Navakot Extraction Induces Mesangiolysis in Rats with Alteration of AQP1 and Hsp60 Expressions

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Kanchana Kengkoom ◽  
Sumate Ampawong
Keyword(s):  
Vascular Function ◽  
Cell Damage ◽  
Protective Role ◽  
Histopathological Study ◽  
High Dose ◽  
Sprague Dawley ◽  
Endothelial Lining ◽  
Sprague Dawley Rats ◽  
Aqp1 Expression ◽  
Chronic Ingestion

Phikud Navakot (PN) is commonly used in Thai traditional medicine for alleviation of cardiovascular and cerebrovascular symptoms; however little is known about the chronic toxicity effects of the extracts from the herbs in PN. Repeated extraction doses of 10, 100, and 1,000 mg/kg/day were randomly administered to both male and female Sprague Dawley rats for 12 months. Histopathological study revealed that mesangiolysis was predominately found at the highest dose. Aquaporin 1 (AQP1) expression in the mesangiolytic glomeruli was significantly lower than in the intact glomeruli. This may be relevant to an imbalance of vascular function manifested by AQP1 alteration. In the mesangiolytic glomeruli, 60 kDa heat shock protein (Hsp60) was significantly upregulated on the endothelial lining cells of aneurysm and vascular cyst. Hsp60 increase may be related to endothelial cell damage due to its intracellular protective role. Blood urea nitrogen and creatinine levels remained within their normal range indicating well-functioning renal reserve function. In conclusion, high dosed PN may affect the endothelium leading to inability of vascular permeability and consequence to mesangiolysis. Our results suggest that only a high dose of chronic oral administration of PN is relatively toxic in association with mesangiolysis. The NOAEL was determined to be 100 mg/kg/day.

scholarly journals Antidepressant-Like Effect of Lipid Extract ofChanna striatusin Postpartum Model of Depression in Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Mohamed Saleem Abdul Shukkoor ◽  
Mohamad Taufik Hidayat Bin Baharuldin ◽  
Abdul Manan Mat Jais ◽  
Mohamad Aris Mohamad Moklas ◽  
Sharida Fakurazi ◽  
...  
Keyword(s):  
Postpartum Period ◽  
Estradiol Benzoate ◽  
Plasma Corticosterone ◽  
Positive Control ◽  
Lipid Extract ◽  
High Dose ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Malay Population ◽  
Swimming Test

Postpartum depression affects 15% of women.Channa striatus, a freshwater fish, is consumed in local Malay population as a rejuvenating diet during postpartum period. This study evaluated the antidepressant-like effect of lipid extract ofC. striatusfillet and its mechanism of action in female Sprague-Dawley rats in postpartum model of depression. The rats were ovariectomized and treated with high dose of progesterone and estradiol benzoate for 23 days to have hormone-simulated pregnancy. The day 24 and afterwards were considered as the postpartum period. During the postpartum period, lipid extract was administered at 125, 250, and 500 mg/kg through intraperitoneal route for 15 days. Fluoxetine (10 mg/kg) was used as the positive control. On postpartum day 15, the animals were tested in forced swimming test (FST) and open field test (OFT) followed by biochemical analysis. Withdrawal of hormone administration during the postpartum period induced depressive-like behavior in FST. Administration of lipid extract reversed that depressive-like behavior at 125, 250, and 500 mg/kg in FST. In OFT, it decreased the exploratory activity. The mechanism of the antidepressant-like effect may be mediated through the decrease in plasma corticosterone, increase in plasma oxytocin, and decrease in nuclear factor-kappa B in prefrontal cortex of rats.

The Hepatoprotective Role of Warburgia salutaris and Iso-Mukaadial Acetate on Carbon tetrachloride Intoxicated Rats Model

2021 ◽  
Vol 17 ◽  
Author(s):  
Gideon Ayeni ◽  
Mthokozisi Blessing Cedric Simelane ◽  
Shahidul Islam ◽  
Ofentse Jacob Pooe
Keyword(s):  
Carbon Tetrachloride ◽  
Hepatic Injury ◽  
Antioxidant Properties ◽  
Hepatic Necrosis ◽  
Protective Role ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Isolated Compound

