scholarly journals Unusual responses of rat hepatic and renal peroxisomes to RMI 14, 514, a new hypolipidemic agent.

1978 ◽  
Vol 78 (3) ◽  
pp. 810-822 ◽  
Author(s):  
D J Svoboda
Keyword(s):  
Female Rats ◽  
Urate Oxidase ◽  
Male Rats ◽  
Ultrastructural Changes ◽  
Male Rat ◽  
Acid Oxidase ◽  
Amino Acid Oxidase ◽  
Hypolipidemic Agents ◽  
Hypolipidemic Agent ◽  
Liver And Kidney

RMI 14, 514 ([5-tetradecycloxy]-2-furancarboxylic acid) represents a new class of hypolipidemic agents which cause unusual ultrastructural changes in liver of male rats and in selected peroxisomal enzymes in liver and kidney of both sexes. Among the principal ultrastructural changes in peroxisomes of male rat liver were (a) cavitation and compartmentalization of the matrix, often giving the appearance of a peroxisome-within-a-peroxisome, and (b) narrow, dense extensions of canaliculi or cisterns from the periphery of the peroxisome, forming partial circlets or surrounding irregular areas of cytoplasm. The unusual enzyme responses were (a) elevation of catalase activity in liver and kidney in female rats, (b) increased activity of three hydrogen peroxide-producing oxidases (urate oxidase, L-alpha-hydroxy acid oxidase, and D-amino acid oxidase) in the liver of both sexes, and (c) elevation of activity of the last two oxidases in male kidney. The peculiar ultrastructural changes in liver peroxisomes combined with the responses of selected peroxisomal enzymes represent unusual modulations or adaptations of these organelles to a hypolipidemic agent, the effects of which have not been reported extensively.

scholarly journals Sex-, tissue-, and exposure duration-dependent effects of imidacloprid modulated by piperonyl butoxide and menadione in rats. Part I: oxidative and neurotoxic potentials

2014 ◽  
Vol 65 (4) ◽  
pp. 387-398 ◽  
Author(s):  
Mustafa Yardimci ◽  
Yusuf Sevgiler ◽  
Eyyup Rencuzogullari ◽  
Mehmet Arslan ◽  
Mehmet Buyukleyla ◽  
...  
Keyword(s):  
Cholinesterase Activity ◽  
Specific Effect ◽  
Piperonyl Butoxide ◽  
Female Rats ◽  
Male Rats ◽  
Male Rat ◽  
Total Protein Content ◽  
Sprague Dawley ◽  
Adverse Action ◽  
Liver And Kidney

Abstract Earlier research has evidenced the oxidative and neurotoxic potential of imidacloprid, a neonicotinoid insecticide, in different animal species. The primary aim of this study was to determine how metabolic modulators piperonyl butoxide and menadione affect imidacloprid’s adverse action in the liver and kidney of Sprague-Dawley rats of both sexes. The animals were exposed to imidacloprid alone (170 mg kg-1) or in combination with piperonyl butoxide (100 mg kg-1) or menadione (25 mg kg-1) for 12 and 24 h. Their liver and kidney homogenates were analysed spectrophotometrically for glutathione peroxidase, glutathione S-transferase, catalase, total cholinesterase specific activities, total glutathione, total protein content, and lipid peroxidation levels. Imidacloprid displayed its prooxidative and neurotoxic effects predominantly in the kidney of male rats after 24 h of exposure. Our findings suggest that the observed differences in prooxidative and neurotoxic potential of imidacloprid could be related to differences in its metabolism between the sexes. Co-exposure (90-min pre-treatment) with piperonyl butoxide or menadione revealed tissue-specific effect of imidacloprid on total cholinesterase activity. Increased cholinesterase activity in the kidney could be an adaptive response to imidacloprid-induced oxidative stress. In the male rat liver, co-exposure with piperonyl butoxide or menadione exacerbated imidacloprid toxicity. In female rats, imidacloprid+menadione co-exposure caused prooxidative effects, while no such effects were observed with imidacloprid alone or menadione alone. In conclusion, sex-, tissue-, and duration-specific effects of imidacloprid are remarkable points in its toxicity

Subacute co-exposure to low doses of ruthenium(III) changes the distribution, excretion and biological effects of silver ions in rats

2020 ◽  
Vol 17 (2) ◽  
pp. 163 ◽  
Author(s):  
Nicoleta Vedeanu ◽  
Cezara Voica ◽  
Dana Alina Magdas ◽  
Bela Kiss ◽  
Maria-Georgia Stefan ◽  
...  
Keyword(s):  
Biological Effects ◽  
Female Rats ◽  
Male Rats ◽  
Male Rat ◽  
Human Organism ◽  
Critical Element ◽  
Female Rat ◽  
Low Doses ◽  
Subacute Toxicity ◽  
Liver And Kidney

