A Biochemical and Immunological Investigation into the Physiological Basis of the Increased Albumin Filtration Induced in Hyperalbuminaemic Female Wistar Rats

1. The level of proteinuria induced in female Wistar rats after bovine albumin injection intraperitoneally was highly dose dependent. 2. The proteinuria remained highly selective, with albumin constituting approximately 90% of the total protein excreted, even in the most severely affected rats. 3. Calculations relating the amount of bovine albumin available in the serum for filtration to the amount excreted in the urine indicated that complete saturation of the reticuloendothelial and tubular protein reabsorption systems-5-have occurred during the course of the 5 day injection period in rats given more than 3.5 mg of bovine albumin day−1 g−1 body wt. 4. When this situation was attained there appeared to be no further increase in glomerular permeability to either rat or bovine albumin and an equilibrium state seemed to exist where, when serum albumin levels were raised above the normal level, all the excess albumin passed across the glomerular filter to be excreted in the urine. 5. The passage of these large quantities of albumin across the glomerular filter-5-have resulted not from ultrastructural damage to the filter itself but rather from the generation of vastly increased concentration gradients across the glomerular basement membrane, which were sufficiently large to overcome the electrostatic repulsive forces which normally severely restrict albumin filtration.

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Effect of sodium (S)-2-hydroxyglutarate in male, and succinic acid in female Wistar rats against renal ischemia-reperfusion injury, suggesting a role of the HIF-1 pathway

PeerJ ◽

10.7717/peerj.9438 ◽

2020 ◽

Vol 8 ◽

pp. e9438

Author(s):

Eduardo Cienfuegos-Pecina ◽

Tannya R. Ibarra-Rivera ◽

Alma L. Saucedo ◽

Luis A. Ramírez-Martínez ◽

Deanna Esquivel-Figueroa ◽

...

Keyword(s):

Oxidative Stress ◽

Succinic Acid ◽

Wistar Rats ◽

Ischemia Reperfusion ◽

The Other ◽

Oxidative Stress Biomarkers ◽

Stress Biomarkers ◽

Female Wistar Rats ◽

Dose Dependent ◽

Nephroprotective Effect

Background Ischemia–reperfusion (IR) injury is the main cause of delayed graft function in solid organ transplantation. Hypoxia-inducible factors (HIFs) control the expression of genes related to preconditioning against IR injury. During normoxia, HIF-α subunits are marked for degradation by the egg-laying defective nine homolog (EGLN) family of prolyl-4-hydroxylases. The inhibition of EGLN stabilizes HIFs and protects against IR injury. The aim of this study was to determine whether the EGLN inhibitors sodium (S)-2-hydroxyglutarate [(S)-2HG] and succinic acid (SA) have a nephroprotective effect against renal IR injury in Wistar rats. Methods (S)-2HG was synthesized in a 22.96% yield from commercially available L-glutamic acid in a two-step methodology (diazotization/alkaline hydrolysis), and its structure was confirmed by nuclear magnetic resonance and polarimetry. SA was acquired commercially. (S)-2HG and SA were independently evaluated in male and female Wistar rats respectively after renal IR injury. Rats were divided into the following groups: sham (SH), nontoxicity [(S)-2HG: 12.5 or 25 mg/kg; SA: 12.5, 25, or 50 mg/kg], IR, and compound+IR [(S)-2HG: 12.5 or 25 mg/kg; SA: 12.5, 25, or 50 mg/kg]; independent SH and IR groups were used for each assessed compound. Markers of kidney injury (BUN, creatinine, glucose, and uric acid) and liver function (ALT, AST, ALP, LDH, serum proteins, and albumin), proinflammatory cytokines (IL-1β, IL-6, and TNF-α), oxidative stress biomarkers (malondialdehyde and superoxide dismutase), and histological parameters (tubular necrosis, acidophilic casts, and vascular congestion) were assessed. Tissue HIF-1α was measured by ELISA and Western blot, and the expression of Hmox1 was assessed by RT-qPCR. Results (S)-2HG had a dose-dependent nephroprotective effect, as evidenced by a significant reduction in the changes in the BUN, creatinine, ALP, AST, and LDH levels compared with the IR group. Tissue HIF-1α was only increased in the IR group compared to SH; however, (S)-2HG caused a significant increase in the expression of Hmox1, suggesting an early accumulation of HIF-1α in the (S)-2HG-treated groups. There were no significant effects on the other biomarkers. SA did not show a nephroprotective effect; the only changes were a decrease in creatinine level at 12.5 mg/kg and increased IR injury at 50 mg/kg. There were no effects on the other biochemical, proinflammatory, or oxidative stress biomarkers. Conclusion None of the compounds were hepatotoxic at the tested doses. (S)-2HG showed a dose-dependent nephroprotective effect at the evaluated doses, which involved an increase in the expression of Hmox1, suggesting stabilization of HIF-1α. SA did not show a nephroprotective effect but tended to increase IR injury when given at high doses.

