Effect of fluoxetine treatment on neurotoxicity induced by lysolecithin in male rats

Author(s):  
Elham Gholami ◽  
Mohammad Reza Gholami ◽  
Asadollah Tavakoli ◽  
Mahdie Ahmadi ◽  
Jafar Rezaian ◽  
...  

Demyelination disorder is an unusual pathologic event, which occurs in the central nervous system (CNS). Multiple sclerosis (MS) is an inflammatory demyelinating disease that affects the CNS, and it is the leading cause of disability in young adults. Lysolecithin (LPC) is one of the best toxin-induced demyelination models. In this study, a suitable model is created, and the effect of fluoxetine treatment is examined on this model. In this case, it was assumed that daily fluoxetine treatment had increased the endogenous remyelination in the LPC model. This study was focused on investigating the influence of the fluoxetine dose of 5 or 10 mg/kg per day for 1 and 4 weeks on LPC-induced neurotoxicity in the corpus callosum region. It was performed as a demyelinating model in male Wistar rats. After 3 days, fluoxetine was injected intraperitoneally (5 or 10 mg/kg per day) for 1 and 4 weeks in each group. After completing the treatment course, the corpus callosum was removed to examine the gene expression and histological analysis was performed. The results of the histopathological study of hematoxylin and eosin staining of the corpus callosum showed that in 1 and 4-week treatment groups, fluoxetine has reduced the level of inflammation at the LPC injection site (5 and 10 mg/kg per day). Fluoxetine treatment in the luxol fast blue (LFB) staining of the corpus callosum has been led to an increase in myelination capacity in all doses and times. The results of the genetic study showed that the fluoxetine has significantly reduced the expression level of tumor necrosis factor-α, nuclear factor κβ, and induced nitric oxide synthase in comparison with the untreated LPC group. Also, the fluoxetine treatment has enhanced the expression level of the forkhead box P3 (FOXP3) gene in comparison with the untreated group. Fluoxetine has increased the expression level of myelination and neurotrophic genes such as myelin basic protein (MBP), oligodendrocyte transcription factor 2 (OLIG2), and brain-derived neurotrophic factor (BDNF). The outcomes demonstrated that fluoxetine reduces inflammation and strengthens the endogenous myelination in the LPC-induced demyelination model; however, supplementary studies are required for specifying the details of its mechanisms.

2021 ◽  
Vol 17 (2) ◽  
pp. 183-188
Author(s):  
Feda Makkiyah ◽  
Tiwuk S Susantiningsih, ◽  
Rahmah Hida Nurrizka ◽  
Wismaji Sadewo

Worldwide, cerebrovascular accidents (stroke) are the second leading cause of death and the third leading cause of disability. However, not many the histopathological study of progression in chronic stroke has been published so far. This study gives the detail explanation of mechanism of recovery and might give the idea of new timeline when to set up the treatment to regenerate restoration of damaged cells. Fourteen male Wistar rats (15–20 weeks, weighing 250-400 g) were used in this study. Prior to 7 days of adaptation to the laboratory environment, rats were divided into four groups. Sham group (n=2), rats that sacrificied 4th week (n=2), 8th week (n=5), 12th week(n=5). 90 minutes temporary MCAO procedures were performed using the Indonesian modified technique. CD31 and Doublecortin markers were used to evaluate angiogenesis and neurogenesis. The results showed that ventricle size of ipsilateral brain was not so affected as in week 12th compared to 8th week. Gliosis as a response to damage to the central nervous system was more dense in week 12th as oppose to week 4th. Regarding angiogenesis and neurogenesis, there is significant improvement of angiogenesis and neurogenesis within weeks, however 4th week post MCAO shows prominent recovery. We summarized that rat’s brain shows spontanenous improvement in chronic phase of stroke ischemia and angiogenesis and neurogenesis still happends until week 12th.


Author(s):  
Rasipin Rasipin ◽  
Edi Dharmana ◽  
Suharyo Hadisaputro ◽  
Suhartono .

