The Obesogenic Potency of Various High-Caloric Diet Compositions in Male Rats, and Their Effects on Expression of Liver and Kidney Proteins Involved in Drug Elimination

2017 ◽  
Vol 106 (6) ◽  
pp. 1650-1658 ◽  
Author(s):  
Ali Abdussalam ◽  
Osama H. Elshenawy ◽  
Yousef A. bin Jardan ◽  
Ayman O.S. El-Kadi ◽  
Dion R. Brocks
2021 ◽  
pp. 096032712199190
Author(s):  
AA Dar ◽  
A Fehaid ◽  
S Alkhatani ◽  
S Alarifi ◽  
WS Alqahtani ◽  
...  

Methotrexate (MTX) is frequently used drug in treatment of cancer and autoimmune diseases. Unfortunately, MTX has many side effects including the hepato-renal toxicity. In this study, we hypothesized that Luteolin (Lut) exhibits protective effect against the MTX-induced hepato-renal toxicity. In order to investigate our hypothesis, the experiment was designed to examine the effect of exposure of male rats to MTX (20 mg/kg, i.p., at day 9) alone or together with Lut (50 mg/kg, oral for 14 days) compared to the control rats (received saline). The findings demonstrated that MTX treatment induced significant increases in the liver and kidney functions markers in serum samples including Aspartate transaminase (AST), Alanine transaminase (ALT), creatinine, urea and uric acid. MTX also mediated an oxidative stress expressed by elevated malondialdehyde (MDA) level and decreased level of reduced glutathione (GSH), antioxidant enzyme activities, and downregulation of the Nrf2 gene expression as an antioxidant trigger. Moreover, the inflammatory markers (NF-κB, TNF-α, and IL-1β) were significantly elevated upon MTX treatment. In addition, MTX showed an apoptotic response mediated by elevating the pro-apoptotic (Bax) and lowering the anti-apoptotic (Bcl-2) proteins. All of these changes were confirmed by the observed alterations in the histopathological examination of the hepatic and renal tissues. Lut exposure significantly reversed all the MTX-induced changes in the measured parameters suggesting its potential protective role against the MTX-induced toxicity. Finally, our findings concluded the antioxidative, anti-inflammatory and anti-apoptotic effects of Lut as a mechanism of its protective role against the MTX-induced hepato-renal toxicity in rats.


2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Javier Morán-Martínez ◽  
Roberto Beltrán del Río-Parra ◽  
Nadia Denys Betancourt-Martínez ◽  
Rubén García-Garza ◽  
Joel Jiménez-Villarreal ◽  
...  

For the EPD, different voltages and different times were used. Male rats were used in four groups (n=3) with different treatments. The blood sample was obtained for genotoxic analysis and liver and kidney organs were removed for histopathological analysis. The amount of NPs TiO2 deposited on the samples of the arches increases gradually in the times of 15 and 30 s. At all voltages, however, at 45, 60, 75, and 90 s, there is an increase up to 25 V. Cell viability in lymphocytes treated with TiO2 NPs did not cause genotoxicity. In the histopathological findings of hepatic and renal tissue, nuclear alterations and necrosis were observed. The objective of the study was to improve the physical and biocompatibility characteristics of the NiTi arches for which the EPD is used. The technique for the deposition of TiO2 NPs was used, where this technique could be used as an economical and versatile way to perform homogeneous depositions even on surfaces with the complexity of the NiTi alloy. As for genotoxicity and cytotoxicity, we continue to have controversial results.


2012 ◽  
Vol 63 (4) ◽  
pp. 417-427 ◽  
Author(s):  
Mariana Tozlovanu ◽  
Delphine Canadas ◽  
Annie Pfohl-Leszkowicz ◽  
Christine Frenette ◽  
Robert J. Paugh ◽  
...  

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


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Murtala Akanji Abdullahi ◽  
Elijah Oladapo Oyinloye ◽  
Akinyinka Alabi ◽  
Aderonke Adeyinka Aderinola ◽  
Luqman Opeyemi Ogunjimi ◽  
...  

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.


