Potential adverse effects of oseltamivir in rats: males are more vulnerable than females

2011 ◽  
Vol 89 (9) ◽  
pp. 623-630 ◽  
Author(s):  
Wael M. El-Sayed ◽  
Mohamed Ali Al-Kahtani
Keyword(s):  
Adverse Effects ◽  
Protein Profile ◽  
Antiviral Drug ◽  
Thioredoxin Reductase ◽  
Serum Levels ◽  
Female Rats ◽  
Male Rats ◽  
Glutathione S Transferase ◽  
Quinone Oxidoreductase ◽  
Male And Female Rats

Oseltamivir is the most widely used antiviral drug for the treatment and prophylaxis of influenza. However, not much is known about its adverse effects. The potential side effects were investigated in male and female rats (140–170 g). Oseltamivir was administered at 2.2 mg·kg–1·day–1 for 5 days. For both genders, treatment with oseltamivir resulted in significant reductions in the hepatic activities of glutathione reductase, glutathione peroxidase, and glutathione S-transferase. Also for both genders, oseltamivir produced modest reductions in the hepatic activities of UDP-glucuronosyltransferase, quinone oxidoreductase, thioredoxin reductase, CYP1A1/2, and CYP3A, as well as hepatic glutathione content. For both genders, neither the kidney functions nor protein profile was affected by oseltamivir. Oseltamivir also caused significant elevation in serum levels of both triacylglycerols and LDL-cholesterol and in the activity of γ-glutamyl transpeptidase, in both genders. For male animals only, oseltamivir treatment elevated the serum level of total cholesterol as well as the activity of serum alanine aminotransferase, and reduced the hepatic activities of superoxide dismutase and catalase. Oseltamivir caused oxidative stress and acute toxicity in the liver, and disrupted the cholesterol and lipid metabolism but was less likely to cause serious drug interactions. There was a sexual differentiation in these adverse effects, with adverse effects being more evident in male rats.

scholarly journals Hydration with Mannitol and Dextrose May Promote Cisplatin-Induced Nephrotoxicity: Test of Five Protocols of Hydration during Cisplatin Therapy in Rat Models

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Mohammad-Sedigh Khosravi ◽  
Alireza Samimiat ◽  
Bahar Mazaheri ◽  
Farzaneh Ashrafi ◽  
Ardeshir Talebi ◽  
...  
Keyword(s):  
Tumor Therapy ◽  
Kidney Tissue ◽  
Serum Levels ◽  
Female Rats ◽  
Male Rats ◽  
Male And Female ◽  
Male And Female Rats ◽  
Female Wistar Rats ◽  
Solid Tumor Therapy ◽  
Cisplatin Therapy

Backgrounds. Cisplatin (CP) still is a novel choice for solid tumor therapy, but it is accompanied with the side effect of nephrotoxicity. Hydration may reduce the risk of CP-induced nephrotoxicity, while the issue is still challenging. In this study, five types of hydration protocols including saline, mannitol, dextrose saline, saline plus furosemide, and saline plus mannitol were examined in both sexes of rats during CP therapy. Methods. Seventy-six male and female Wistar rats in 14 groups of experiments were subjected to CP therapy, and five types of hydration protocols were implemented, and the induced nephrotoxicity was evaluated via biochemical markers, kidney function parameters, and pathology investigation. Results. Male and female rats had different responses to hydration protocol types. The higher mortality rate was seen in female rats that received mannitol or dextrose hydration types. In addition, the serum levels of blood urea nitrogen (BUN) and creatinine (Cr) and sodium excretion fraction (ENa%) increased and the clearance of Cr (ClCr) decreased significantly ( P < 0.05 ) in female rats hydrated with saline plus furosemide or mannitol plus saline-treated groups. The worsened condition in male rats is observed in the mannitol hydration group with a significant decrease of ClCr and significant increase of serum BUN and Cr and ENa% ( P < 0.05 ). The higher kidney tissue damage score (KTDS) in the mentioned groups verified the findings. Conclusion. Hydration with mannitol or dextrose promotes the risk of nephrotoxicity during CP therapy with more intensity on the female.

