scholarly journals Effect of Coenzyme-Q10 on Doxorubicin-Induced Nephrotoxicity in Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Azza A. K. El-Sheikh ◽  
Mohamed A. Morsy ◽  
Marwa M. Mahmoud ◽  
Rehab A. Rifaai ◽  
Aly M. Abdelrahman

Nephrotoxicity is one of the limiting factors for using doxorubicin (Dox) as an anticancer chemotherapeutic. Here, we investigated possible protective effect of coenzyme-Q10 (CoQ10) on Dox-induced nephrotoxicity and the mechanisms involved. Two doses (10 and 100 mg/kg) of CoQ10 were administered orally to rats for 8 days, in the presence or absence of nephrotoxicity induced by a single intraperitoneal injection of Dox (15 mg/kg) at day 4 of the experiment. Our results showed that the low dose of CoQ10 succeeded in reversing Dox-induced nephrotoxicity to control levels (e.g., levels of blood urea nitrogen and serum creatinine, concentrations of renal reduced glutathione (GSH) and malondialdehyde, catalase activity and caspase 3 expression, and renal histopathology). Alternatively, the high dose of CoQ10 showed no superior nephroprotection over the low dose, as there were no significant improvements in renal histopathology, catalase activity, or caspase 3 expression compared to the Dox-treated group. Interestingly, the high dose of CoQ10 alone significantly decreased renal GSH level as well as catalase activity and caused a mild induction of caspase 3 expression compared to control, probably due to a prooxidant effect at this dose of CoQ10. We conclude that CoQ10 protects from Dox-induced nephrotoxicity with a precaution to dosage adjustment.

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Marwa M. M. Refaie ◽  
Entesar F. Amin ◽  
Nashwa F. El-Tahawy ◽  
Aly M. Abdelrahman

Nephrotoxicity is one of the limiting factors for using doxorubicin (DOX). Interleukin 1 has major role in DOX-induced nephrotoxicity, so we investigated the effect of interleukin 1 receptor antagonist diacerein (DIA) on DOX-induced nephrotoxicity. DIA (25 and 50 mg/kg/day) was administered orally to rats for 15 days, in the presence or absence of nephrotoxicity induced by a single intraperitoneal injection of DOX (15 mg/kg) at the 11th day. We measured levels of serum urea, creatinine, renal reduced glutathione (GSH), malondialdehyde (MDA), total nitrites (NOx), catalase, and superoxide dismutase (SOD). In addition, caspase-3, tumor necrosis factor alpha (TNFα), nuclear factor kappa B (NFκB) expressions, and renal histopathology were assessed. Our results showed that DOX-induced nephrotoxicity was ameliorated or reduced by both doses of DIA, but diacerein high dose (DHD) showed more improvement than diacerein low dose (DLD). This protective effect was manifested by significant improvement in all measured parameters compared to DOX treated group by using DHD. DLD showed significant improvement of creatinine, MDA, NOx, GSH, histopathology, and immunohistochemical parameters compared to DOX treated group.


2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Sheng-Min Hsu ◽  
Chang-Hao Yang ◽  
Fang-Hsiu Shen ◽  
Shun-Hua Chen ◽  
Chia-Jhen Lin ◽  
...  

Bortezomib is a proteasome inhibitor used for hematologic cancer treatment. Since it can suppress NF-κB activation, which is critical for the inflammatory process, bortezomib has been found to possess anti-inflammatory activity. In this study, we evaluated the effect of bortezomib on experimental autoimmune uveitis (EAU) in mice and investigated the potential mechanisms related to NF-κB inactivation. High-dose bortezomib (0.75 mg/kg), low-dose bortezomib (0.15 mg/kg), or phosphate buffered saline was given after EAU induction. We found that the EAU is ameliorated by high-dose bortezomib treatment when compared with low-dose bortezomib or PBS treatment. The DNA-binding activity of NF-κB was suppressed and expression of several key inflammatory mediators including TNF-α, IL-1α, IL-1β, IL-12, IL-17, and MCP-1 was lowered in the high-dose bortezomib-treated group. These results suggest that proteasome inhibition is a promising treatment strategy for autoimmune uveitis.


