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

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.

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Mohammad-Sedigh Khosravi ◽  
Alireza Samimiat ◽  
Bahar Mazaheri ◽  
Farzaneh Ashrafi ◽  
Ardeshir Talebi ◽  
...  

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.


1972 ◽  
Vol 52 (1) ◽  
pp. 81-86 ◽  
Author(s):  
J. F. O’GRADY ◽  
J. P. BOWLAND

Sixty-four weanling rats were used in an experiment lasting 6 weeks to test the response of male and female rats to diets having 2.8, 3.0, 3.2, and 3.4 Mcal digestible energy (DE) per kg, where barley and wheat were used as the cereal sources and diets were supplemented with 22 IU vitamin E/kg or unsupplemented. The use of wheat or barley did not influence the performance of female rats but males utilized barley-based diets better than wheat diets and gained more in some weeks, though not overall. Male rats did not respond to vitamin E supplementation but females consumed more of the vitamin E-supplemented diets and grew 6% faster (P < 0.10). Except in the 1st week, females ate more of the lower energy than of the higher energy diets and so DE concentration did not influence rate of gain. Males were not able to adjust food intakes to compensate for dietary energy levels and needed a DE concentration of 3.2 Mcal/kg diet for maximum growth. The data indicate that there is a sex difference in growing rats insofar as DE concentration of the diet required for maximum gain is concerned.


2011 ◽  
Vol 89 (9) ◽  
pp. 623-630 ◽  
Author(s):  
Wael M. El-Sayed ◽  
Mohamed Ali Al-Kahtani

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.


2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Fatemeh Moslemi ◽  
Mehdi Nematbakhsh ◽  
Fatemeh Eshraghi-Jazi ◽  
Ardeshir Talebi ◽  
Hamid Nasri ◽  
...  

Objective. Nitric oxide (NO) has numerous important functions in the kidney. The role of NO in cisplatin (CP)-induced nephrotoxicity is not completely understood. This study was designed to determine the role of NO synthase inhibitor (L-NAME) on the severity of CP-induced nephrotoxicity in rats. Methods. Sixty four male (M) and female (F) Wistar rats were randomly divided into eight groups. The sham groups (group 1, male, n=6 and group 2, female, n=6) received saline. Groups 3 (male, n=8) and 4 (female, n=8) were treated with L-NAME (4 mg/kg, i.p.), and groups 5 (male, n=8) and 6 (female, n=8) received CP (3 mg/kg) for 7 days. Groups 7 (male, n=8) and 8 (female, n=8) were treated with L-NAME and CP for 7 days. Results. The CP-alone treated rats showed weight loss and increase in serum levels of blood urea nitrogen (BUN) and creatinine (Cr). Coadministration of L-NAME and CP did not improve weight loss, and it increased the levels of BUN and Cr in male but not in female rats (P<0.05). CP alone increased kidney damage significantly (P<0.05 ), however, the damage induced by combination of CP and L-NAME was gender-related. Conclusion. NOS inhibition by L-NAME increased CP-induced nephrotoxicity, which was gender-related.


2003 ◽  
Vol 75 (11-12) ◽  
pp. 2055-2068 ◽  
Author(s):  
M. S. Christian ◽  
N. A. Trenton

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.


1999 ◽  
Vol 161 (1) ◽  
pp. 69-75 ◽  
Author(s):  
VK Srivastava ◽  
JK Hiney ◽  
V Rettori ◽  
WL Dees