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Prolonged oestrogen treatment does not correlate with a sustained increase in anterior pituitary mitotic index in ovariectomized Wistar rats

Journal of Endocrinology ◽

10.1677/joe-08-0474 ◽

2008 ◽

Vol 200 (3) ◽

pp. 301-309 ◽

Cited By ~ 9

Author(s):

L A Nolan ◽

A Levy

Keyword(s):

Mitotic Activity ◽

Mitotic Index ◽

Anterior Pituitary ◽

Wistar Rats ◽

High Dose ◽

Oestrogen Treatment ◽

Female Wistar Rats ◽

Continuous Dose ◽

Wet Weight ◽

Dose Dependent

Oestrogen is a powerful mitogen that is believed to exert a continuous, dose-dependent trophic stimulus at the anterior pituitary. This persistent mitotic effect contrasts with corticosterone and testosterone, changes in the levels of which induce only transient, self-limiting fluctuations in pituitary mitotic activity. To further define the putative long-term trophic effects of oestrogen, we have accurately analysed the effects of 7 and 28 days oestrogen treatment on anterior pituitary mitotic activity in ovariectomized 10-week-old Wistar rats using both bromodeoxyuridine (BrdU) and timed colchicine-induced mitotic arrest. An oestrogen dose-dependent increase in mitotic index was seen 7 days after the start of treatment as expected, representing an acceleration in gross mitotic activity from 1.7%/day in ovariectomized animals in the absence of any oestrogen replacement to 3.7%/day in the presence of a pharmacological dose of oestrogen (50 mcg/rat per day: ∼230 mcg/kg per day). Despite continued exposure to high-dose oestrogen and persistence of the increase in pituitary wet weight, the increase in mitotic index was unexpectedly not sustained. After 28 days of high-dose oestrogen treatment, anterior pituitary mitotic index and BrdU-labelling index were not significantly different from baseline. Although a powerful pituitary mitogen in the short term, responsible, presumably, for increased trophic variability in oestrus cycling females, these data indicate that in keeping with other trophic stimuli to the pituitary and in contrast to a much established dogma, the mitotic response to longer-term high-dose oestrogen exposure is transient and is not the driver of persistent pituitary growth, at least in female Wistar rats.

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ANTIFERTILITY ACTIVITY AND CONTRACEPTIVE POTENTIAL OF THE HYDROALCOHOLIC RHIZOME EXTRACT OF TRILLIUM GOVANIANUM IN FEMALE WISTAR RATS

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i11.27420 ◽

2018 ◽

Vol 11 (11) ◽

pp. 329

Author(s):

Shivam Sharma ◽

Vineet Mehta ◽

Parul Sharma ◽

Kritika Jaggi ◽

Malairaman Udayabanu ◽

...

Keyword(s):

Wistar Rats ◽

Herbal Remedy ◽

Elevated Serum ◽

Morphological Alterations ◽

Estrogenic Potential ◽

Endometrial Thickening ◽

Female Wistar Rats ◽

Implantation Sites ◽

Trillium Govanianum ◽

Dose Dependent

Objective: Trillium govanianum is used in several traditional containing steroids and sex hormones for the management of inflammation, menstrual disorders, sex-related disorders, and antiseptic. The present study was aimed to investigate the antifertility potential of hydroalcoholic rhizome extract of T. govanianum and to explore the possible mechanism of action. Methods: Anti-implantation activity of T. govanianum rhizome extract (125 and 250 mg/kg; p.o.) was performed in female Wistar rats with proven fertility, and its estrogenic/antiestrogenic effect was evaluated in ovariectomized females. 17-α-ethinylestradiol (1 μg/rat/day; s.c.) or plant extract was administered for 11 days after which animals were sacrificed. Percentage inhibition of implantation sites, serum estrogen levels, changes in body and uterus weight, and morphological alterations in the uterus and ovaries were evaluated. Results: T. govanianum treatment resulted in increased uterus weight and induced dose-dependent anti-implantation effect, with 100% implantation inhibition at 250 mg/kg dose. Anti-implantation effects of T. govanianum were associated with endometrial thickening and significantly elevated serum estrogen levels. Moreover, estrogenic/antiestrogenic studies revealed that T. govanianum possessed strong estrogenic effect; however, the effect was saturable. Conclusion: T. govanianum possesses antifertility activity which can be attributed to its strong estrogenic potential and uterine thickening. Moreover, it could find a clinical application as a safer and efficacious birth control herbal remedy.