Environmental contextAlthough ruthenium is a technology-critical element used in several new industries, little is known about its environmental impact or possible human health risks. We report a toxicological evaluation of laboratory animals during co-exposure to ruthenium and silver. We identified interactions between the two elements that could lead to unwanted biological effects. AbstractRuthenium is one of the rarest metals on Earth that is classified as a technology-critical element (TCE). Silver, however, is well known for its antibacterial and immunostimulant properties. The increasing use of Ru and Ag in medicine and daily life makes simultaneous exposure possible, with unknown pharmacokinetic or toxicological consequences for the human organism. Thus, the present study investigated the influence of co-exposure to RuIII on the subacute toxicity of Ag ions in rats after repeated daily administration for 28 days of low doses by oral gavage. The subacute toxicity was investigated by the evaluation of several biochemical and hematological parameters, evaluation of specific oxidative stress biomarkers from liver and kidney, and histopathological investigation of liver and kidney tissue samples after 28 days of exposure in female rats. In addition, Ag and Ru concentrations were determined by inductively coupled plasma mass spectrometry (ICP-MS) in urine, liver and kidney parenchyma in male rats. The obtained results showed that co-exposure to low doses of RuIII and Ag did not produce any significant biochemical, hematological or histopathological alterations in the treated female rat groups, except for an increased red cell distribution width (RDW) value. A decrease of urinary excretion of Ag and of the Ag concentration in kidneys was observed in the male rat group co-exposed to RuIII and Ag. This is the first invivo study investigating the toxic effect of co-exposure to low doses of Ag and Ru ions, and the obtained results may justify further research on this subject, mainly on the investigation of possible competitive mechanisms.

scholarly journals Spinal mechanisms contributing to the development of pain hypersensitivity induced by sphingolipids in the rat

2021 ◽  
Author(s):  
Hong Wei ◽  
Zuyue Chen ◽  
Ari Koivisto ◽  
Antti Pertovaara
Keyword(s):  
Amino Acid ◽  
Nmda Receptors ◽  
Receptor Antagonist ◽  
Gap Junction ◽  
Male Rats ◽  
Acid Oxidase ◽  
Amino Acid Oxidase ◽  
Mk 801 ◽  
Mechanical Hypersensitivity ◽  
Pain Hypersensitivity

Abstract Background Earlier studies show that endogenous sphingolipids can induce pain hypersensitivity, activation of spinal astrocytes, release of proinflammatory cytokines and activation of TRPM3 channel. Here we studied whether the development of pain hypersensitivity induced by sphingolipids in the spinal cord can be prevented by pharmacological inhibition of potential downstream mechanisms that we hypothesized to include TRPM3, σ1 and NMDA receptors, gap junctions and D-amino acid oxidase. Methods Experiments were performed in adult male rats with a chronic intrathecal catheter for spinal drug administrations. Mechanical nociception was assessed with monofilaments and heat nociception with radiant heat. N,N-dimethylsphingosine (DMS) was administered to induce pain hypersensitivity. Ononetin, isosakuranetin, naringenin (TRPM3 antagonists), BD-1047 (σ1 receptor antagonist), carbenoxolone (a gap junction decoupler), MK-801 (NMDA receptor antagonist) and AS-057278 (inhibitor of D-amino acid oxidase, DAAO) were used to prevent the DMS-induced hypersensitivity, and pregnenolone sulphate (TRPM3 agonist) to recapitulate hypersensitivity. Results DMS alone produced within 15 min a dose-related mechanical hypersensitivity that lasted at least 24 h, without effect on heat nociception. Preemptive treatments with ononetin, isosakuranetin, naringenin, BD-1047, carbenoxolone, MK-801 or AS-057278 attenuated the development of the DMS-induced hypersensitivity, but had no effects when administered alone. Pregnenolone sulphate (TRPM3 agonist) alone induced a dose-related mechanical hypersensitivity that was prevented by ononetin, isosakuranetin and naringenin. Conclusions Among spinal pronociceptive mechanisms activated by DMS are TRPM3, gap junction coupling, the σ1 and NMDA receptors, and DAAO.

scholarly journals Increased bioactivation of dihaloalkanes in rat liver due to induction of class Theta glutathione S-transferase T1-1