2021 ◽  
Author(s):  
Ömer Hazman ◽  
Hatice Evin ◽  
Mehmet Fatih Bozkurt ◽  
İbrahim Hakkı Ciğerci

Abstract Arbutine is one of the active substances used as a skin whitening agent in cosmetic products. Possible effects of arbutine on hepatocelluler carcinoma (HepG2) cells and cisplatin toxication in HepG2 cells were investigated in this study. Cytotoxicity, genotoxicity, oxidative stress, inflammation, apoptosis and proliferation levels were determined in experimental groups established for the purpose above. It was determined that when low dose of α-arbutine (in LD0 dose) was administered to HepG2 cells alone, it had no genotoxic and cytotoxic effects and no effects on inflammation, apoptosis and proliferation. However, when low dose of arbutine was used with cisplatin, it was observed that oxidative stress, inflammation, and genotoxicity levels increased as a result of cisplatin toxicity, but caspase 3 levels were not affected by this situation. As a result of high dose (in LD50 dose) of α-arbutine administration to HepG2 cells, it was determined that it would have anticarcinogenic effects by increasing oxidative stress, genotoxicity, inflammation and apoptosis and by suppressing proliferation. In the presented study it was determined that as well as α-arbutine had an anticarcinogenic effect on HepG2 cells in high doses, it might be protective to reduce the side effects caused by low dose (LD0 dose) of cisplatin treatment. In addition, it was concluded that α/β-arbutine-including cosmetic products were safe for cancer patients because α/β-arbutine had no effect on proliferation in HepG2 cells. In order to present the activity of arbutine isoforms more clearly it is recommended that studies should be conducted using healthy and different cell lines.


2019 ◽  
Vol 50 (6) ◽  
Author(s):  
Ali & et al.

 This study was aimed to displayed effect of this nanoparticles on pregnant mother and embryos. All females administration of AgNPs suspension orally during the gestational period (for 21day) in two doses low 2mg and high dose 20 mg /Kg body weight and the control group received D.W only. The pregnant females (60 females) include the control group and the treated group  was subdivided in to two groups, pre and post implantation and all the mothers weighted along the study. The embryos and their brains after retrieved weighted and the crow-rump length (CRL) measurement also. The results showed that the active form of Ag can be transport the placental barrier and blood brain barrier (BBB). This nanoparticles showed adverse effect and produced decreased in mothers weights in low dose 2mg/Kg/ B.Wt and higher dose 20mg/Kg/ B.Wt. Weights of embryos were lower clearly after exposure to AgNPs compare to control group. On the other hand, the weights of embryo's brain were decreased compare of control group in both doses. The CRL of embryos lowered after exposure to AgNPs in treatment groups when compare to control group.


Dose-Response ◽  
2021 ◽  
Vol 19 (4) ◽  
pp. 155932582110561
Author(s):  
Alexandra Jameus ◽  
Allison E. Kennedy ◽  
Christopher Thome

Cancer is the second leading cause of mortality worldwide accounting for almost 10 million deaths in 2020. Current standard of care treatment varies depending on the type and stage of disease, but commonly includes surgery, chemotherapy, and/or radiation therapy. There is evidence that whole- and half-body exposure to low dose ionizing radiation can also be an effective therapeutic due to its stimulation of anti-cancer immunity. One of the limiting factors for past clinical trials using low dose radiation therapy has been adverse hematological events. However, similar hematological changes are also frequently reported following standard of care treatments in oncology. This review summarizes the effects of various cancer therapies on hematologic toxicity through the evaluation of complete blood count reports. The reviewed literature elucidates hematological trends in patients undergoing chemotherapy, and both high and low dose radiation therapy. In general, high dose radiation and chemotherapy can result in widespread changes in blood counts, with the most severe effects related to leukopenia. Overall, compared to standard of care treatments, low dose radiation results in similar, yet more mild hematological changes. Taken together, hematological toxicities should not be a limiting factor in the applicability of low dose radiation as a cancer therapeutic.


