A Preliminary Clinical Study of Cyclophosphamide with Reduced Glutathione Asc Uroprotector

1989 ◽  
Vol 75 (3) ◽  
pp. 257-258 ◽  
Author(s):  
Maria Teresa Nobile ◽  
Maria Giuseppina Vidili ◽  
Marco Benasso ◽  
Marco Venturini ◽  
Michele Tedeschi ◽  
...  
Keyword(s):  
Clinical Study ◽  
Reduced Glutathione ◽  
Protective Role ◽  
Experimental Models ◽  
Microscopic Hematuria ◽  
Clinical Use ◽  
Thiol Compound ◽  
Preliminary Results

Reduced glutathione (GSH) has been reported to be an effective protector against cyclophosphamide-induced urotoxicity in experimental models, providing protection comparable to that of mesna. This paper describes our preliminary results of the clinical use of GSH in combination with cyclophosphamide. GSH was administered i.v. in two divided doses of 2.5 g, 15 min before and 30 min after escalating doses of cyclophosphamide ranging from 1.2 up to 1.6 g/m2 (1-h infusion). GSH was well tolerated and did not produce unexpected toxicity. The lack of bladder damage, including microscopic hematuria, supports the protective role of this thiol compound.

scholarly journals Sex differences in obesity-induced hypertension and vascular dysfunction: a protective role for estrogen in adipose tissue inflammation?

2016 ◽  
Vol 311 (4) ◽  
pp. R714-R720 ◽  
Author(s):  
Lia E. Taylor ◽  
Jennifer C. Sullivan
Keyword(s):  
Energy Homeostasis ◽  
Cell Activation ◽  
Immune Cell ◽  
Vascular Dysfunction ◽  
Protective Role ◽  
Experimental Models ◽  
Immune Cell Activation ◽  
The Subject ◽  
Associated Risk Factors

Obesity is a potent predictor of cardiovascular disease and associated risk factors, including hypertension. Systemic inflammation has been suggested by a number of studies to be an important link between excess adiposity and hypertension, yet the majority of the studies have been conducted exclusively in males. This is problematic since women represent ∼53% of hypertensive cases and are more likely than men to be obese. There is a growing body of literature supporting a central role for immune cell activation in numerous experimental models of hypertension, and both the sex of the subject and the sex of the T cell have been shown to impact blood pressure (BP) responses to hypertensive stimuli. Moreover, sex steroid hormones play an important role in energy homeostasis, as well as in the regulation of immune responses; estrogen, in particular, has a well-known impact on both cardiovascular and metabolic disorders. Therefore, the purpose of this review is to examine whether sex or sex hormones regulate the role of the immune system in the development of hypertension and related vascular dysfunction in response to metabolic changes and stimuli, including a high-fat diet.

scholarly journals Toxicity profile of anticancer drugs in acute lymphoblastic leukemia and protective role of vitamin E on these toxicities in albino rats

2015 ◽  
Vol 1 (1) ◽  
pp. 45
Author(s):  
Regina Roy ◽  
Hema CG ◽  
Geetha N
Keyword(s):  
Clinical Study ◽  
Vitamin E ◽  
Acute Lymphoblastic Leukemia ◽  
Animal Study ◽  
Lymphoblastic Leukemia ◽  
Haematological Toxicity ◽  
Protective Role ◽  
Albino Rats ◽  
Cytostatic Drug