Nitric oxide (NO) has been shown to contribute to ovarian development and function. In non-ovarian tissues NO can be altered by ethanol (ETOH), a drug considered to be a gonadal toxin in men as well as male and female rats. The present study was undertaken to determine if some of the detrimental effects of chronic ETOH exposure on prepubertal ovarian function could be due to ETOH-induced alterations in the intraovarian NO system. Rats were implanted with intragastric cannulae on day 24 and began receiving control or ETOH diets on day 29. All rats were killed on day 34, determined to be in the late juvenile stage of development, and their ovaries and blood were collected. We analyzed the expression of the two constitutive forms of nitric oxide synthase (NOS), i.e. neuronal (n) NOS and endothelial (e) NOS, as well as the inducible (i) form of NOS protein in the ovaries of control and ETOH-treated rats by Western immunoblotting. Results demonstrate that eNOS protein increased markedly (P<0.02; 140 kDa) in ETOH-treated rats compared with controls. ETOH treatment did not alter the protein expression of nNOS (155 kDa) and only slightly increased that of iNOS (130 kDa). We also assessed NOS activity as determined by nitrite accumulation and by the conversion of L-[14C]arginine to L-[14C]citrulline. In this regard, the ETOH-treated animals showed an increase in ovarian nitrite generation (P<0.05), as well as an increase in ovarian citrulline formation (P<0.0001), when compared with control animals. Along with the above described ETOH-induced increases in ovarian eNOS and NO activity, the serum levels of estradiol were concomitantly suppressed (P<0.001) in the ETOH-treated rats. These results demonstrate for the first time the ETOH-induced changes in the prepubertal ovarian NO/NOS system, and suggest that these alterations contribute to the detrimental actions of the drug on prepubertal ovarian development and function.


1994 ◽  
Vol 267 (6) ◽  
pp. H2311-H2317 ◽  
Author(s):  
K. Kauser ◽  
G. M. Rubanyi

Gender differences in the production/release of endothelium-derived nitric oxide (EDNO) was assessed by determining the ability of intact endothelium to suppress serotonin- (10(-7)-10(-5) M) and phenylephrine-induced (10(-9)-(10(-5) M) contractions in thoracic aortae isolated from male and female Wistar rats mounted in organ chambers for isometric tension recording or tested in bioassay experiments. The endothelium suppressed these contractions significantly more in aortae from female than from male rats. In the bioassay, the perfusate from intact female thoracic aortic segments produced a significantly greater relaxation of the detector rings than that from the aortae isolated from male rats. Acetylcholine (10(-9)-10(-5) M), used to investigate agonist-induced release of EDNO, evoked significantly greater endothelium-dependent relaxation in aortae from female rats. The unstimulated release of 6-ketoprostaglandin F1 alpha and thromboxane B2 from intact thoracic aortic rings from male and female rats was not significantly different. There was no difference in smooth muscle reactivity to sodium nitroprusside (10(-10)-10(-6) M) in rings without endothelium. These results indicate that EDNO production/release is higher in thoracic aortae isolated from female rats.


2001 ◽  
Vol 280 (6) ◽  
pp. H2456-H2461 ◽  
Author(s):  
Yuming Wu ◽  
An Huang ◽  
Dong Sun ◽  
John R. Falck ◽  
Akos Koller ◽  
...  

Flow-induced dilation of gracilis muscle arterioles was examined in both genders of control rats and rats chronically treated with N ω-nitro-l-arginine methyl ester (l-NAME). After l-NAME treatment (4 wk), systolic blood pressure was significantly increased compared with control, whereas the plasma concentration of nitrate/nitrite was significantly reduced. Isolated and pressurized arterioles dilated significantly in response to increases in flow (0–25 μl/min). Flow-induced dilation was comparable in arterioles of control andl-NAME-treated rats but was significantly greater in female than in male rats. l-NAME + indomethacin, which abolished flow-induced dilation in arterioles of male control rats, inhibited the dilation by only ∼75% in female control rats. The residual portion of the response was eliminated by additional administration of miconazole, an inhibitor of cytochrome P-450. Indomethacin did not affect the dilation in femalel-NAME-treated rats but completely inhibited the response in male l-NAME-treated rats. The indomethacin-insensitive, flow-induced dilation in female l-NAME-treated arterioles was abolished by miconazole, 6-(2-proparglyoxyphenyl)hexanoic acid, or charybdotoxin. Thus an augmented release of endothelial prostaglandins accounts for the preserved flow-induced dilation in arterioles of male rats, whereas a metabolite of cytochrome P-450 is responsible for the maintenance of flow-induced dilation in female rats, suggesting important differences in the adaptation of the endothelium of arterioles from male and female rats to the lack of nitric oxide (NO) synthesis.


1978 ◽  
Vol 78 (3) ◽  
pp. 399-406 ◽  
Author(s):  
J. TH. J. UILENBROEK ◽  
R. TILLER ◽  
F. H. DE JONG ◽  
F. VELS

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.


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

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.


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