2021 ◽  
Author(s):  
Ömer Hazman ◽  
Hatice Evin ◽  
Mehmet Fatih Bozkurt ◽  
İbrahim Hakkı Ciğerci

Abstract Arbutine is one of the active substances used as a skin whitening agent in cosmetic products. Possible effects of arbutine on hepatocelluler carcinoma (HepG2) cells and cisplatin toxication in HepG2 cells were investigated in this study. Cytotoxicity, genotoxicity, oxidative stress, inflammation, apoptosis and proliferation levels were determined in experimental groups established for the purpose above. It was determined that when low dose of α-arbutine (in LD0 dose) was administered to HepG2 cells alone, it had no genotoxic and cytotoxic effects and no effects on inflammation, apoptosis and proliferation. However, when low dose of arbutine was used with cisplatin, it was observed that oxidative stress, inflammation, and genotoxicity levels increased as a result of cisplatin toxicity, but caspase 3 levels were not affected by this situation. As a result of high dose (in LD50 dose) of α-arbutine administration to HepG2 cells, it was determined that it would have anticarcinogenic effects by increasing oxidative stress, genotoxicity, inflammation and apoptosis and by suppressing proliferation. In the presented study it was determined that as well as α-arbutine had an anticarcinogenic effect on HepG2 cells in high doses, it might be protective to reduce the side effects caused by low dose (LD0 dose) of cisplatin treatment. In addition, it was concluded that α/β-arbutine-including cosmetic products were safe for cancer patients because α/β-arbutine had no effect on proliferation in HepG2 cells. In order to present the activity of arbutine isoforms more clearly it is recommended that studies should be conducted using healthy and different cell lines.


2007 ◽  
Vol 21 (4) ◽  
pp. 439-443 ◽  
Author(s):  
Ching-Yin Ho ◽  
Ching-Ting Tan

Background The aim of this study was to compare the effect of antileukotriene (anti-LT), antihistamine, and a combination of anti-LT and antihistamine on the symptoms and nasal resistance in allergic rhinitis patients. Methods We performed a placebo-controlled study, with 120 persistent, moderate to severe allergic rhinitis patients randomly selected to receive the different treatments for 4 weeks: no treatment, 10 mg of cetirizine once per day, 20 mg of zafirlukast once per day, 20 mg of zafirlukast twice per day, a combination of 20 mg of zafirlukast and 10 mg of cetirizine once per day, or a combination of 20 mg of zafirlukast twice per day and 10 mg cetirizine once per day. The nasal secretion nitric oxide (NO) concentration, nasal symptom score, and nasal resistance were measured before and after treatment. Results Total symptom scores improved in each treated group compared with the control group (p < 0.05). Nasal obstruction significantly improved in the anti-LT-treated groups (p < 0.05). High-dose anti-LT or the combination of low-dose anti-LT and antihistamine significantly improved allergy symptoms compared with no treatment, low-dose anti-LT, or antihistamine alone (p < 0.05). Furthermore, anti-LT decreased NO concentration in nasal secretions (p < 0.05), regardless of the dose administered. Conclusion These results suggest that high-dose anti-LT alone or the combination of low-dose anti-LY and antihistamine can effectively treat allergic rhinitis.