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Post-somatostatin rebound secretion of growth hormone is dependent on growth hormone-releasing factor in unrestrained female rats

Journal of Endocrinology ◽

10.1677/joe.0.1220583 ◽

1989 ◽

Vol 122 (2) ◽

pp. 583-591 ◽

Cited By ~ 26

Author(s):

H. Sugihara ◽

S. Minami ◽

I. Wakabayashi

Keyword(s):

Growth Hormone ◽

Adult Female ◽

Wistar Rats ◽

Bolus Injection ◽

Female Rats ◽

Dependent Manner ◽

Gh Secretion ◽

Female Wistar Rats ◽

Plasma Gh ◽

Dose Dependent

ABSTRACT To examine the characteristics of GH secretion following the termination of the infusion of somatostatin, unrestrained adult female Wistar rats were subjected to repeated infusions of somatostatin separated by 30-min control periods. When somatostatin was infused for 150 min at a dose of 3, 30 or 300 μg/kg body wt per h, the magnitude of the rebound GH secretion increased in a dose-dependent manner. The infusion of somatostatin at a dose of 300 μg/kg body wt per h for 60, 150 or 240 min progressively augmented the size of the rebound GH secretion. When an antiserum to rat GH-releasing factor (GRF) was injected i.v. 10 min before the end of the infusion, the peak amplitude of the rebound GH secretion (300 μg/kg body wt, 150 min) was reduced to less than 20% of that of control rats. The rebound GH secretion (300 μg/kg body wt per h, 150 min) was augmented by a bolus injection of human GRF (1 μg/kg body wt). The combined effect of the end of infusion of somatostatin and a bolus injection of GRF on the amount of GH secreted was additive. The plasma GH response to GRF was completely inhibited when human GRF (3 μg/kg body wt per h) and somatostatin (300 μg/kg body wt per h) were infused simultaneously for 150 min. The magnitude of the rebound GH secretion following the termination of the co-administration was larger than that following the somatostatin infusion alone, but this rebound was not enhanced by a bolus injection of human GRF. Moreover, the amount of GH secreted was significantly less than that after the termination of somatostatin infusion plus a bolus injection of human GRF in the absence of preceding GRF administration. These results suggest that at least part of the influence of somatostatin on GH secretion is exerted at the level of the hypothalamus through modulating the release of GRF. In addition, it is inferred that the simultaneous infusion of GRF and somatostatin induces the attenuation of the GH response to GRF through a receptor effect. Journal of Endocrinology (1989) 122, 583–591

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Methylphenidate and Alprazolam Co-Abuse: Drug-DNA Interactions

10.20944/preprints202010.0481.v1 ◽

2020 ◽

Author(s):

Shweta Sharma ◽

Meenu Dutt ◽

Neha Sharma ◽

Ravinder Naik Dharavath ◽

Tanzeer Kaur

Keyword(s):

Wistar Rats ◽

Spectroscopic Methods ◽

Dependent Manner ◽

Dna Interactions ◽

Spectral Changes ◽

Spectral Peaks ◽

Female Wistar Rats ◽

Ft Ir ◽

Dose Dependent ◽

Insight Into

Drug abuse is a major issue worldwide. Methylphenidate (MPH) and alprazolam (ALZ) are commonly prescribed drugs for the treatment of ADHD and anxiety disorders, respectively. The limited studies suggest that abusers primarily use benzodiazepines to counteract adverse effects associated with methylphenidate usage. The main aim of this study was to investigate the interaction of drugs with DNA using spectroscopic methods. Female Wistar rats were administered with MPH (10, 20, 40 mg/kg) and ALZ (5, 10, 20 mg/kg) alone and in combination for a period of 28 days. The FT-IR and UV results reveal some spectral changes in a dose-dependent manner, which indicates interactions of drugs with DNA. Thus, the changes in spectral peaks provide some insight into the mechanism of the interaction of drugs with DNA.

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Adverse Effects of Sub-lethal Doses of Chlorpyrifos on Birth Outcome of Female Wistar Rats

Journal of Applied Life Sciences International ◽

10.9734/jalsi/2020/v23i830177 ◽

2020 ◽

pp. 1-6

Author(s):

J. U. I. Iheanacho ◽

P. I. K. Onyeka ◽

H. I. Udujih ◽

O. G. Udujih ◽

U. W. Dozie

Keyword(s):

Wistar Rats ◽

Birth Outcome ◽

Organophosphorus Pesticide ◽

Dependent Manner ◽

Treatment Groups ◽

Increased Risk ◽

Female Wistar Rats ◽

Group 2 ◽

Dose Dependent Decrease ◽

Dose Dependent

Chlorpyrifos is a widely used Organophosphorus pesticide for pest control, leading to increased risk for humans and wildlife exposure. The aim of the present study was to determine the effects of chlorpyrifos on birth outcome in pregnant female wistar rats (Rattus novergicus). Animals were randomly assigned into 4 equal groups, group 1 were untreated and served as control. Rats of group 2 to 4 were treated with chlorpyrifos at concentration 0.2%, 0.4% and 0.8% respectively through feed and drinking water ad libitum from gestation day 1 through to weaning. The results on litter size indicates non-significant dose dependent decrease (p>0.05) across treated groups. Total litter birth weight significantly decreased (p<0.05) in a dose dependent manner compared with control. Stillbirth recorded non-significant (p>0.05) among treatment groups when compared with that of control. Also, postnatal survival showed significant (p<0.05) dose dependent lower number of pups survival between parturition and weaning. These results demonstrated that Chlorpyrifos has adverse impact on birth outcome in treated rats.

