scholarly journals Endogenous and exogenous serotonin, but not sumatriptan, ameliorate seizures and neuroinflammation in the pentylenetetrazole-induced seizure model in rats

Author(s):  
Ibrahim Ethem Torun ◽  
Yasemin Baranoglu Kılınc ◽  
Erkan Kilinc

ABSTRACT Background: Epilepsy has neuropsychiatric comorbidities such as depression, bipolar disorder, and anxiety. Drugs that target epilepsy may also be useful for its neuropsychiatric comorbidities. Objective: To investigate the effects of serotonergic modulation on pro-inflammatory cytokines and the seizures in pentylenetetrazole (PTZ)-induced seizure model in rats. Methods: Male Wistar rats were injected intraperitoneally with serotonin, selective serotonin reuptake inhibitor fluoxetine, 5-HT1B/D receptor agonist sumatriptan, or saline 30 min prior to PTZ treatment. Behavioral seizures were assessed by the Racine's scale. Concentrations of IL-1β, IL-6, and TNF-α in serum and brain tissue were determined by ELISA. Results: Serotonin and fluoxetine, but not sumatriptan, alleviated PTZ-induced seizures by prolonging onset times of myoclonic-jerk and generalized tonic-clonic seizures. The anti-seizure effect of fluoxetine was greater than that of serotonin. Likewise, serotonin and fluoxetine, but not sumatriptan, reduced PTZ-induced increases in the levels of IL-1β and IL-6 in both serum and brain tissue. None of the administered drugs including PTZ affected TNF-α concentrations. Conclusions: Our findings suggest that endogenous and exogenous serotonin exhibits anticonvulsant effects by suppressing the neuroinflammation. It seems that 5-HT1B/D receptors do not mediate anticonvulsant and anti-neuroinflammatory effects of serotonin.

Author(s):  
Neveen A. Salem ◽  
Amani M. Alsaedi ◽  
Bedor G. Alasmari ◽  
Razan Z. Almarghalani ◽  
Shahad M. Algobe ◽  
...  

Pregabalin (Lyrica) is an analog of the gamma-aminobutyric acid neurotransmitter,   approved for the treatment of epilepsy, generalized anxiety disorder, neuropathic pain, and fibromyalgia. The possibility for abuse and/or dependence on pregabalin has risen recently. Pregabalin is controlled in many countries including Saudi Arabia. However, unofficial use of this substance is also on the increase. The purpose of this study is to assess the potential neurotoxic effects associated with overdose prolonged pregabalin supplementation. Forty male Wistar rats were divided into Group (1) normal control received distilled water, Group (2) received pregabalin (150mg/kg), Group (3) received pregabalin (300 mg/kg), and Group (4) received pregabalin (600 mg/kg). pregabalin consumption in different doses resulted in significant dysregulation in neurotransmitter release, upsurge oxidative stress markers via enhancing lipid peroxidation and depleting antioxidant markers. Also, pregabalin doses evoked brain tissue inflammation through elevating TNF-α, IL-1β, and MCP-1, Moreover promoted brain tissue apoptosis by activating caspase -3 and suppressed Bcl2. Pregabalin effects on the aforementioned parameters were dose-dependent. These findings could highlight the potential neurotoxic effect of prolonged abuse of pregabalin supplementation through dysregulating brain neurochemical, inflammatory, oxidant/antioxidant, and apoptotic mediators.


Author(s):  
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Objective: The study evaluated the hypolipidemic and anti-inflammatory potential of the hydroalcoholic extract of P. Aculeata (HEPa/EtOAC) in Wistar rats fed with Westernized diet. Methods: The experiment was approved by the Ethics Committee (Federal University of Pernambuco-23076.027165 / 2010-21). The hydroalcoholic extract (HEPa/EtOAc) was obtained from the aerial parts of P. Aculeata and portioned by acetate/ethanol in different concentrations. 36 male Wistar rats were initially divided into two groups: Control (C, n = 6), fed a commercial diet (26g / 100g of protein; 63g / 100g of carbohydrates; 11g / 100g of lipids) and Westernized (W; n = 30) – fed an experimental diet (15g / 100g of protein; 51g / 100g of carbohydrates; 34 g/100g of lipids) receving water ad libitum. After 4 months of diet, W group was arbitrarily redistributed into six subgroups according to water supplementation, or different extracts concentrations: (n = 6 animals/group): W- distilled water (1mL/kg; po); WG – genfibrozil (140 mg/kg; p.o.); W35- 35 mg/kg; W70 – 70 mg /kg; p.o. and W140- 140 mg/kg; p.o for 30 days. The lipid profile and pro-inflammatory cytokines were analyzed. Results: The westernized diet caused dyslipidemia and the treatment with HEPa-EtOAc (140mg / kg), promoted a significant reduction in the concentration of pro-inflammatory cytokines, in total cholesterol, in the LDLc and serum triglycerides. Conclusion: The reduction of dyslipidemia and pro-inflammatory cytokines from the of P. Aculeata extract corroborate the ethnopharmacological potential of the plant, already used by the population for hypoglycemic purposes.