Background: Medicinal plants together with their isolated bioactive compounds are known for their antioxidant properties which constitute therapeutic agents that are routinely employed in the treatment of liver diseases. Aims of the Study: The current study sought to explore the protective role of Warburgia salutaris and its isolated compound, iso-mukaadial acetate against carbon tetrachloride (CCl4)-induced hepatic injury. Methods: Thirty-five male Sprague Dawley rats were divided into seven groups of five animals each and injected with CCl4 to induce hepatic injury. Results: Treatment with the crude extract of W. salutaris and of iso-mukaadial acetate significantly reduced the levels of alkaline phosphatase, alanine and aspartate aminotransaminases, total bilirubin and malondialdehyde in a dose dependent manner, when compared to untreated groups. Liver histology revealed a reduction in hepatic necrosis and inflammation. Conclusion: The current investigation has demonstrated that W. salutaris extract and iso-mukaadial acetate could mitigate the acute liver injury inflicted by a hepatotoxic inducer in rats.

Ultrastructural changes of Basolateral Amygdaloid nuclei in the Sprague Dawley rats brain following exposure to naphthalene balls

2021 ◽  
Vol 12 (2) ◽  
pp. 1272-1275
Author(s):  
Angu Bala Ganesh K S V ◽  
Sujeet Shekhar Sinha ◽  
Kesavi Durairaj ◽  
Abdul Sahabudeen K
Keyword(s):  
Structural Changes ◽  
Corn Oil ◽  
Chromatin Condensation ◽  
Ultrastructural Changes ◽  
High Dose ◽  
Model Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
The Brain ◽  
Amygdaloid Nuclei

Naphthalene is a bicyclic aromatic constituent commonly used in different domestic and marketable applications comprising soil fumigants, lavatory scent disks and mothballs. Accidentally, workers, children and animals are exposed to naphthalene mothballs, so there is a need to study the pathology behind this chemical toxicity. The current study was carried out to assess the ultra structural changes of basolateral amygdaloid nuclei in the Sprague Dawley rats brain in association to naphthalene toxicity. The toxicity model group was administered with naphthalene (200 and 400mg) using corn oil as a vehicle for 28 days. The post delayed toxicity of naphthalene high dose ingestion was also assessed in rats. After the experimental period, the brain tissue was processed to observe the ultra structural changes using a transmission electron microscope. The alterations in cell organelles, nuclei damage, mitochondrial swelling, chromatin condensation suggested naphthalene induced damage in the neurons of the basolateral amygdala of the brain in the toxicity model group. These experimental trials provide information about the alert of mothball usage in the home and identify risks linked with accidental exposure and misuse.

scholarly journals Erythropoietin Produces a Dual Effect on Carotid Body Chemoreception in Male Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Christian Arias-Reyes ◽  
Sofien Laouafa ◽  
Natalia Zubieta-DeUrioste ◽  
Vincent Joseph ◽  
Aida Bairam ◽  
...  
Keyword(s):  
Carotid Body ◽  
No Synthase ◽  
Male Rats ◽  
High Dose ◽  
No Production ◽  
Sprague Dawley ◽  
En Bloc ◽  
No Synthase Inhibitor ◽  
Sprague Dawley Rats ◽  
Synthase Inhibitor

Erythropoietin (EPO) regulates respiration under conditions of normoxia and hypoxia through interaction with the respiratory centers of the brainstem. Here we investigate the dose-dependent impact of EPO in the CB response to hypoxia and hypercapnia. We show, in isolated “en bloc” carotid body (CB) preparations containing the carotid sinus nerve (CSN) from adult male Sprague Dawley rats, that EPO acts as a stimulator of CSN activity in response to hypoxia at concentrations below 0.5 IU/ml. Under hypercapnic conditions, EPO did not influence the CSN response. EPO concentrations above 0.5 IU/ml decreased the response of the CSN to both hypoxia and hypercapnia, reaching complete inhibition at 2 IU/ml. The inhibitory action of high-dose EPO on the CSN activity might result from an increase in nitric oxide (NO) production. Accordingly, CB preparations were incubated with 2 IU/ml EPO and the unspecific NO synthase inhibitor (L-NAME), or the neuronal-specific NO synthase inhibitor (7NI). Both NO inhibitors fully restored the CSN activity in response to hypoxia and hypercapnia in presence of EPO. Our results show that EPO activates the CB response to hypoxia when its concentration does not exceed the threshold at which NO inhibitors masks EPO’s action.