Evaluation of thyroid function in neonatal and adult rats: The neglected endocrine mode of action

2003 ◽  
Vol 75 (11-12) ◽  
pp. 2055-2068 ◽  
Author(s):  
M. S. Christian ◽  
N. A. Trenton
Keyword(s):  
Metabolic Rate ◽  
Thyroid Function ◽  
Critical Period ◽  
Serum Levels ◽  
Thyroid Stimulating Hormone ◽  
Female Rats ◽  
Male Rats ◽  
Adult Rats ◽  
Male And Female Rats ◽  
Serum Tsh

Although known to regulate growth and development, cellular metabolism, the use of oxygen, and basal metabolic rate, thyroid hormones have been only minimally evaluated in neonatal rodents at critical times of development. Despite some modulation of metabolic rate by other hormones, such as testosterone, growth hormone, and norepinephrine, 3,5,3'-triiodothyronine (T3) and 3,5,3',5'-tetraiodothyronine (T4) are the most important metabolic rate modulators. Endpoints used for thyroid function assessment in neonatal and adult rats include thyroid-stimulating hormone (TSH), T3, and T4 levels and histopathology. In rodents, decreased serum levels of T3 and T4 and increased serum TSH levels, with sustained release of TSH and resultant follicular cell hypertrophy/hyperplasia, are typical hormonal and histopathological findings attributable to compounds altering thyroid function. Hypothyroidism early in the neonatal period can affect reproductive endpoints in both male and female rats, with the critical period of exposure being the first two weeks postnatal. Hypothyroidism has been shown to reduce gonadotrophin levels and delay pubertal spermatogenesis in male rats and to block gonadotropin-induced first ovulation in immature female rats by decreasing FSH and luteinizing hormone (LH) serum concentrations. Inclusion of evaluations of TSH, T3, and T4 assays in multigeneration and developmental neurotoxicity protocols may assist in risk assessments.

scholarly journals Activities of Antioxidant and Detoxifying Enzymes in Rats after Lead Exposure

2008 ◽  
Vol 77 (3) ◽  
pp. 347-354 ◽  
Author(s):  
M. A. Alghazal ◽  
V. Lenártová ◽  
K. Holovská ◽  
A. Sobeková ◽  
M. Falis ◽  
...  
Keyword(s):  
Thiobarbituric Acid ◽  
Female Rats ◽  
Male Rats ◽  
Glutathione S Transferase ◽  
Sod Activity ◽  
Compensatory Response ◽  
Male And Female ◽  
Male And Female Rats ◽  
Enzyme Superoxide Dismutase ◽  
Gst Activity

The studies were undertaken to investigate the activity response of the antioxidant enzyme superoxide dismutase (SOD) and detoxifying enzyme glutathione-S-transferase (GST) of rats exposed to lead. Enzyme activities were determined in the liver, kidneys and heart of male and female rats that received 100 mg and 1000 mg of lead acetate per litre, respectively, in their drinking water for 18 weeks. Statistical analyses indicated differences related to the organs and to the sex of animals. Administration of lead evoked an increase of the SOD activity in the liver and kidneys both in male and female rats but only in the heart of female rats. GST activity decreased in the liver and heart of male rats, while this activity increased in the liver and heart of female rats. In kidneys, the lower lead dose resulted in a decrease of the GST activity in both groups but the higher dose evoked an increase of activity only in male rats. Thiobarbituric acid reactive substances (TBARS), an indicator of oxidative stress, significantly increased in rats that were given the high lead dose, in the kidneys of male rats and in the heart of female rats. Most probably, the observed changes could be a compensatory response to different lead accumulation in the male and female organs and also the possible distinct mechanisms in ROS elimination.