<p class="abstract"><strong>Background:</strong> Objectives:<strong> </strong>(1) To study the spectrum of toxicity due to chemotherapy as per MCP841 protocol during the acute phase of treatment of patients with Acute Lymphoblastic Leukemia (ALL).<strong> </strong>(2) To study the same toxicities in albino rats and the protective role of vitamin E on these toxicities.<strong></strong></p><p class="abstract"><strong>Methods:</strong> This was a prospective clinical study for one year, in the department of medical oncology and paediatric oncology which was augmented by experimental animal study for 5 months using albino rats. For clinical study, patients diagnosed as ALL taking treatment as per MCP841 protocol were taken. Patients were followed up every day to detect the development of any type of adverse reactions or toxicity symptoms. Laboratory tests done during the course of chemotherapy were reviewed for any abnormality. Animal study involved 18 albino rats; rats were divided into 3 Groups; Group 1 - control (n=6), Group 2 - antileukaemic treated rats (n=6), Group 3 - antileukaemic drugs and vitamin-E treated rats (n=6). </p><p class="abstract"><strong>Results:</strong> In the clinical study major toxicities observed were haematological, metabolic, gastrointestinal, general infection, neurotoxicity, pancreatitis, pneumonitis and jaundice. Neurosensory toxicity presented as numbness in the extremities and hyperalgesia and myalgia. Histopathological examination of the internal organs of albino rats studied showed<strong> </strong>protection of vitamin E for the gastric toxicity, pancreatitis, cardiac toxicity, neuro toxicity and hepatic toxicity whereas there was no reduction in splenic and renal toxicities. In the case of haematological toxicity, protection was only minimal.</p><p class="abstract"><strong>Conclusions:</strong> The animal study revealed the protective role of vitamin E on cytostatic drug induced toxicities. </p><strong>Keywords: </strong>Acute lymphoblastic leukaemia (ALL), Antileukaemic drugs, Vitamin E (Vit. E), MCP841 protocol

scholarly journals Antioxidant and hepatoprotective property of squalene for counteracting the oxidative damage induced by methotrex- ate in experimental rats

2021 ◽  
Vol 64 (2) ◽  
pp. 199-206
Author(s):  
Edakkukaran Sudhakaran Sumi ◽  
Pavan Kumar Dara ◽  
Rosemol Jacob Mannuthy ◽  
Balaraman Ganesan ◽  
Rangasamy Anandan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reduced Glutathione ◽  
Histopathological Examination ◽  
Lipid Peroxide ◽  
Mucosal Injury ◽  
Protective Role ◽  
Bone Marrow Toxicity ◽  
Shark Liver Oil ◽  
Limited Application

Methotrexate (MTX), an antifolate drug, is extensively prescribed for patients suffering from diseases like cancer, psoriasis, neoplasms, and rheumatoid arthritis. Despite its effectiveness, MTX sometimes finds limited application because its undesirable side effects, including hepatic or renal impairment, bone marrow toxicity and gastrointestinal mucosal injury. Squalene, a highly unsaturated isoprenoid compound, isolated from shark liver oil has great potential in neutralizing the damaging effects triggered by free radicals. Therefore, in this study, the protective role of dietary squalene supplementation on oxidative stress induced by methotrexate in experimental rats was evaluated. A significant reduction was displayed in the activities of catalase (CAT) and superoxide dismutase (SOD) in MTX-intoxicated groups compared to other groups. Similarly, the activities of glutathione dependant enzymes (GPx and GST) and reduced glutathione (GSH) in MTX-induced groups were shown to be lower compared to the untreated control. Increased LPO (lipid peroxide) level was found in MTX-intoxicated groups compared to other groups. In addition, alterations in the levels of liver marker enzymes like AST, ALP, ALT, and LDH were noticed in MTX intoxicated groups compared to other groups. Biochemical results were confirmed by the histopathological examination of liver sections. In conclusion, the result obtained in the present study proposes that squalene exerts antioxidant activity and is capable of ameliorating oxidative stress and liver injury induced by MTX.

Loss of clusterin expression worsens renal ischemia-reperfusion injury

2010 ◽  
Vol 298 (3) ◽  
pp. F568-F578 ◽  
Author(s):  
Wenjun Zhou ◽  
Qiunong Guan ◽  
Chris C. H. Kwan ◽  
Huifang Chen ◽  
Martin E. Gleave ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Clinical Care ◽  
Kidney Injury ◽  
Protective Role ◽  
Experimental Models ◽  
Novel Therapy ◽  
Clusterin Expression