Impaired NO-mediated vasodilation with increased superoxide but robust EDHF function in right ventricular arterial microvessels of pulmonary hypertensive rats

2007 ◽  
Vol 292 (6) ◽  
pp. H2737-H2744 ◽  
Author(s):  
Masahito Kajiya ◽  
Masanori Hirota ◽  
Yousuke Inai ◽  
Takahiko Kiyooka ◽  
Taro Morimoto ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Pressure Overload ◽  
Suppressive Effect ◽  
Protective Role ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Small Arteries ◽  
Sprague Dawley Rats ◽  
Endothelial Nitric Oxide ◽  
Arteriolar Vasodilation

Pulmonary hypertension (PH) causes right ventricular (RV) hypertrophy and, according to the extent of pressure overload, eventual heart failure. We tested the hypothesis that the mechanical stress in PH-RV impairs the vasoreactivity of the RV coronary microvessels of different sizes with increased superoxide levels. Five-week-old male Sprague-Dawley rats were injected with monocrotaline ( n = 126) to induce PH or with saline as controls ( n = 114). After 3 wk, coronary arterioles (diameter = 30–100 μm) and small arteries (diameter = 100–200 μm) in the RV were visualized using intravital videomicroscopy. We evaluated ACh-induced vasodilation alone, in the presence of Nω-nitro-l-arginine methyl ester (l-NAME), in the presence of tetraethylammonium (TEA) or catalase with or without l-NAME, and in the presence of SOD. The degree of suppression in vasodilation by l-NAME and TEA was used as indexes of the contributions of endothelial nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF), respectively. In PH rats, ACh-induced vasodilation was significantly attenuated in both arterioles and small aretries, especially in arterioles. This decreased vasodilation was largely attributable to reduced NO-mediated vasoreactivity, whereas the EDHF-mediated vasodilation was relatively robust. The suppressive effect on arteriolar vasodilation by catalase was similar to TEA in both groups. Superoxide, as measured by lucigenin chemiluminescence, was significantly elevated in the RV tissues in PH. SOD significantly ameliorated the impairment of ACh-induced vasodilation in PH. Robust EDHF function will play a protective role in preserving coronary microvascular homeostasis in the event of NO dysfunction with increased superoxide levels.

scholarly journals Toxicity associated with ingestion of a polyacrylic acid hydrogel dog pad

2018 ◽  
Vol 30 (5) ◽  
pp. 708-714 ◽  
Author(s):  
David C. Dorman ◽  
Melanie L. Foster ◽  
Brooke Olesnevich ◽  
Brad Bolon ◽  
Aude Castel ◽  
...  
Keyword(s):  
Motor Activity ◽  
Polyacrylic Acid ◽  
Muscle Tone ◽  
Clinical Signs ◽  
High Dose ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Before And After ◽  
Acute Neurotoxicity ◽  
Disposable Diapers

Superabsorbent sodium polyacrylate polymeric hydrogels that retain large amounts of liquids are used in disposable diapers, sanitary napkins, and other applications. These polymers are generally considered “nontoxic” with acute oral median lethal doses (LD50) >5 g/kg. Despite this favorable toxicity profile, we identified a novel toxic syndrome in dogs and rats following the ingestion of a commercial dog pad composed primarily of a polyacrylic acid hydrogel. Inappropriate mentation, cerebellar ataxia, vomiting, and intention tremors were observed within 24 h after the ingestion of up to 15.7 g/kg of the hydrogel by an adult, castrated male Australian Shepherd mix. These observations prompted an experimental study in rats to further characterize the toxicity of the hydrogel. Adult, female Sprague Dawley rats ( n = 9) were assessed before and after hydrogel ingestion (2.6–19.2 g/kg over 4 h) using a functional observation battery and spontaneous motor activity. Clinical signs consistent with neurotoxicity emerged in rats as early as 2 h after the end of hydrogel exposure, including decreased activity in an open field, hunched posture, gait changes, reduced reaction to handling, decreased muscle tone, and abnormal surface righting. Hydrogel-exposed rats also had reduced motor activity when compared with pre-exposure baseline data. Rats that ingested the hydrogel did not develop nervous system lesions. These findings support the conclusion that some pet pad hydrogel products can induce acute neurotoxicity in animals under high-dose exposure conditions.