1982 ◽  
Vol 63 (s8) ◽  
pp. 443s-445s ◽  
Author(s):  
◽  
Barry J. Materson

1. We randomized 475 men whose diastolic blood pressure was 92–109 mmHg to either placebo- or captopril-treated (37.5, 75 and 150 mg/day) groups for 7 weeks. 2. After 7 weeks, the placebo-treated patients were given hydrochlorothiazide (25 mg twice daily), as were two-thirds of each captopril-treated group, and they were observed for 7 additional weeks. 3. Captopril reduced blood pressure by 12.2 ± 0.8/9.4 ± 0.4 mmHg at 7 weeks (n = 323) and captopril plus placebo by 10.3 ± 1.9/10.2 ± 0.9 at 14 weeks (n = 83); placebo by 20 ± 1.7/3.4 ± 0.8 (n = 76); captopril plus hydrochlorothiazide by 24.4 ± 1.1/16.2 ± 0.6 (n = 173). The effect of low-dose captopril was similar to that of a high dose. The effect of twice-daily captopril appeared to be equal to that of thrice-daily treatment but monitoring studies are needed to confirm this. 4. Only 15 out of 384 (3.9%) of patients were dropped from the study because of adverse effects. 5. Low-dose captopril may be useful in patients with mild to moderate hypertension.


2008 ◽  
Vol 52 (No. 10) ◽  
pp. 437-444 ◽  
Author(s):  
S. Fleige ◽  
W. Preißnger ◽  
H.H.D. Meyer ◽  
M.W. Pfaffl

The study was conducted to elucidate the effects of orally administered lactulose in combination with <i>Enterococcus faecium</i> on immune response of the intestinal tract in pre-ruminant calves. The mRNA expression of pro- and anti-inflammatory cytokines and proliferation and apoptosis markers were investigated in jejunum, ileum, colon and caecum. Simmental calves were fed diets containing 1% (L1) or 3% (L3) lactulose and the probiotic strain of the genus <i>E. faecium</i>, and compared with a non treated control group. Primarily the high dose feeding with lactulose showed an effect on several mRNA gene expression parameters. In the jejunum a down-regulation of the anti-apoptotic marker Bcl-xl was determined and IL-10 mRNA gene expression was 2.6-fold up-regulated (<i>P</i> < 0.05). In the colon a 1.9-fold (<i>P</i> < 0.05) up-regulation of IL-10 and only in caecum an about 2-fold increase of TGF-β1 (<i>P</i> < 0.05) was found for both lactulose feedings. Caspase 3 was up-regulated in caecum only in the 3% lactulose treated group (<i>P</i> < 0.05). The enhanced apoptotic rate of caspase 3 seems to be associated with a decrease in crypth depth due to lactulose supplementation. The results indicated that mainly the high 3% lactulose dose in probiotic-fed calves has an affect on the intestinal immune function and on diverse apoptotic markers.


Author(s):  
M. K. Patel ◽  
D. J. Dave ◽  
R. C. Rathod ◽  
B. P. Joshi ◽  
D. J. Ghodasara

This work was conducted on six groups of day-old Cobb-400 broiler chicks to study the ameliorative effect of febuxostat on gout induced model. Clinical signs were noticed in birds of diclofenac control group II and low dose febuxostat treated group IV. During the study, 27.77% and 22.22% mortality were observed in diclofenac control group II and low dose febuxostat treated group IV, respectively. Febuxostat control group III and febuxostat (medium and high dose) treated groups V and VI had no mortality. Reduction in body weight gain and feed intake was observed in diclofenac control group II as compared to without treatment control group I at the end of every week during the experimental period of 21 days. Reduction in body weight gain and feed intake was observed in low dose febuxostat treated group IV as compared to control group at the end of 1st week. The average FCR was higher in diclofenac control group II (2.54) and low dose febuxostat treated group IV (2.14) as compared to control group (2.00). Kidney: body weight ratio was significantly high in diclofenac control group II as compared to control group at the end of experiment. Gross and microscopic lesions of visceral gout were mainly observed in chicks that died during the experiment from diclofenac control group II and low dose febuxostat treated group IV. The overall lesions showed that diclofenac was nephrotoxic and hepatotoxic in nature. Febuxostat at lower than the therapeutic dose did not prevent nephrotoxicity and hepatotoxicity caused by diclofenac leading to visceral gout. Febuxostat control III and febuxostat (medium and high dose) treated groups V and VI did not reveal any pathomorphological changes. Judicious use of febuxostat is safe in poultry birds between the limit of 4 mg/kg and 6 mg/kg


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