SPECIFIC SUPPRESSION OF FOLLICLE-STIMULATING HORMONE SECRETION IN GONADECTOMIZED MALE AND FEMALE RATS WITH INTRASPLENIC OVARIAN TRANSPLANTS

1978 ◽  
Vol 78 (3) ◽  
pp. 399-406 ◽  
Author(s):  
J. TH. J. UILENBROEK ◽  
R. TILLER ◽  
F. H. DE JONG ◽  
F. VELS
Keyword(s):  
Hormone Secretion ◽  
Serum Levels ◽  
Female Rats ◽  
Male Rats ◽  
Vaginal Smears ◽  
Intact Male ◽  
Male And Female ◽  
Kidney Capsule ◽  
Specific Suppression ◽  
Male And Female Rats

Adult male and female rats received an ovarian homotransplant under the kidney capsule or in the spleen 14 days after gonadectomy. After transplantation under the kidney capsule, the high levels of both LH and FSH normally observed after gonadectomy decreased to the levels found in intact male and female rats. After transplantation into the spleen, however, the serum levels of LH increased still further, although a decrease was observed in the level of FSH. In male rats, the concentrations of oestradiol-17β in the plasma increased from 17 to 56 pg/ml after transplantation of an ovary under the kidney capsule; the concentration was not increased after intrasplenic ovarian transplantation. In female rats with an intrasplenic transplant, the uterine weight did not increase and vaginal smears were not cornified. Administration of oestrogen and progesterone to produce approximately the concentrations found in rats with an intrasplenic transplant did not result in decreased concentrations of FSH. These results suggest that the ovary secretes a substance with specific FSH-suppressing activity, which is not inactivated by the liver.

SERUM CONCENTRATIONS OF TESTOSTERONE, OESTROGENS, LUTEINIZING HORMONE AND FOLLICLE-STIMULATING HORMONE IN MALE AND FEMALE RATS DURING THE CRITICAL PERIOD OF NEURAL SEXUAL DIFFERENTIATION

1979 ◽  
Vol 80 (1) ◽  
pp. 103-110 ◽  
Author(s):  
S. F. PANG ◽  
A. R. CAGGIULA ◽  
V. L. GAY ◽  
R. L. GOODMAN ◽  
C. S. F. PANG
Keyword(s):  
Post Partum ◽  
Serum Levels ◽  
Female Rats ◽  
Male Rats ◽  
Female Rat ◽  
Serum Concentrations ◽  
Male And Female ◽  
Rat Pups ◽  
Male And Female Rats ◽  
Sampling Times

Untreated male and female rat pups were killed 1–5 days post partum and the serum concentrations of testosterone, oestrogens, LH and FSH were determined by radioimmunoassay. At all five sampling times, the serum concentrations of testosterone in male rats were about three times higher than those in female rats, but serum levels of oestrogens did not differ between the sexes. Serum concentrations of LH and FSH were lower in male than in female pups. In another study, rats were decapitated 1–10 days after birth and serum concentrations of testosterone were determined with a different radioimmunoassay. Again, at all four sampling times, the concentration of testosterone was significantly higher in the male than in the female pups.

RESULTS OF RADIOIMMUNOASSAYS OF RAT PITUITARY AND SERUM PROLACTIN AFTER ADRENALECTOMY AND PERPHENAZINE TREATMENT IN RATS

1971 ◽  
Vol 50 (4) ◽  
pp. 599-606 ◽  
Author(s):  
M. BEN-DAVID ◽  
A. DANON ◽  
R. BENVENISTE ◽  
C. P. WELLER ◽  
F. G. SULMAN
Keyword(s):  
Serum Levels ◽  
High Serum ◽  
Target Organ ◽  
Female Rats ◽  
Male Rats ◽  
Serum Prolactin ◽  
Male And Female Rats ◽  
Rat Pituitary ◽  
Prolactin Content ◽  
Intact Rats