1998 ◽  
Vol 335 (3) ◽  
pp. 619-630 ◽  
Author(s):  
Philip J. SHERRATT ◽  
Margaret M. MANSON ◽  
Anne M. THOMSON ◽  
Erna A. M. HISSINK ◽  
Gordon E. NEAL ◽  
...  
Keyword(s):  
Western Blotting ◽  
Rat Liver ◽  
Female Rats ◽  
Male Rats ◽  
Male Rat ◽  
Female Rat ◽  
Glutathione S Transferase ◽  
Chemopreventive Agents ◽  
Cytoplasmic Staining ◽  
Potent Inducer

A characteristic feature of the class Theta glutathione S-transferase (GST) T1-1 is its ability to activate dichloromethane and dibromoethane by catalysing the formation of mutagenic conjugates. The level of the GSTT1 subunit within tissues is an important determinant of susceptibility to the carcinogenic effects of these dihaloalkanes. In the present study it is demonstrated that hepatic GST activity towards these compounds can be elevated significantly in female and male Fischer-344 rats by feeding these animals on diets supplemented with cancer chemopreventive agents. Immunoblotting experiments showed that increased activity towards the dihaloalkanes is associated with elevated levels of the GSTT1 subunit in rat liver. Sex-specific effects were observed in the induction of GSTT1 protein. Amongst the chemopreventive agents tested, indole-3-carbinol proved to be the most potent inducer of hepatic GSTT1 in male rats (6.2-fold), whereas coumarin was the most potent inducer of this subunit in the livers of female rats (3.5-fold). Phenobarbital showed significant induction of GSTT1 only in male rat liver and had little effect in female rat liver. Western blotting showed that class Alpha, Mu and Pi GST subunits are not co-ordinately induced with GSTT1, indicating that the expression of GSTT1 is determined, at least in part, by mechanisms distinct from those that regulate levels of other transferases. The increase in amount of hepatic GSTT1 protein was also reflected by an increase in the steady-state level of mRNA in response to treatment with chemopreventive agents and model inducers. Immunohistochemical detection of GSTT1 in rat liver supported the Western blotting data, but showed, in addition to cytoplasmic staining, significant nuclear localization of the enzyme in hepatocytes from some treated animals, including those fed on an oltipraz-containing diet. Significantly, the hepatic level of cytochrome P-450 2E1, an enzyme which offers a detoxification pathway for dihaloalkanes, was unchanged by the various inducing agents studied. It is concluded that the induction of GSTT1 by dietary components and its localization within cells are important factors that should be considered when assessing the risk dihaloalkanes pose to human health.

scholarly journals Glutathione Conjugates of Ochratoxin a as Biomarkers of Exposure / Glutationski Konjugati Okratoksina A Kao Biomarkeri Izloženosti

2012 ◽  
Vol 63 (4) ◽  
pp. 417-427 ◽  
Author(s):  
Mariana Tozlovanu ◽  
Delphine Canadas ◽  
Annie Pfohl-Leszkowicz ◽  
Christine Frenette ◽  
Robert J. Paugh ◽  
...  
Keyword(s):  
Ochratoxin A ◽  
Rat Kidney ◽  
Female Rats ◽  
Amide Bond ◽  
Male Rats ◽  
Dark Agouti ◽  
Female Rat ◽  
Male And Female ◽  
Male And Female Rats ◽  
Liver And Kidney

AbstractIn the present study the photoreactivity of the fungal carcinogen ochratoxin A (OTA) has been utilised to generate authentic samples of reduced glutathione (GSH) and N-acetylcysteine (NAC) conjugates of the parent toxin. These conjugates, along with the nontoxic OTα, which is generated through hydrolysis of the amide bond of OTA by carboxypeptidase A, were utilised as biomarkers to study the metabolism of OTA in the liver and kidney of male and female Dark Agouti rats. Male rats are more susceptible than female rats to OTA carcinogenesis with the kidney being the target organ. Our studies show that the distribution of OTA in male and female rat kidney is not significantly different. However, the extent of OTA metabolism was greater in male than female rats. Much higher levels of OTα were detected in the liver compared to the kidney, and formation of OTα is a detoxification pathway for OTA. These findings suggest that differences in metabolism between male and female rats could provide an explanation for the higher sensitivity of male rats to OTA toxicity

Toxicological evaluation of hydroethanol leaf extract of Pupalia lappacea (Linn.) Juss. (Amaranthaceae) in rodents