ABSTRACTObjective: Goiter is an enlarged thyroid gland remained a health problem in the agricultural areas. Chlorpyrifos (CPF) is a pesticide widely used byfarmers. Previous studies proved that CPF exposure caused thyroid dysfunction. The objective of this study was to evaluate the effects of kefir on theinflammatory status and thyroid function in male Wistar rats after exposed to CPF using biochemical and histopathological assays.Methods: Male rats were divided into 4 groups, i.e., CPF 5+kefir (5 mg/kg+3.6 ml/200 g, respectively), CPF 5 (5 mg/kg), corn oil (CO 1 ml/200 g), andnegative control (NC: Without CPF, CO, and kefir).Results: Kefir supplementation dose 3.6 ml/200 g once a day for 28 days in the rats after exposed to CPF dose 5 mg/kg once a day for 14 days, inCPF 5+kefir as compared to CPF 5: Significantly (p<0.05) decreased serum tumor necrosis factor-α (TNF-α) level; significantly (p<0.01) maintainedserum levels of tumor growth factor-β (TGF-β) and thyroid stimulating hormone (TSH) not to decrease; not significant (p>0.05) decreased the level ofinterleukin-1β, cluster of differentiation-26 expression and level of T serum; not significant (p>0.05) maintained the level of anti-thyroid peroxidasenot to decrease; and not significant (p>0.05) increased the apoptosis index. This study suggests that CPF exposure causes the inflammatory processwhich leads to thyroid dysfunction.4Conclusion: Kefir supplementation significantly decreased the level of TNF-α and maintained the levels of TGF-β and TSH not to decrease, possible toreduce the inflammatory and thyroid dysfunction processes caused by exposure to CPF in experimental animals.Keywords: Kefir, Chlorpyrifos, Inflammation, Thyroid function. 


Author(s):  
Ebenezer Olatunde Farombi ◽  
Amos Olalekan Abolaji ◽  
Babatunde Oluwafemi Adetuyi ◽  
Olaide Awosanya ◽  
Mobolaji Fabusoro

Abstract Background Acrylonitrile (AN) is a neurotoxin that is widely used to manufacture synthetic fibres, plastics and beverage containers. Recently, we reported the ameliorative role of 6-gingerol-rich fraction from Zingiber officinale (Ginger, GRF) on the chlorpyrifos-induced toxicity in rats. Here, we investigated the protective role of GRF on AN-induced brain damage in male rats. Methods Male rats were orally treated with corn oil (2 mL/kg, control), AN (50 mg/kg, Group B), GRF (200 mg/kg, Group C), AN [50 mg/kg+GRF (100 mg/kg) Group D], AN [(50 mg/kg)+GRF (200 mg/kg) Group E] and AN [(50 mg/kg)+N-acetylcysteine (AC, 50 mg/kg) Group F] for 14 days. Then, we assessed the selected markers of oxidative damage, antioxidant status and inflammation in the brain of rats. Results The results indicated that GRF restored the AN-induced elevations of brain malondialdehyde (MDA), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and Nitric Oxide (NO) levels. GRF also prevented the AN-induced depletion of brain glutathione (GSH) level and the activities of Glutathione S-transferase (GST), glutathione peroxidase (GPx) and superoxide dismutase (SOD) in rats (p<0.05). Furthermore, GRF prevented the AN-induced cerebral cortex lesion and increased brain immunohistochemical expressions of Caspases-9 and -3. Conclusions Our data suggest that GRF may be a potential therapeutic agent in the treatment of AN-induced model of brain damage.


2016 ◽  
Vol 5 (3) ◽  
pp. 131-38
Author(s):  
Shabnam Movassaghi ◽  
Ali Yousefi Oudarji ◽  
Zahra Nadia Sharifi

