scholarly journals Long-Term Exposure of Psoralen and Isopsoralen Induced Hepatotoxicity and Serum Metabolites Profiles Changes in Female Rats

Metabolites ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 263 ◽  
Author(s):  
Yingli Yu ◽  
Pengli Wang ◽  
Ruili Yu ◽  
Jiaxi Lu ◽  
Miaomiao Jiang ◽  
...  

Pre-clinical safety evaluation of traditional medicines is imperative because of the universality of drug-induced adverse reactions. Psoralen and isopsoralen are the major active molecules and quality-control components of a traditional herbal medicine which is popularly used in Asia, Fructus Psoraleae. The purpose of this study is to assess the long-term effects of psoralen and isopsoralen with low levels on the biochemical parameters and metabolic profiles of rats. Three doses (14, 28, and 56 mg/kg) of psoralen and one dose (28 mg/kg) of isopsoralen were administered to rats over 12 weeks. Blood and selected tissue samples were collected and analyzed for hematology, serum biochemistry, and histopathology. Metabolic changes in serum samples were detected via proton nuclear magnetic resonance (1H-NMR) spectroscopy. We found that psoralen significantly changed the visceral coefficients, blood biochemical parameters, and histopathology, and isopsoralen extra influenced the hematological index. Moreover, psoralen induced remarkable elevations of forvaline, isoleucine, isobutyrate, alanine, acetone, pyruvate, glutamine, citrate, unsaturated lipids, choline, creatine, phenylalanine, and 4-hydroxybenzoate, and significant reductions of ethanol and dimethyl sulfone. Isopsoralen only induced a few remarkable changes of metabolites. These results suggest that chronic exposure to low-level of psoralen causes a disturbance in alanine metabolism, glutamate metabolism, urea cycle, glucose-alanine cycle, ammonia recycling, glycine, and serine metabolism pathways. Psoralen and isopsoralen showed different toxicity characteristics to the rats.

2013 ◽  
Vol 26 (3) ◽  
pp. 161-169 ◽  
Author(s):  
Daniela Dimer Leffa ◽  
Adriani Paganini Damiani ◽  
Daiane Dal Col Damazio ◽  
Naiana Pereira Guerra ◽  
Morgana Moretti ◽  
...  

ObjectiveThis study investigated the influence of ageing – in particular the decrease of gonadal hormone levels during the ageing process – on the memory and the levels of DNA damage in the hippocampus of female rats.MethodsThree groups of female Wistar rats were investigated: Group I consisted of non-ovariectomised, adult animals (6 months old); Group II consisted of non-ovariectomised, aged animals (18 months old); and Group III consisted of ovariectomised, aged animals (18 months old). The memory of the animals in these groups was examined via novel object recognition and inhibitory avoidance tests. The hippocampus tissue samples of all animals were obtained via biopsy and used to quantify the DNA damage using a Comet Assay.ResultsAccording to our findings, the process of ageing results in a change during the behavioural tests. To prevent genotoxic damage to the hippocampus caused by the ageing process, lowered hormone levels seem to be part of a protective biochemical mechanism in the body of rats. Animals that were previously submitted to an ovariectomy adapted better to these lower levels of hormones.ConclusionOur results indicate that ovariectomy can provide beneficial long-term effects on the memory. However, this could be specific to the kind of memory examined, as the aversive memory deficits caused by ageing were not affected by ovariectomy.