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Murtala Akanji Abdullahi ◽  
Elijah Oladapo Oyinloye ◽  
Akinyinka Alabi ◽  
Aderonke Adeyinka Aderinola ◽  
Luqman Opeyemi Ogunjimi ◽  
...  
Keyword(s):  
Leaf Extract ◽  
Density Lipoprotein ◽  
Serum Testosterone ◽  
Female Rats ◽  
Male Rats ◽  
Laboratory Animals ◽  
Serum Testosterone Level ◽  
Control Group ◽  
Toxicological Evaluation ◽  
Liver And Kidney

Abstract Objectives Several studies have established the ethnobotanical benefits of Pupalia lappacea (PL) in laboratory animals without extensive toxicological evaluation of its safety profiles. Thus, an extensive toxicological investigation of sub-chronic oral administration of the hydroethanol leaf extract of P. lappacea in rodents was carried out in this study. Methods Different groups of rats were treated orally with the extract (10, 50 and 250 mg/kg) daily for 90 consecutive days. The control group received distilled water (10 mL/kg). After 90 days, some rats were left for additional 30 days without treatment for reversibility study. Blood and organs samples were collected for different evaluations at the end of study periods. Results The extract decreased the bodyweights, feeding and water intakes in female rats. PL increased the weights of the liver and kidney in male rats. PL increased the red blood cell (RBC), packed cell volume (PCV), hemoglobin (Hb), triglycerides (TRIG), cholesterol and high density lipoprotein (HDL) contents in rats. PL (250 mg/kg) significantly reduced the sperm motility and serum testosterone level. Cyto-architectural distortions of the testes, liver and spleen were visible. Conclusions The findings showed that P. lappacea is relatively safe at lower doses but cautions should be taken at higher dose.

scholarly journals EFFECT OF YOHIMBINE ON CLOMIPRAMINE-INDUCED SEXUAL DYSFUNCTION IN MALE RATS

2017 ◽  
Vol 10 (2) ◽  
pp. 92
Author(s):  
Devangam Sheshadri Shekar
Keyword(s):  
Sexual Behavior ◽  
Sexual Dysfunction ◽  
Histopathological Examination ◽  
Red Light ◽  
Female Rats ◽  
Male Rats ◽  
Male Rat ◽  
Testicular Damage

Object: The present investigation has been carried out to find out the effect of yohimbine on clomipramine-induced sexual dysfunction in male rats.Methods: The male rats were treated with clomipramine and yohimbine simultaneously for 60 days. During the treatment, all the male rats werechallenged with the female rats which are in estrous phase and their sexual behavior was observed under dim red light. Half of the animals in each group and remaining on 60 day were sacrificed, blood was collected and serum separated. Testis was collected and preserved in 10% formalin forsubsequent histopathological examination. thResults: The study reveals that yohimbine failed to antagonize the clomipramine-induced sexual dysfunction in male rats in all aspects, except thepartial improvement in the sexual behavior.Conclusion: Yohimbine a well-known aphrodisiac failed to antagonize the clomipramine-induced sexual dysfunction in male rats. The decrease intestosterone levels, a decrease in spermatozoa count were continued even in the presence of yohimbine except improvement in the sexual behaviorparameters. Hence, yohimbine could not be a safe antidote against clomipramine-induced sexual dysfunction in male rats.Keywords: Yohimbine, Clomipramine, Testosterone, Male rat sexual competence, Testicular damage.

scholarly journals Different mechanisms of regulation of nuclear reduced nicotinamide–adenine dinucleotide phosphate-dependent 3-oxo steroid 5α-reductase activity in rat liver, kidney and prostate

1974 ◽  
Vol 142 (2) ◽  
pp. 273-277 ◽  
Author(s):  
Jan-Åke Gustafsson ◽  
Åke Pousette
Keyword(s):  
Testosterone Propionate ◽  
Reductase Activity ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Female Rats ◽  
Male Rats ◽  
Regulatory Mechanisms ◽  
Oestradiol Benzoate ◽  
Liver And Kidney ◽  
Reduced Nicotinamide Adenine Dinucleotide ◽  
Hydroxy Steroid