2017 ◽  
Vol 2 (2) ◽  
pp. 112-120
Author(s):  
Nazar Mohammed Shareef Mahmood ◽  
Sarkawt Hamad Ameen Hamad ◽  
Dlshad Hussein Hassan ◽  
Karwan Ismael Othman

The toxicity of lead acetate (L. A.) concerned to public health disruptor due to its persistence in the environment and it has the adverse influence on the human and animal health as well. It causes physiological,biochemical, and neurological dysfunctions in humans. Histologically it has a negative effect on the liver which is considered one of the major target organs where acts as detoxification machine by elimination the toxic substance from the blood in rich with it.  As well as it affects kidneys that are the two of the most filtering organs. Therefore the present study was aimed to investigate the histopathological effect of L.A. on liver and kidney tissues in male rats. Twenty male rats involved in the study were equally and randomly divided into two groups each of them involved 10 animals. Group I (castrated rats) and Group II (control) each group received 80mg/L of lead acetate dissolved in one liter distilled water by drinking for 15 days. Histological sections showed some alterations including abnormal architecture, cell degeneration, nuclear degeneration, hyperchromatic hepatocytes, immune cells, degeneration in tubules, dilation in sinusoids, dilation in central vein of liver increased bowman's space glomerular atrophy degeneration of tubular cells in liver and kidney tissues of rats in castrated rats from control group. But the size of degenerated tissue was more severe in castrated male rats. It was concluded that the castration process could produce a hypogonadism and decreased testosterone which owns many receptors in kidney and liver may produce adverse influence with L.A. administration.


Author(s):  
Majd Almakhatreh ◽  
Ezar Hafez ◽  
Ehab Tousson ◽  
Ahmed Masoud

Aims: Etoposide (Vepesid) is chemotherapeutic drugs that inhibit topoisomerase II activity and long been used for treatment of human malignancies, where it is a semi-synthetic compound derived from the plant Podophyllum peltatum. The current study was designed to investigate the possible protective effect of rosemary extract against Etoposide -induced changes in liver and kidney functions, and DNA damage in rats. Materials and Methods: A total of 50 male Wistar albino rats were divided randomly into four groups (1st group was control; 2nd group was treated with rosemary, 3rd group was received etoposide, and 4th & 5th groups was co- and post treated groups respectively). Results: The administration of Etoposide revealed a significant increase in serum ALT, AST, ALP, creatinine, urea, potassium ions, chloride ions, and DNA damage. In contrast; a significant decrease in albumen, total proteins, sodium ions, and calcium ions were when compared with control group. This increased in ALT, AST, ALP, creatinine, urea, potassium ions, chloride ions, and DNA damage was reduced after administration of rosemary when co-treated with etoposide (G4), or post-treated after etoposide  (G5) for four weeks with lowest damage in G4. Also, this decreased in albumen, total proteins, sodium ions, and calcium ions was increased after administration of rosemary when co-treated with etoposide (G4), or post-treated after etoposide (G5) for four weeks with lowest damage in G4. Conclusion: It could be concluded that rosemary has a promising role and it worth to be considered as a natural substance for protective the liver and kidney toxicity induced by etoposide (Vepesid) chemotherapy.


1974 ◽  
Vol 142 (2) ◽  
pp. 273-277 ◽  
Author(s):  
Jan-Åke Gustafsson ◽  
Åke Pousette

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).


1993 ◽  
Vol 27 (11) ◽  
pp. 1383-1388 ◽  
Author(s):  
Peter Gal ◽  
Jamie T. Gilman

OBJECTIVE: To review the literature on the physiologic changes created by neonatal patent ductus arteriosus (PDA) and the potential impact on drug disposition in these infants. DATA SOURCES: An Index Medicus and bibliographic search of the English-language literature pertaining to neonatal PDA and drug usage in newborns. DATA SYNTHESIS: PDA in premature infants is associated with a variety of physiologic changes that could alter drug disposition. Perfusion of drug-elimination organs (i.e., liver and kidney) may be diminished, resulting in decreased drug elimination. Further, the general fluid overload state associated with PDA may result in larger volumes of distribution (Vd), and dilutional effects for many drugs. Drug absorption, Vd, tissue penetration, and clearance may be affected by the physiologic changes incurred by a PDA. Although the pharmacokinetics of several categories of therapeutic agents may be affected by a PDA, disposition changes with the aminoglycosides and indomethacin have been the best documented. The most reliable pharmacokinetic change appears to be related to drug Vd. The interpretation of many of these studies is confounded by a potential drug interaction with the concurrent administration of indomethacin for PDA closure. CONCLUSIONS: Close therapeutic drug monitoring is indicated in newborns with PDAs as abrupt changes in drug disposition can occur with PDA closure. PDA-induced changes in specific pharmacokinetic parameters of agents such as the aminoglycosides, indomethacin, and perhaps vancomycin may prove to be a valuable diagnostic adjunct for the identification of babies with undiagnosed PDA. More research into this pharmacophysiologic aspect of pharmacokinetics is warranted.


2019 ◽  
Vol 14 (1) ◽  
pp. 7 ◽  
Author(s):  
MedhatM Menshawy ◽  
WalidM Sharaf ◽  
RehamS.E. Esmail ◽  
AbdelR.H. Farrag

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