Prevention of ischemia-reperfusion injury (IRI) is a challenge in clinical care of the patients with kidney transplants or acute kidney injury, and understanding of the intrinsic mechanisms of resistance to injury in the kidney will lead to a novel therapy. Clusterin, a secreted glycoprotein, is an antiapoptotic protein in cancer cells. Our study is to investigate the role of clusterin in renal IRI. Renal IRI in mice was induced by clamping renal vein and artery for 45 or 50 min at 32°C. Apoptosis of renal tubular epithelial cells (TECs) was determined by FACS analysis. Clusterin expression was examined by Western blot or immunohistochemistry. Here, we showed that clusterin protein was induced in TECs following IRI, and more tubules expressed clusterin in the kidneys following ischemia at higher temperatures. In human proximal TEC HKC-8 cultures, clusterin was upregulated by removal of serum and growth factors in medium and was downregulated by TNF-α-IFN-γ mixture. The levels of clusterin were positively correlated with cell survival in these conditions. Knockdown or knockout of clusterin expression enhanced the sensitivity of TECs to apoptosis. In experimental models of renal IRI, deficiency in clusterin expression worsened the injury, as indicated by a significant increase in renal tissue damage with higher levels of serum creatinine and blood urea nitrogen and by a poorer recovery from the injury in clusterin-deficient mice compared with wild-type mice. Our data indicate that the reduction of inducible expression of clusterin results in an increase in TEC apoptosis in the cultures and renders mice susceptibility to IRI, implying a protective role of clusterin in kidney injury.

Possible prenatal impact of sertraline on human placental glutathione S-transferase-π

2011 ◽  
Vol 31 (5) ◽  
pp. 457-464 ◽  
Author(s):  
O Dalmizrak ◽  
G Kulaksiz-Erkmen ◽  
N Ozer
Keyword(s):  
Congenital Malformations ◽  
Inhibitory Concentration ◽  
Reduced Glutathione ◽  
Protective Role ◽  
Tricyclic Antidepressant ◽  
Glutathione S Transferase ◽  
Natural Ligand ◽  
The Brain

Sertraline (SER), a tricyclic antidepressant, is considered to belong to the group of selective amine reuptake inhibitors. Its ability to cross the blood–brain barrier and transplacental transport has been reported previously. It is widely distributed in the brain and is bound to human glutathione S-transferase-π (GST-π). If SER is taken during pregnancy, it gets accumulated in the embryo and fetus, and some studies have suggested it may cause congenital malformations, thus the study of the interaction of GST-π with antidepressants is crucial. In this study, the interaction of human placental GST-π with SER in the presence of the natural ligand, reduced glutathione (GSH) and a xenobiotic ligand, 1-chloro-2,4-dinitrobenzene (CDNB) was investigated. The Vmvalues obtained at variable [CDNB] and variable [GSH] were 61.3 ± 2.3 and 46.4 ± 1.7 U/mg protein, respectively. The kcatand kcat/ Kmvalues for GSH and CDNB were 3.63 × 106s−1, 2.59 × 1010M−1s−1and 4.79 × 106s−1, 1.29 × 1010M−1s−1, respectively. The half maximal inhibitory concentration value for SER was 4.60 mM. At constant [CDNB] and variable [GSH] the inhibition type was linear mixed-type, with Ks, α, and Kivalues of 0.14 ± 0.02, 2.90 ± 1.64, and 2.18 ± 0.80 mM, respectively. On the other hand, at fixed [GSH] and at variable [CDNB], the inhibition type was competitive, with Kivalue of 0.96 ± 0.10 mM. Thus, these findings weaken the importance of the protective role of GST against toxic electrophiles in vivo in adults, but due to its immature enterohepatic system SER may accumulate in the fetus and cause congenital malformations.

scholarly journals Oxidative Stress in the Muscles of the Fish Nile Tilapia Caused by Zinc Oxide Nanoparticles and Its Modulation by Vitamins C and E