The regulatory mechanisms involved in the control of the nuclear NADPH-dependent 3-ketosteroid 5α-reductase (5α-reductase) activity were studied in liver, kidney and prostate. The substrate used was [1,2-3H]androst-4-ene-3,17-dione (androstenedione) (for liver and kidney) or [4-14C]androstenedione (for prostate). The hepatic nuclear 5α-reductase activity was greater in female than in male rats, was greater in adult than in prepubertal female rats, increased after castration of male rats, but was not affected by treatment with testosterone propionate or oestradiol benzoate. These regulatory characteristics are in part different from those previously described for the hepatic microsomal 5α-reductase. The renal nuclear metabolism of androstenedione, i.e. 5α reduction and 17β-hydroxy steroid reduction, was relatively unaffected by sex, age, castration and treatment with testosterone propionate. However, treatment of castrated male rats with oestradiol benzoate led to a significant increase in the 5α-reductase activity and a significant decrease in the 17β-hydroxy steroid reductase activity. Finally, the nuclear 5α-reductase activity in prostate was androgen-dependent, decreasing after castration and increasing after treatment with testosterone propionate. In conclusion, the nuclear 5α-reductase activities in liver, kidney and prostate seem to be under the control of distinctly different regulatory mechanisms. The hypothesis is presented that whereas the prostatic nuclear 5α-reductase participates in the formation of a physiologically active androgen, 5α-dihydrotestosterone, this may not be the true function of the nuclear 5α-reductase in liver and kidney. These enzymes might rather serve to protect the androgen target sites in the chromatin from active androgens (e.g. testosterone) by transforming them into less active androgens (e.g. 5α-androstane-3,17-dione and/or 5α-dihydrotestosterone).

Effects of acute administration of 2-hydroxylated metabolites of oestrogens on LH and prolactin secretion in male and female prepubertal rats

1984 ◽  
Vol 103 (3) ◽  
pp. 317-325
Author(s):  
A. K. Brar ◽  
G. Fink
Keyword(s):  
Plasma Concentration ◽  
Female Rats ◽  
Male Rats ◽  
Male Rat ◽  
Female Rat ◽  
Uterine Weight ◽  
Immature Female ◽  
Male And Female ◽  
Immature Male ◽  
Lh Release

ABSTRACT The effects of catechol oestradiol and catechol oestrone on the release of LH and prolactin were investigated in immature male and female Wistar rats. In male rats both catechol oestradiol and catechol oestrone significantly increased the plasma concentration of LH, and catechol oestradiol but not catechol oestrone significantly increased the plasma concentration of prolactin and decreased the pituitary concentration of LH. The parent oestrogens, oestradiol-17β and oestrone, had no effect on plasma LH concentrations, but both increased significantly the plasma concentration of prolactin, and oestrone but not oestradiol-17β increased the pituitary concentration of LH. In immature female rats, catechol oestradiol inhibited the surge of LH and the increase in uterine weight induced by injecting pregnant mare serum gonadotrophin (PMSG). The injection of oestrone induced an increase in the plasma concentration of LH which was about nine times greater than that produced by oestradiol-17β. There were no significant differences in the effects of these steroids on plasma prolactin concentration. These results (i) confirm that in the immature male rat catechol oestrogens can stimulate LH release and show that catechol oestradiol can increase prolactin release, (ii) show that catechol oestradiol can inhibit the stimulatory effects of PMSG on LH release and uterine weight in the immature female rat, and (iii) demonstrate that oestrone can stimulate LH release in the immature female rat. J. Endocr. (1984) 103, 317-325

Cytoplasmic estrogen, but not progestin, binding sites in male rat adipose tissues

1980 ◽  
Vol 239 (4) ◽  
pp. E237-E237
Keyword(s):  
Binding Sites ◽  
Specific Binding ◽  
Estradiol Benzoate ◽  
Female Rats ◽  
Male Rats ◽  
Male Rat ◽  
Adipose Tissues ◽  
Body Fat Content ◽  
Estrogen Binding ◽  
Fat Pads

Male rat adipose tissues contain cytoplasmic estrogen binding sites comparable to those found in females. This bindng is of high affinity (Kd = 1.7 x 10(-10) M) and is estrogen specific. Binding of 17 beta-estradiol was inhibited by radioinert estrogens (17 beta-estradiol and R 2858) but not by other steroids (progesterone, 5 alpha-dihydrotestosterone, and corticosterone). Estrogen binding sites were found in all fat pads studied, but levels were highest in the epididymal pads. Treatment of female rats with 17 beta-estradiol benzoate (E2B) induced cytoplasmic progestin receptors in adipose tissues, but in three separate experiments, E2B treatment (20 microgram/day for 3 days) failed to induce measurable progestin ([3H]R 5020) binding sites in males. E2B treatment reduced lipoprotein lipase (LPL) activity by approximately 75% in epididymal (male) and parametrial (female) fat pads. Concurrent progesterone treatment increased parametrial LPL activity in E2B-treated females, but progesterone had no effect on epididymal fat pad LPL activity in males. These findings are consistent with the hypothesis that in male rats aromatized (estrogenic) metabolites of testosterone may reduce body fat content and alter lipid metabolism by direct actions on adipose tissues.

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