Abstract P214: The Non-canonical Stress Tolerance Cascade for Toll-like Receptor 9 in the Vasculature Signals Through Liver Kinase B1

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Cameron G McCarthy ◽  
Camilla F Wenceslau ◽  
Safia Ogbi ◽  
Theodora Szasz ◽  
R.Clinton Webb
Keyword(s):  
Protein Kinase ◽  
Stress Tolerance ◽  
Vascular Function ◽  
Cytosolic Calcium ◽  
Toll Like Receptor ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Liver Kinase B1 ◽  
Tlr9 Activation

Toll-like receptor (TLR)9 is a pattern recognition receptor of the innate immune system. Recently, a non-canonical stress tolerance pathway has been reported for TLR9 in non-immune cells (cardiomyocytes and neurons), independent of inflammatory signaling. It was observed that TLR9 inhibited sarco/endoplasmic reticulum Ca 2+ -ATPase (SERCA)2, increasing cytosolic calcium, and resulting in 5’ AMP-activated protein kinase (AMPK)α activation. In our laboratory, we have reported that TLR9 treatment in vivo causes arterial dysfunction that contributes to the pathogenesis of hypertension and that these phenotypes occurred in conjunction with vascular AMPKα phosphorylation (Thr172). However, whether a dysregulation in calcium homeostasis via the non-canonical stress tolerance cascade underlies the impaired vascular function after TLR9 stimulation needs to be clarified. We hypothesized that TLR9 activation would inhibit SERCA2 activity in the vasculature. SERCA2 activity was assessed using a luciferase-based ATP quantification kit. Microsomes were isolated from pooled aortae of Sprague-Dawley rats and subjected to treatment with either Vehicle (Veh) or ODN2395 (2 μM), with or without a SERCA2 inhibitor (thapsigargin; 1 μM). The presence of thapsigargin increased ATP concentrations similarly in both Veh and ODN2395 [ATP (μM), Veh: 19±3 vs. Veh+thapsigargin: 140±35; ODN2395: 22±9 vs. ODN2395+thapsigargin: 129±12, both p<0.05], suggesting TLR9 activation did not inhibit SERCA2 activity. Next, MRA from Sprague-Dawley rats were divided into three sections for Western blot analysis of AMPKα-activating kinases, specifically calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) and liver kinase B1 (LKB1). ODN2395 alone did not increase protein expression of phospho-CaMKK2 Ser511 (p>0.05), again suggesting calcium-independent activation of AMPKα. However, ODN2395 did increase phospho-LKB1 Ser428 (3.8 fold vs. Veh, p<0.05), and this increase in expression was inhibited by pre-incubation with TLR9 antagonist ODN2088 (20 μM) (p>0.05). These results suggest that the TLR9 non-canonical stress tolerance pathway in the vasculature is mediated by LKB1, and not SERCA2 inhibition.

Impaired follicular development and endocrine disorders in female rats by prepubertal exposure to toxic doses of cadmium

2020 ◽  
Vol 36 (2) ◽  
pp. 63-75
Author(s):  
Saman Saedi ◽  
Mohammad Reza Jafarzadeh Shirazi ◽  
Mohammad Javad Zamiri ◽  
Mehdi Totonchi ◽  
Mohammad Dadpasand ◽  
...  
Keyword(s):  
Steroid Hormones ◽  
Endocrine System ◽  
Follicular Development ◽  
Female Rats ◽  
High Dose ◽  
Endocrine Disorders ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Puberty Onset ◽  
Different Doses

Cadmium (Cd) has been associated with several physiological problems including reproductive and endocrine system dysfunction resulting in temporary infertility. The principal objective of this project was to investigate the effects of prepubertal exposure to toxic doses of Cd on puberty onset, the endocrine system, and follicular development. For this purpose, 16 female Sprague-Dawley rats weaned on postnatal day (PND) 21 were randomly divided into 4 groups ( n = 4 per group). The treatments were as follows: 0, 25, 50, and 75 mg/kg/day of cadmium chloride (CdCl2) by oral gavage from PND 21 to observation of first vaginal opening (VO). The results demonstrated that prepubertal exposure to different doses of CdCl2 delays the age of VO, first diestrus, and first proestrus via altering the concentrations of estradiol and progesterone. The low level of these steroid hormones contributed to lower differentiation and maturation of follicles and it finally led to reduced ovarian reservoir of follicles and impaired follicular development. The number of atretic follicles and secondary follicles with premature cavity increased in rats that received a high dose of CdCl2, whereas the number of secondary follicles and corpora luteum decreased in the same circumstances. Taken together, these data suggest that prepubertal exposure to toxic doses of Cd delays the onset of puberty via disorderliness in the concentration of steroid hormones and reduces the ovarian reservoir of follicles, as well as folliculogenesis.