Objective(s):  Methylenedioxymethamphetamine (MDMA) is a hallucinogenic drug of abuse which is the most popular drugs in the world and has been shown to induce apoptosis in kidney cells. As Pentoxifylline (PTX) increases cAMP and reduces tumor necrosis factor-α, the present study aimed to investigate the effects of pentoxifylline on kidney damage induced by acute administration of MDMA in male rat.Materials & methods: Thirty male rats (250-300 g) were randomly divided into five groups: including control (without any intervention), MDMA group ,the group received 7.5 mg/kg MDMA three times at every two hours for one day ,first experimental group, received 100 mg/kg PTX a week before MDMA administration, second experimental group received 100 mg/kg PTX Just in the time of the third injection of MDMA and the third experimental group received 100 mg/kg PTX followed by one dose of MDMA. Two weeks later, kidneys were removed and prepared for H&E staining, TUNEL and western blot techniques. Results: histopathological studies showed significantly decrease in the kidney cellular damage, in experimental group 1 compared to MDMA group. The number of TUNEL-positive cells was increased significantly in MDMA group. A significant difference was revealed in the mean number of TUNEL-positive cells between the rats treated with PTX before MDMA administration and MDMA group. Expression of active caspase-3 was significantly increased in the MDMA group. While the PTX treatment could significantly decrease when administrated before MDMA injections.Conclusion: Pentoxifylline can significantly reduce the severity of lesions in the kidney following administration of MDMA.


1981 ◽  
Vol 55 (4) ◽  
pp. 620-624 ◽  
Author(s):  
Kenneth G. Rieth ◽  
Giovanni Di Chiro ◽  
Laurence D. Cromwell ◽  
Paul E. McKeever ◽  
Paul L. Kornblith ◽  
...  

✓ Computerized tomography (CT) has made it easier to distinguish tumoral from nontumoral diseases of the central nervous system. In the presence of mass effect, however, this distinction may be difficult or impossible to make. Primary demyelinating disease may occasionally present as a focal cerebral mass. The authors report three cases of primary demyelinating disease of the brain involving the corpus callosum and periventricular white matter and associated with mass effect, which proved difficult to differentiate from infiltrating “butterfly” gliomas.


Author(s):  
Zafer Sahin ◽  
Alpaslan Ozkurkculer ◽  
Omer Faruk Kalkan ◽  
Ahmet Ozkaya ◽  
Aynur Koc ◽  
...  

Abstract. Alterations of essential elements in the brain are associated with the pathophysiology of many neuropsychiatric disorders. It is known that chronic/overwhelming stress may cause some anxiety and/or depression. We aimed to investigate the effects of two different chronic immobilization stress protocols on anxiety-related behaviors and brain minerals. Adult male Wistar rats were divided into 3 groups as follows ( n = 10/group): control, immobilization stress-1 (45 minutes daily for 7-day) and immobilization stress-2 (45 minutes twice a day for 7-day). Stress-related behaviors were evaluated by open field test and forced swimming test. In the immobilization stress-1 and immobilization stress-2 groups, percentage of time spent in the central area (6.38 ± 0.41% and 6.28 ± 1.03% respectively, p < 0.05) and rearing frequency (2.75 ± 0.41 and 3.85 ± 0.46, p < 0.01 and p < 0.05, respectively) were lower, latency to center area (49.11 ± 5.87 s and 44.92 ± 8.04 s, p < 0.01 and p < 0.01, respectively), were higher than the control group (8.65 ± 0.49%, 5.37 ± 0.44 and 15.3 ± 3.32 s, respectively). In the immobilization stress-1 group, zinc (12.65 ± 0.1 ppm, p < 0.001), magnesium (170.4 ± 1.7 ppm, p < 0.005) and phosphate (2.76 ± 0.1 ppm, p < 0.05) levels were lower than the control group (13.87 ± 0.16 ppm, 179.31 ± 1.87 ppm and 3.11 ± 0.06 ppm, respectively). In the immobilization stress-2 group, magnesium (171.56 ± 1.87 ppm, p < 0.05), phosphate (2.44 ± 0.07 ppm, p < 0.001) levels were lower, and manganese (373.68 ± 5.76 ppb, p < 0.001) and copper (2.79 ± 0.15 ppm, p < 0.05) levels were higher than the control group (179.31 ± 1.87 ppm, 3.11 ± 0.06 ppm, 327.25 ± 8.35 ppb and 2.45 ± 0.05 ppm, respectively). Our results indicated that 7-day chronic immobilization stress increased anxiety-related behaviors in both stress groups. Zinc, magnesium, phosphate, copper and manganese levels were affected in the brain.


Author(s):  
Semeleva E.V. ◽  
Blinova E.V. ◽  
Zaborovsky A.V. ◽  
Vasilkina O.V. ◽  
Shukurov A.S.