SUMMARY Treatment for 5 days of female rats with perphenazine (5 mg/kg/day) induced full lobulo—alveolar differentiation. Long-standing adrenalectomy (12 days) decreased this mammotrophic effect of perphenazine. The mechanism of this reaction was studied in male rats in order to avoid fluctuations of the prolactin content in the anterior pituitary. Adult male rats were adrenalectomized and injected s.c. after 12 days with perphenazine (10 mg/kg). Two hours later the rats were killed and pituitary and serum prolactin levels assayed by double antibody radioimmunoassay. In intact rats, perphenazine treatment enhanced serum prolactin up to 104 ± 4 (s.e.m.) ng/ml (± 350%). Adrenalectomy alone increased serum prolactin from 30± 5 to 47 ± 6 ng/ml (+56%), and augmented the perphenazine-induced release of prolactin from the pituitary into the blood from 104 ± 4 to 147 ± 10 ng/ml (+ 42%). In chronically adrenalectomized adult female rats extremely high amounts of prolactin (+ 1617%) were detected in the serum at the end of 5 days' treatment with perphenazine (5 mg/kg/day). These results indicate that removal of the adrenals in male and female rats does not interfere with the ability of the pituitary to secrete prolactin. Moreover, they also show that in adrenalectomized rats the impaired mammotrophic effect of perphenazine is not due to prolactin deficiency (since high serum levels of this hormone were present) but to the absence of corticosteroids at the target organ.

scholarly journals Growth hormone- and testosterone-dependent regulation of glutathione transferase subunit A5 in rat liver

1998 ◽  
Vol 332 (3) ◽  
pp. 763-768 ◽  
Author(s):  
Louise STAFFAS ◽  
Elizabeth M. ELLIS ◽  
John D. HAYES ◽  
Bo LUNDGREN ◽  
Joseph W. DePIERRE ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Rat Liver ◽  
Hormonal Regulation ◽  
Glutathione Transferase ◽  
Affinity Purification ◽  
Young Male ◽  
Female Rats ◽  
Male Rats ◽  
Glutathione S Transferase ◽  
Male And Female Rats

The class Alpha glutathione S-transferase (GST) subunit A5 is expressed in the livers of young male and female rats. After sexual maturation, this protein is no longer detectable in the livers of male rats, but is still expressed in female rats. We have previously demonstrated that the sexually dimorphic secretion of growth hormone regulates the levels of certain class Mu GSTs in rat liver, and this study was designed to investigate the hormonal regulation of GSTA5. Control and hypophysectomized rats of both sexes were used to study the role of growth hormone in the regulation of hepatic GSTA5; and the influence of testosterone on the expression of this same subunit was investigated in intact females and castrated males. Liver cytosols were subjected to SDS/PAGE and immunoblotting using antibodies directed towards rat (r)GSTA5, and to affinity purification on glutathione–Sepharose followed by reverse-phase HPLC in order to quantify the relative levels of rGSTA1, A2, A3, A4, M1 and M2 subunits. These analyses revealed that the expression of rGSTA5 is, indeed, regulated by both growth hormone and testosterone.

scholarly journals Sex-Related Difference in Nitric Oxide Metabolites Levels after Nephroprotectant Supplementation Administration against Cisplatin-Induced Nephrotoxicity in Wistar Rat Model: The Role of Vitamin E, Erythropoietin, or N-Acetylcysteine

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Mehdi Nematbakhsh ◽  
Zahra Pezeshki
Keyword(s):  
Nitric Oxide ◽  
Vitamin E ◽  
Wistar Rat ◽  
Serum Levels ◽  
Female Rats ◽  
Male Rats ◽  
Recombinant Erythropoietin ◽  
Human Recombinant Erythropoietin ◽  
Male And Female Rats ◽  
Nitric Oxide Metabolites

Background. Nitric oxide (NO) concentration in serum is altered by cisplatin (CP), and NO influences CP-induced nephrotoxicity. The effect of nephroprotectant agent supplementation (vitamin E, human recombinant erythropoietin (EPO), or n-acetylcysteine (NAC)) on the NO metabolites levels after CP administration in the two genders was determined. Methods. Sixty-four adult Wistar rats were randomly divided into 10 groups. Male and female rats in different groups received vehicle (saline), CP (7 mg/kg) alone, CP plus EPO (100 IU/kg), CP plus vitamin E (250 mg/kg), and CP plus NAC (600 mg/kg). CP was administrated as a single dose, but the supplementations were given for a period of 7 days. Results. In male rats, the serum levels of total NO metabolites (NOx) and nitrite were increased significantly (P<0.05) by CP. However, vitamin E significantly reduced the serum levels of these metabolites, which was increased by administration of CP (P<0.05), and such findings were not observed for female rats. The EPO or NAC did not influence NO metabolites neither in male rats nor in female rats. Conclusion. Although vitamin E, EPO, and NAC are reported to be nephroprotectant agents against CP-induced nephrotoxicity, only vitamin E could reduce the level of all NO metabolites only in male rats.