scholarly journals Gynura procumbens Standardised Extract Reduces Cholesterol Levels and Modulates Oxidative Status in Postmenopausal Rats Fed with Cholesterol Diet Enriched with Repeatedly Heated Palm Oil

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Khuzaidatul Azidah Ahmad Nazri ◽  
Norsyahida Mohd Fauzi ◽  
Fhataheya Buang ◽  
Qodriyah Haji Mohd Saad ◽  
Khairana Husain ◽  
...  
Keyword(s):  
Palm Oil ◽  
Cell Damage ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Ethanol Extract ◽  
Oxidative Status ◽  
Cholesterol Diet ◽  
Sprague Dawley ◽  
Cholesterol Levels ◽  
Sprague Dawley Rats

Gynura procumbens (Lour.) Merr. (GP) has been reported in previous studies to possess antihyperlipidaemic, antioxidative, and cardioprotective properties. This study was aimed to determine the effect of standardised 80% ethanol extract of GP on lipid profiles and oxidative status of hypercholesterolemic rats. Postmenopausal (PM) Sprague-Dawley rats were ovariectomised and fed with 2% cholesterol diet fortified with five times heated palm oil to develop hyperlipidaemia status. Two doses of the extract (250 and 500 mg/kg) and atorvastatin (10 mg/kg) were administered once daily via oral gavage for 24 weeks. Systolic blood pressure (SBP) was increased during the first month in the postmenopausal group and decreased with GP supplementation. Lipid droplets accumulation was shown at the tunica media (TM) area of the aorta in the postmenopausal group and reduced with GP supplementation. Total cholesterol (TC), total triglycerides (TG), low-density lipoprotein (LDL), and malondialdehyde (MDA) levels increased (p<0.05) at 3 and 6 months in the postmenopausal group and were reduced with GP supplementation. GP also increased high-density lipoprotein (HDL) level in the postmenopausal group. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities were reduced in the postmenopausal group compared to control in the sham group but increased (p<0.05) with GP supplementation. The results showed that the higher dose of GP (500 mg/kg) gave better effect. GP has the ability to reduce oxidative stress and prevent membrane cell damage through antioxidant enzyme activity modification and lipid profile changes in postmenopausal rats related to atherosclerosis.

scholarly journals Safety Assessment of Ubiquinol Acetate: Subchronic Toxicity and Genotoxicity Studies

2019 ◽  
Vol 2019 ◽  
pp. 1-25
Author(s):  
Gajanan Deshmukh ◽  
Suresh B. Venkataramaiah ◽  
Chandrashekar M. Doreswamy ◽  
Mohan C. Umesh ◽  
Rajesh B. Subbanna ◽  
...  
Keyword(s):  
Biologically Active ◽  
High Dose ◽  
Sprague Dawley ◽  
Subchronic Toxicity ◽  
Sprague Dawley Rats ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Endogenous Antioxidant ◽  
In Vitro Genotoxicity

Coenzyme Q10 (CoQ10) is a lipid soluble, endogenous antioxidant present at highest levels in the heart followed by the kidney and liver. The reduced CoQ10 ubiquinol is well known for its chemical instability and low bioavailability. The present study was designed to synthesize ubiquinol acetate, which is more stable and biologically active, and further evaluate its safety and genotoxic potential. Synthesized ubiquinol acetate showed better stability than that of ubiquinol at the end of 3 months. In vitro genotoxicity studies (AMES test, in vitro micronucleus and chromosomal aberration) showed ubiquinol acetate as nongenotoxic with no clastogenic or aneugenic effects at high dose of 5000 and 62.5 μg/mL, respectively. In subchronic toxicity study, ubiquinol acetate was administered orally to Sprague Dawley rats at 150, 300, and 600 mg/kg/day for 90 days. No treatment related adverse effects were observed in males at 600 mg/kg/day; however, females showed treatment related increase in AST and ALT with small focal irregular white-yellow spots in liver on gross necropsy examination. Histopathological evaluation revealed hepatocellular necrosis in high dose females which was considered as adverse. Based on the results, the No-Observed-Adverse-Effect Level (NOAEL) of ubiquinol acetate in males and females was determined as 600 and 300 mg/kg/day, respectively.

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