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Clomiphene citrate impairs the endometrial CD98 expression in ovariectomized and non-ovariectomized rats: Role of HCG

International Journal of Reproductive BioMedicine ◽

10.18502/ijrm.v17i6.4809 ◽

2019 ◽

Author(s):

Behpour Yousefi ◽

Elnaz Rahbar

Keyword(s):

Wistar Rats ◽

Clomiphene Citrate ◽

Ovariectomized Rats ◽

Control Group ◽

Expression Levels ◽

Immunohistochemistry Staining ◽

Female Wistar Rats ◽

Dose Dependent ◽

Lower Expression

Background: Clomiphene citrate (CC) is one of the widely used drugs as an ovulation stimulant, but its adverse effects on the endometrium results in lowering down the pregnancy rate. Endometrium CD98 is also important in the process of implantation. Objective: To evaluate the immunohistochemistry expression levels of endometrial CD98 following injection of CC with and without Human chorionic gonadotropin (HCG) in ovariectomized and non-ovariectomized rats. Materials and Methods: Seventy two (12-14 wk old) female Wistar rats were randomly divided into two groups (n = 36): (a) ovariectomized and (b) non-ovariectomized. Each group was further divided into six subgroups (n = 6/each): (1) CC 10 mg/kg, (2) CC 20 mg/kg, (3) HCG, (4) CC 10 mg/kg with HCG, (5) CC 20 mg/kg with HCG, and (6) control. The experimental subgroups received a single dose of CC (daily, five days) and HCG (after the last injection of CC) alone or in combination. Immunohistochemistry staining was performed on paraffin-embedded endometrial tissues to evaluate the expression levels of CD98. Result: Animals undergoing ovariectomy presented a significantly lower expression level of endometrial CD98 (p < 0.001) when compared with non-ovariectomized in the same condition that groups were subdivided. There was also a dose-dependent reduction (p < 0.001) in the expression of CD98 in non-ovariectomized subgroups when compared with control group. In addition, injection of HCG following treatment with CC improved its expression. Conclusion: It was concluded that CC impairs CD98 expression in endometrium and this impairment is intensified with the removal of the ovary. Also, an injection of HCG following treatment with CC can slightly improve the expression of CD98.

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ANTI-ESTROGENIC PROPERTIES OF ETHANOLIC LEAF EXTRACT OF BOERHAVIA DIFFUSA ON FEMALE WISTAR RATS.

10.1055/s-0037-1608549 ◽

2017 ◽

Author(s):

C Olajide Omolola ◽

J Okpuzor ◽

I Nnadozie Jane ◽

R Adewole Adeniyi

Keyword(s):

Wistar Rats ◽

Leaf Extract ◽

Female Wistar Rats ◽

Estrogenic Properties ◽

Ethanolic Leaf Extract ◽

Boerhavia Diffusa

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NEW DATA CONCERNING THE ROLE PLAYED BY PROGESTERONE IN THE CONTROL OF FOLLICULAR GROWTH IN THE RAT

Acta Endocrinologica ◽

10.1530/acta.0.0750569 ◽

1974 ◽

Vol 75 (3) ◽

pp. 569-578 ◽

Cited By ~ 29

Author(s):

G. Buffler ◽

S. Roser

Keyword(s):

Wistar Rats ◽

Venous Blood ◽

Oestrous Cycle ◽

Female Rats ◽

Cycle Duration ◽

Follicular Growth ◽

The Third ◽

Female Wistar Rats

ABSTRACT The mechanisms involved in the prolongation of the oestrous cycle following LH administration were studied in 4-day cyclic female Wistar rats. In females injected with LH on the morning of dioestrus I there was an increase in ovarian venous blood progesterone as compared with non-injected animals. In both LH-treated females, and those injected with progesterone on the morning of dioestrus I, a slowing up in follicular growth was observed from the afternoon of dioestrus I. The size of follicles greater than 400 urn present in LH or progesterone injected animals on the third day of cycle was similar to the size reached by the same range of follicles in non-injected animals on the second day of the cycle. Hence, the increase in endogenous ovarian progesterone elicited by LH was considered as the cause of the slowing up of follicular growth and therefore of the lengthening of the oestrous cycle duration in female rats injected with LH at the beginning of 4-day cycle.

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