2021 ◽  
Vol 22 (16) ◽  
pp. 8899
Author(s):  
Marina Gabaglio ◽  
Erica Zamberletti ◽  
Cristina Manenti ◽  
Daniela Parolaro ◽  
Tiziana Rubino

Cannabis is the most-used recreational drug worldwide, with a high prevalence of use among adolescents. In animal models, long-term adverse effects were reported following chronic adolescent exposure to the main psychotomimetic component of the plant, delta-9-tetrahydrocannabinol (THC). However, these studies investigated the effects of pure THC, without taking into account other cannabinoids present in the cannabis plant. Interestingly, cannabidiol (CBD) content seems to mitigate some of the side effects of THC, at least in adult animals. Thus, in female rats, we evaluated the long-term consequences of a co-administration of THC and CBD at a 3:1 ratio, chosen based on the analysis of recently confiscated illegal cannabis samples in Europe. CBD content is able to mitigate some of the long-term behavioral alterations induced by adolescent THC exposure as well as long-term changes in CB1 receptor and microglia activation in the prefrontal cortex (PFC). We also investigated, for the first time, possible long-term effects of chronic administration of a THC/CBD combination reminiscent of “light cannabis” (CBD:THC in a 33:1 ratio; total THC 0.3%). Repeated administration of this CBD:THC combination has long-term adverse effects on cognition and leads to anhedonia. Concomitantly, it boosts Glutamic Acid Decarboxylase-67 (GAD67) levels in the PFC, suggesting a possible lasting effect on GABAergic neurotransmission.


1976 ◽  
Vol 71 (1) ◽  
pp. 109-114 ◽  
Author(s):  
I. DONIACH ◽  
D. J. SHALE

SUMMARY From the differences in radiation profiles between 131I and 125I isotopes of iodine it would be expected that they would show different effects on thyroid function. The differences should lead to lower rates of thyroid gland destruction with 125I and hence less post-irradiation hypothyroidism. This difference in biological effect has been demonstrated in rats by indirect assessment of thyroid function. In this report the long-term effects of a range of similar doses of 131I and 125I were compared, in male and female rats, by direct assessment of thyroid function. Seventeen months after receiving 25 and 125 μCi of 131I, male and female rats showed significant elevation of serum TSH concentration and a reduction in 3 h radioiodine uptake. Rats receiving 1 and 5 μCi of 131I and all doses of 125I showed no significant changes in thyroid function. These findings confirm the previously reported differences in effect between the 131I and 125I isotopes of iodine in the rat.


2001 ◽  
Vol 74 (3) ◽  
pp. 321-328 ◽  
Author(s):  
Anne Buison ◽  
Frank Ordiz ◽  
K.-L.Catherine Jen

2012 ◽  
Vol 66 (6) ◽  
pp. 602-609 ◽  
Author(s):  
A. D. Anastasilakis ◽  
S. A. Polyzos ◽  
S. Delaroudis ◽  
K. A. Toulis ◽  
S. Mandanas ◽  
...  

Lipids ◽  
1985 ◽  
Vol 20 (10) ◽  
pp. 668-674 ◽  
Author(s):  
M. S. Thomassen ◽  
J. Norseth ◽  
E. N. Christiansen

2014 ◽  
Vol 33 (12) ◽  
pp. 1241-1252 ◽  
Author(s):  
A Zafiropoulos ◽  
K Tsarouhas ◽  
C Tsitsimpikou ◽  
P Fragkiadaki ◽  
I Germanakis ◽  
...  

Lethal cardiac complications leading to death and various arrhythmias have been reported after organophosphate and/or carbamate poisonings. The present study focuses on the long-term effects of repeated low-level exposure to diazinon, propoxur, and chlorpyrifos (CPF) on cardiac function in rabbits. The yearly based experimental scheme of exposure consisted of two oral administration periods, lasting 3 months and 1 month each, interrupted by an 8-month washout period (total duration 12 months). At the end of the experimental scheme, the rabbits underwent an echocardiographic evaluation under sedation, after which they were killed and the tissue and serum samples were collected. A mild localized cardiotoxic effect was established by echocardiography for the three pesticides tested. Severe histological alterations were identified, especially in the diazinon-treated animals in agreement with increased persistence of this pesticide established in the cardiac tissue. In addition, all pesticides tested increased the oxidative stress and oxidative modifications in the genomic DNA content of the cardiac tissues, each one following a distinct mechanism.


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