2020 ◽  
Vol 3 (1) ◽  
pp. 31-44
Author(s):  
Bermansyah ◽  
Gama Satria ◽  
Ahmad Umar

Introduction.Pulmonary contusions can cause a progressive inflammatory response. Activation of TNF-α cytokines and reactive oxygen species (ROS) can cause pulmonary cell death. Antioxidants can have the potential to neutralize ROS. The purpose of this study is to determine the effectiveness of antioxidant administration in maintaining pulmonary cell function in wistar rats that have been induced to experience pulmonary contusions through caspase-3 levels. Methods.This study was an in vivo experimental study conducted on thirty male wistar rats and divided into five groups (n = 6): control, pulmonary contusion + asthaxanthine 5 mg/kgBW, pulmonary contusion + vitamin C and E 50 mg/kgBW, pulmonary contusion + vitamin C and E 100 mg/kgBW, pulmonary contusion + vitamin C and E 200 mg/kgBW. The value of Caspase-3 is evaluated by the IHC. All data analyzes used SPSS 18. Results. Low doses of antioxidants have the potential to reduce pulmonary cell death in wistar rats induced by pulmonary contusions.Conclussion. Vitamin C and E effective to reduce polmonary cell death in pulmonary contusion.Keywords: antioxidants, vitamin C, vitamin E, pulmonary contusions animal model, apoptosis, caspase-3


Author(s):  
Masoumeh Gholami ◽  
Jamal Amri ◽  
Saeed Pazhoohan ◽  
Mehdi Sadegh

Abstract Objective Phytocannabinoids beyond the Δ9-tetrahy-drocannabinol have shown anticonvulsive effects. Also, alkylamides from Echinacea purpurea have been proved as cannabinomimetics. We examined the effect of the hydroalcoholic root extract of E. purpurea on pentylenetetrazol (PTZ)-induced tonic–clonic seizures and kindling model of epileptogenesis and the involvement of CB2 receptors as the mediator of this effect. Methods Male Wistar rats (200 ± 20 g) were used. Single intraperitoneal (i.p.) injection of PTZ (80 mg/kg) was used to induce tonic–clonic seizures. The kindling model of epileptogenesis was induced by daily injections of PTZ (37 mg/kg; i.p. for 15 days). Latency and duration of the stages were monitored for analysis. The hydroalcoholic root extract of E. purpurea was injected (i.p.) 20 min before seizure induction at the doses of 10, 50, 100 and 200 mg/kg. CB2 receptor antagonist SR144528 was injected (0.1 mg/kg; i.p.) 20 min before the Echinacea injection. Results In the tonic–clonic model, pretreatment with E. purpurea at the doses of 100 and 200 mg/kg significantly increased latencies to S2–S6, while it significantly decreased S6 duration and mortality rate. SR144528 injection before the injection of 100 mg/kg of E. purpurea significantly prevented the effects of the extract on S4–S6 latencies. In the kindling model, E. purpurea at the doses of 100 and 200 mg/kg significantly delayed epileptogenesis and decreased mortality rate, while SR144528 injection before the injection of 100 mg/kg of E. purpurea significantly blocked this effect of the extract. Conclusion These findings revealed the anticonvulsive and antiepileptogenesis effects of the E. purpurea root extract, which can be mediated by CB2 receptors.


2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Rasha A. Hassan ◽  
Walaa G. Hozayen ◽  
Haidy T. Abo Sree ◽  
Hessah M. Al-Muzafar ◽  
Kamal A. Amin ◽  
...  

This study is aimed at evaluating the preventive effect and at suggesting the mode of actions of naringin and hesperidin and their combination in diclofenac-induced hepatotoxicity. Male Wistar rats, intraperitoneally injected with diclofenac sodium (3 mg/kg b.wt/day), were orally treated with naringin (20 mg/kg b.wt/day) and hesperidin (20 mg/kg b.wt/day) and their combination for 4 weeks. The administrations of naringin and hesperidin to diclofenac-injected rats led to a significant decrease in the elevated serum ALT, AST, LDH, ALP, GGT, total bilirubin, TNF-α, and IL-17 levels as well as liver lipid peroxidation and liver p53 and caspase-3 mRNA expressions. In contrast, serum IL-4 level, liver GSH content, and liver GPx and SOD activities increased. In association, diclofenac-induced deleterious histological alterations including hydropic degeneration, cytoplasmic vacuolization, apoptosis, and focal hepatic necrosis of hepatocytes associated with inflammatory cells’ infiltration were remarkably improved by treatments with naringin and hesperidin. In conclusion, naringin, hesperidin, and their combination, which was the most potent, counteract diclofenac-induced liver injury via antioxidant, anti-inflammatory, and antiapoptotic actions. Thus, this study recommends the use of naringin and hesperidin or their combination to resolve the side effects of drugs like diclofenac on the liver.


