scholarly journals Protective effect of simvastatin in the cyclophosphamide-induced hemohrragic cystitis in rats

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.

2007 ◽  
Vol 72 (10) ◽  
pp. 1350-1364 ◽  
Author(s):  
Marie Stiborová ◽  
Helena Dračínská ◽  
Dagmar Aimová ◽  
Petr Hodek ◽  
Jiří Hudeček ◽  
...  

The antineoplastic agent ellipticine was investigated for its ability to induce the biotransformation enzyme NAD(P)H:quinone oxidoreductase (DT-diaphorase, EC 1.6.99.2) in male Wistar rats. Using the real-time polymerase chain reaction, the levels of NAD(P)H:quinone oxidoreductase mRNA were determined in livers, kidneys and lungs of rats treated intraperitoneally with ellipticine (40 mg/kg body weight) and of control (untreated) rats. Cytosolic fractions were isolated from the same tissues of control and ellipticine-treated rats and tested for NAD(P)H:quinone oxidoreductase protein expression and its enzymatic activity. The results demonstrate that ellipticine is a potent inducer of NAD(P)H:quinone oxidoreductase in rat livers and kidneys, while no induction of this enzyme was detectable in rat lungs. The increase in levels of NAD(P)H:quinone oxidoreductase mRNA correlates with the increase in expression of its protein and enzymatic activity, measured with menadione and 3-nitrobenzanthrone as substrates. The results, the identification of the potential of ellipticine to induce NAD(P)H:quinone oxidoreductase, suggest that this drug is capable of modulating biological efficiencies of the toxicants and/or drugs that are reductively metabolized by this enzyme.


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


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Supannikar Tawinwung ◽  
Dhirarin Junsaeng ◽  
Supanut Utthiya ◽  
Phisit Khemawoot

Abstract Background ECa 233 is a standardized extract of C. asiatica containing the triterpenoid glycosides, madecassoside to asiaticoside in the ratio of (1.5 ± 0.5):1. Anti-inflammatory activities of ECa 233 have been reported; however the immunomodulatory effects of ECa 233 on regulatory T cells, which have a pivotal role in immune regulation, has not been elucidated. Therefore, we investigated the effects of ECa 233 on regulatory T cells that may provide benefits in autoimmune and chronic inflammatory diseases. Methods ECa 233 was prepared as oral suspension in 0.5% carboxymethylcellulose and administered to male Wistar rats via oral gavage. The pharmacokinetics and toxicity of ECa 233 were evaluated. Splenic lymphocytes were isolated and analyzed by flow cytometry and qPCR to determine the immunomodulatory effects of ECa 233 on regulatory T cells. Results All rats had good tolerability to ECa 233 and other test preparations. The pharmacokinetic study showed low oral bioavailability for both triterpenoids, with the maximum plasma concentration reached at 4 h for asiaticoside and at 0.5 h for madecassoside. Multiple oral administration of ECa 233 reduced the frequency of T cells, particularly CD8 T cells in rats. ECa 233 enhanced the percentage of regulatory T cells, characterized by high expression of CD25+ and upregulation of FoxP3 gene. Conclusions The present study demonstrated that ECa 233 possesses immunosuppressive properties by enhancing regulatory T cells. These results provide in vivo evidence for the anti-inflammatory action of ECa 233, in line with previously reports, and the potential uses of ECa 233 in the treatment of chronic inflammatory and autoimmune diseases.


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.


2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Solomon Tsekohol Agu ◽  
Christian Okechukwu Ezihe ◽  
Paul Friday Itodo ◽  
Hyacinth Adakole Abu

Abstracts Background Chemotherapy is associated with male infertility. Cisplatin (CP), an antineoplastic agent has been successfully used for the treatment of diverse kinds of malignancies, however, the use of this effective agent could induce oxidative stress injury, nephrotoxicity, hepatotoxicity, and testicular damage. Combined CP chemotherapy with plant extracts can diminish the toxicity and enhance the antitumor efficacy of the drug. The objective of the study was to determine the protective effect Lophira lanceolata leaf extract (LLLE) on CP-induced toxicity on male reproductive organs. Methods The study was carried out with 30 (n = 30) male Wistar rats (Rattus norvegicus). The rats were randomly assigned into 6 groups of 5 rats each. Rats in group 1 (Control) were administered distilled water per os. Rats in group 2 were administered 5 mg/kg of CP intraperitoneally (i.p). Rats in groups 3 and 4 were administered per os LLLE at the doses of 200 and 400 mg/kg body weight and rats in groups 5 and 6 were administered 5 mg/kg body weight of CP + LLLE at the doses of 200 and 400 mg/kg body weight respectively. Results The results showed a significant decrease in the sperm parameters in the group treated with CP alone when compared with the control and there in the sperm parameters in the groups administered CP + LLLE. The body and organ weights of the rats were significantly (p < 0.05) decreased in the CP treated group relative to the control. However, there was an increase in the weight of the organs in the LLLE pretreated groups. The photomicrographs showed degenerative changes in the testicular tissues of the rats administered CP alone whereas the group pretreated with the LLLE showed amelioration induced by the CP. Our study revealed that CP treatment has deleterious effects on sperm parameters and testicular tissues and the accessory sex organs (Epididymis, prostate, seminal vesicles) of the rats. Oral administration of LLLE at 200 and 400 mg/kg bodyweight for 26 days conferred protective effects against testicular damage induced by CP. Conclusion This study revealed that pretreatment with LLLE protected against CP-induced testicular toxicity.


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. 


Molecules ◽  
2018 ◽  
Vol 24 (1) ◽  
pp. 36 ◽  
Author(s):  
Mónica Ríos-Silva ◽  
Rubén Santos-Álvarez ◽  
Xóchitl Trujillo ◽  
Rosa Cárdenas-María ◽  
Marisa López-Zamudio ◽  
...  

Capsaicin is an agonist of the transient receptor potential vanilloid type 1 (TRPV1) channel, which has been related to the pathophysiology of kidney disease secondary to diabetes. This study aimed to evaluate the chronic effect of capsaicin administration on biomarkers of kidney injury in an experimental rat model of diabetes. Male Wistar rats were assigned to four groups: (1) healthy controls without diabetes (CON), (2) healthy controls plus capsaicin at 1 mg/kg/day (CON + CAPS), (3) experimental diabetes without capsaicin (DM), and (4) experimental diabetes plus capsaicin at 1 mg/kg/day (DM + CAPS). For each group, 24-h urine samples were collected to determine diuresis, albumin, cystatin C, β2 microglobulin, epidermal growth factor (EGF), alpha (1)-acid glycoprotein, and neutrophil gelatinase-associated lipocalin (NAG-L). Blood samples were drawn to measure fasting glucose. After 8 weeks, the CON + CAPS and DM + CAPS groups showed increased diuresis compared to the CON and DM groups, but the difference was significant only in the DM + CAPS group. The two-way ANOVA only showed a statistically significant effect of CAPS on the urinary EGF levels, as well as a tendency to have a significant effect in the urinary NAG-L levels. The EGF levels decreased in both CAPS-treated groups, but the change was only significant in the CON + CAPS group vs. CON group; and the NAG-L levels were lower in both CAPS-treated groups. These results show that capsaicin had a diuretic effect in healthy and diabetic rats; additionally, it increased the urinary EGF levels and tended to decrease the urinary NAG-L levels.


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.


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