In this work, we studied the pharmacological activity of zinc and magnesium salts of 2-aminoethanesulfonic acid in white non-linear male rats with amyotrophic lateral sclerosis, which was modeled by neurotoxicantsimplication into the pelvic part of spinal cord. After the reproduction of the pathology in animals, the indices of motor activity were recorded in the Rotarod test, and morphological studies of spinal cord sections stained according to Nisl in the Belshovsky modification were carried out. It was shown that the magnesium salt of 2-aminoethanesulfonic acid (compound LHT-317) to a greater extent reduces the development of motor disorders in experimental animals compared with the control group on the 4th day of observation. The course of intravenous administration of the studied compounds of 2-aminoethanesulfonic acid did not inhibit morphological changes in the spinal cord that develop in degenerative-dystrophic pathology of the central nervous system: connections. Moreover, if, against the background of treatment with zinc salt, the total area of motor zones in animals of the experimental group exceeded that of control rats, then the number of motoneurons did not differ from the control.


Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 408
Author(s):  
Sherif R. Abdel-All ◽  
Zeinab T. Abdel Shakour ◽  
Dalia M. N. Abouhussein ◽  
Enji Reda ◽  
Thoraya F. Sallam ◽  
...  

The incorporation of cisplatin (CP) as a cytotoxic antineoplastic agent in most chemotherapeutic protocols is a challenge due to its toxic effect on testicular tissues. Natural compounds present a promising trend in research, so a new nutraceutical formulation (NCF) was designed to diminish CP spermatotoxicity. A combination of three nutraceutical materials, 250 mg Spirulina platensis powder (SP), 25 mg Tribulus terrestris L. extract (TT), and 100 mg fish oil (FO) were formulated in self-nanoemulsifying self-nanosuspension (SNESNS). SP was loaded into the optimized self-nanoemulsifying system (30% FO, 50% span 80/cremophor EL and 20% isopropanol) and mixed with TT aqueous solution to form SNESNS. For the SP, phytochemical profiling revealed the presence of valuable amounts of fatty acids (FAs), amino acids, flavonoids, polyphenols, vitamins, and minerals. Transmission electron microscopy (TEM) and particle size analysis confirmed the formation of nanoemulsion-based nanosuspension upon dilution. Method validation of the phytochemical constituents in NCF has been developed. Furthermore, NCF was biologically evaluated on male Wistar rats and revealed the improvement of spermatozoa, histopathological features, and biochemical markers over the CP and each ingredient group. Our findings suggest the potential of NCF with SNESNS as a delivery system against CP-induced testicular toxicity in male rats.


2021 ◽  
pp. 106689692199356
Author(s):  
Fleur Cordier ◽  
Lars Velthof ◽  
David Creytens ◽  
Jo Van Dorpe

Acute disseminated encephalomyelitis (ADEM) is a rare immune-mediated inflammatory and demyelinating disorder of the central nervous system. Its characteristic perivenular demyelination and inflammation aid in the differential diagnosis with other inflammatory demyelinating diseases. Here, we present a clinical case of ADEM, summarize its histological hallmarks, and discuss pitfalls concerning the most important neuropathological differential diagnoses.


1996 ◽  
Vol 54 (2) ◽  
pp. 331-334 ◽  
Author(s):  
L. A. V Peireira ◽  
M. A. Cruz-Höfling ◽  
M. S. J. Dertkigil ◽  
D. L. Graça

The integrity of myelin sheaths is maintained by oligodendrocytes and Schwann cells respectively in the central nervous system (CNS) and in the peripheral nervous system. The process of demyelination consisting of the withdrawal of myelin sheaths from their axons is a characteristic feature of multiple sclerosis, the most common human demyelinating disease. Many experimental models have been designed to study the biology of demyelination and remyelination (repair of the lost myelin) in the CNS, due to the difficulties in studying human material. In the ethidium bromide (an intercalating gliotoxic drug) model of demyelination, CNS remyelination may be carried out by surviving oligodendrocytes and/or by cells differentiated from the primitive cell lines or either by Schwann cells that invade the CNS. However, some factors such as the age of the experimental animals, intensity and time of exposure to the intercalating chemical and the topography of the lesions have marked influence on the repair of the tissue.


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