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Aaser M. Abdelazim ◽  
Islam M. Saadeldin ◽  
Ayman Abdel-Aziz Swelum ◽  
Mohamed M. Afifi ◽  
Ali Alkaladi
Keyword(s):  
Oxidative Stress ◽  
Zinc Oxide ◽  
Zinc Oxide Nanoparticles ◽  
Nile Tilapia ◽  
Reduced Glutathione ◽  
Protective Role ◽  
Oxide Nanoparticles ◽  
Relative Quantification ◽  
Mrna Transcripts

The effects of zinc oxide nanoparticles (ZnONPs) on antioxidants in Nile tilapia muscles and the protective role of vitamins C and E were examined. Two hundred males of Nile tilapia were held in aquaria (10 fishes/aquarium). Fishes were divided into 5 groups: 40 fishes in each group; the first group was the control; the 2nd and 3rd groups were exposed to 1 and 2 mg/L of ZnONPs, respectively; and the 4th and 5th group were exposed to 1 and 2 mg/L of ZnONPs and treated with a (500 mg/kg diet) mixture of vitamin C and E mixture (250 mg/kg diet of each). Muscles were collected on the 7th and 15th day of treatments. Muscle malondialdehyde, reduced glutathione levels, superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GR), glutathione peroxidase (GPx), and glutathione-S-transferase (GST) activities were measured after treatments. Relative quantification of SOD, CAT, GR, GPx, and GST mRNA transcripts was detected in the muscles. Results showed that MDA and GSH concentration; SOD, CAT, GR, GPx, and GST activities; and mRNA expression were significantly decreased in groups exposed to ZnONPs. Vitamins C and E significantly ameliorated the toxic effects of ZnONPs. In conclusion, vitamins C and E have the ability to ameliorate ZnONP oxidative stress toxicity in Nile tilapia.

scholarly journals A study of the neuroprotective role of Punica granatum and rosuvastatin in scopolamine induced cognitive deficit in rats

2017 ◽  
Vol 6 (7) ◽  
pp. 1773
Author(s):  
Fariha Fatima ◽  
Dilshad A. Rizvi ◽  
Afroz Abidi ◽  
Ali Ahmad ◽  
Pooja Shukla ◽  
...  
Keyword(s):  
Standard Treatment ◽  
Neuroprotective Effect ◽  
Memory Function ◽  
Acetylcholinesterase Inhibitor ◽  
Punica Granatum ◽  
Protective Role ◽  
Experimental Models ◽  
Anticholinergic Agent ◽  
Model Of Alzheimer’S Disease

Background: The present work has been planned to find out the effect of Punica granatum and Rosuvastatin on learning and memory in Scopolamine induced cognitive deficits in rats. Scopolamine being an anticholinergic agent is used fervently in experimental models for memory deficits and has been widely implicated for the screening of cognitive dysfunction. Punica granatum (Pomegranate) has shown to suppress tumor neuronal cells, hence it can be a potential agent in providing neuroprotection for preventing the development and progression of AD. There are conflicting reports indicating the role of statins as a neuroprotective agent. This contradiction led us to investigate the effect of the role of Rosuvastatin on memory. The test agents were further compared to the standard treatment group acetylcholinesterase inhibitor i.e. Donepezil.Methods: Male wistar rats 150-200gms were divided into 4 groups of 6 rats each. Amnesia was induced by scopolamine 3mg/kg ip at day 5 in all the groups. Group1 (amnesic control) given distilled water; group 2(standard treatment i.e. Donepezil 0.5mg/kg orally); group 3(Rosuvastatin group10mg/kg orally); group 4 (Punica granatum juice 500mg/kg orally) The methods for validating cognition deficits were behavioural tests like Cook’s pole response and Passive Avoidance response.Results: It was evident from our research that the Punica granatum juice and Rosuvastatin effectively antagonized the scopolamine induced cognitive impairment in the paradigms studied. The neuroprotective effect of Punica granatum juice was better as compared to the Rosuvastatin group and the effects of the former were comparable with the standard treatment i.e. Donepezil group.Conclusions: Punica granatum has a remarkable protective role in memory function, learning, cognition and behavior in Scopolamine induced amnesia model of Alzheimer’s disease which was better than Rosuvastatin treatment.

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