SEX DIFFERENCE IN THE INDUCTION OF LACTOGENIC RECEPTORS IN RAT LIVERS

1979 ◽  
Vol 92 (3) ◽  
pp. 532-541 ◽  
Author(s):  
Nobuaki Furuhashi ◽  
Victor S. Fang
Keyword(s):  
Binding Sites ◽  
Specific Binding ◽  
Elevated Serum ◽  
Serum Testosterone ◽  
Serum Levels ◽  
Significant Negative Correlation ◽  
Female Rats ◽  
Male Rats ◽  
Affinity Constant ◽  
Male And Female Rats

ABSTRACT The relationship between serum levels of growth hormone (rGH), prolactin (rPRL), lutenizing hormone (rLH), follicle-stimulating hormone (rFSH), corticosterone, oestrogen, (oestradiol-17β) and testosterone and the hepatic binding sites specific to [125I]human-prolactin (h-PRL) were investigated in normal rats, in rats bearing the GH- and PRL-secreting tumour (GH3), and in rats 14 days after tumour removal. The presence of GH3 tumour elevated serum levels of rGH and rPRL and concomitantly increased the hepatic binding of [125I] h-PRL; the male rats had a greater increase than the female rats. The increased binding was due to an increase in the specific membrane binding sites, whereas the affinity constant (Ka) was not changed. In both male and female rats, there was a significant positive correlation between serum rGH levels (P < 0.001) or serum rPRL (P < 0.02) and specific binding of [1251] h-PRL in female rats only (P < 0.02). In male rats, there was a significant negative correlation between serum testosterone levels and specific bindings of [125I]h-PRL (P < 0.05). These results suggest that rGH and rPRL regulates the hepatic h-PRL receptors in female rats, and testosterone predominantly inhibits the induction of the hepatic lactogenic receptors in male rats.

Effects of the new prolactin-producing tumour 7315b on gonadotrophin secretion in adult male and female rats

1989 ◽  
Vol 120 (2) ◽  
pp. 261-268 ◽  
Author(s):  
A. Kooy ◽  
R. F. A. Weber ◽  
M. P. Ooms ◽  
J. T. M. Vreeburg
Keyword(s):  
Serum Levels ◽  
Female Rats ◽  
Male Rats ◽  
Suitable Model ◽  
Intact Male ◽  
Adult Rats ◽  
Male And Female ◽  
Male And Female Rats ◽  
Serum Lh ◽  
Gonadotrophin Secretion

ABSTRACT The effects of the transplantable purely prolactin-secreting tumour 7315b on serum gonadotrophins were studied in adult rats. Possible contributions of the adrenals to the tumour-induced inhibition of serum LH and FSH were evaluated. The suppressive actions of tumour 7315b on serum gonadotrophins in gonadectomized plus adrenalectomized male and female rats were compared. Within 4 weeks after inoculation of tumour 7315b in intact male rats very high levels of prolactin and decreased serum levels of gonadotrophins and testosterone were recorded. At autopsy reduced weights of testes and accessory sex organs and slightly increased adrenal weights were found. In addition, in animals treated with a small testosterone-filled capsule after castration, tumour 7315b reduced serum concentrations of LH and FSH. Adrenalectomy did not prevent this suppressive action of the tumour on the post-castration rise of serum gonadotrophins. Suppression of serum gonadotrophins during hyperprolactinaemia was greater in gonadectomized plus adrenalectomized female rats than in male rats, indicating that the degree of the tumour-induced suppression of LH and FSH after castration is determined to a large extent by the sex of the animal. The purely prolactin-secreting tumour 7315b has therefore been shown to be a suitable model for studying the effects of severe hyperprolactinaemia on the pituitary-gonadal axis in rats. Journal of Endocrinology (1989) 120, 261–268

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