Author(s):  
Efosa Godwin Ewere ◽  
Ngozi Paulinus Okolie ◽  
Oboso Edem Etim ◽  
Samson Adewale Oyebadejo

Aim: To investigate the effect of ethanol leaf extract of Irvingia gabonensis (ELEIG) on sodium arsenite (SA)-induced hepatic pro-inflammatory cytokines and haematological derangements in Wistar rats. Study Design: Fifty five Wistar rats weighing between 100 g and 161 g were randomly distributed to eleven (11) groups (n=5). Group 1 (control) had feed and water only. Group 2 received SA at a dose of 4.1 mg/kg body weight (kgbw) for 14 days. Groups 3-11 received ELEIG with or without SA. Place and Duration of Study: Biochemistry Department, University of Uyo and Biochemistry Department, University of Benin. The duration of the study was 14 days. Methodology: Treatment was done orally for 14 days. Immunological markers: tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-4 (IL-4), interleukin-10 (IL-10), and haematological indices: red blood cell (RBC) count, haemoglobin (HB) concentration, packed cell volume (PCV), mean cell haemoglobin (MCH), mean cell haemoglobin concentration (MCHC), mean corpuscular volume (MCV), white blood cell (WBC) count and its differentials and platelet (PLT) count were used to determine the immunomodulatory and haematological effects of the extract. Results: Intoxication with SA caused significant (p ˂ 0.05) increases in hepatic TNF-α, IL-1β, and IL-4 levels and a significant decrease in hepatic IL-10 level, relative to control. The SA treatment also caused significant (p ˂ 0.05) decreases in RBC, HB, PCV MCH, MCHC, MCV, PLT and monocyte counts as well as significant (p ˂ 0.05) increases in WBC, lymphocyte, basophil, eosinophil and neutrophil counts, relative to control. However, post-treatment and concomitant treatment with ELEIG ameliorated the noxious effect of SA. In addition, ELEIG alone at various doses produced results with most of the assayed parameters having values comparable with those control. Conclusion: These results indicate that ELEIG mitigates SA-induced inflammation and haematological perturbations in Wistar rats.


Author(s):  
Vineela Sathuluri ◽  
Thakur Santh Rani

Rutin is a flavonoid of the flavonol type found in many typical plants, such as buckwheat, passion flower, apple and tea. Acrylamide (ACR) is a known industrial toxic chemical that produces neurotoxicity characterized by progressive neuronal degeneration. Rats were randomly divided into Control, ACR, Pregabalin and Rutin treated groups. Male wistar rats were treated with ACR (50 mg/kg/ i.p.) for 4 weeks which produce typical symptoms of neuropathy in rats. Pregabalin (10 mg/kg) and Rutin (50 & 100 mg/kg) were administered orally for 4 weeks after one hour of ACR administration. ACR enhanced the production of reactive oxygen species (ROS). Treatment with Rutin significantly improved neurological score. Rutinsignificantly (p<0.001) attenuated acrylamide induced oxidative stress markers. The expression of Bcl-2 was up-regulated and TNF-α, IL-6 and Bax were down-regulated by rutin treatment. From our results, it can be concluded that rutinshowed an ameliorative effect against ACR induced neurotoxicity in rats through its antioxidant, anti-inflammatory and antiapoptotic actions.


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. 


2010 ◽  
Vol 25 (1) ◽  
pp. 43-46 ◽  
Author(s):  
Anna Carolina Batista Dantas ◽  
Francisco Fábio de Araújo Batista-Júnior ◽  
Larissa Freitas Macedo ◽  
Mariana Noronha Castro Mendes ◽  
Ítalo Medeiros Azevedo ◽  
...  

PURPOSE: Cyclophosphamide (CYP) is an antineoplastic agent used for the treatment of many neoplastic and inflammatory diseases. Hemorrhagic cystitis is a frequent side effect of CYP. Several studies show that simvastatin has important pleiotropic (anti-inflammatory and immunomodulatory) effects. The purpose of the study was to investigate the effect of simvastatin on bladder, ureter and kidney injury caused by CYP. METHODS: Adult male Wistar rats were randomly divided into three groups. The CYP/SIM group received simvastatin microemulsion by gavage during 7 days (10 mg/kg body wt) before the administration of CYP and the CYP/SAL group rats received saline 0.9%. The control rats were not treated. After that, all rats were treated with a single dose of CYP 200 mg/kg body wt intraperitoneally. The rats were killed 24 h after CYP administration. Plasma cytokines (TNF-α, IL-1β, IL-6) were measured by ELISA. Macro and light microscopic study was performed in the bladder, kidney and ureter. RESULTS: In the bladders of CYP/SIMV treated rats edema of lamina propria with epithelial and sub-epithelial hemorrhage were lower than in CYP/SAL treated rats. The scores for macroscopic and microscopic evaluation of bladder and ureter were significantly lower in CYP/SIMV rats than in CYP/SAL rats. The kidney was not affected. The expression of TNF-α, IL-1β and IL-6 was significatly lower in CF/SINV rats (164.8±22, 44.8±8 and 52.4±13) than in CF/SAL rats (378.5±66, 122.9±26 e 123.6±18), respectively. CONCLUSION: The results of the current study suggest that simvastatin pretreatment attenuated CYP-induced urotelium inflammation and decreased the activities of cytokines.


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