Protective Role of Quercetin in Carbon Tetrachloride Induced Toxicity in Rat Brain: Biochemical, Spectrophotometric Assays and Computational Approach

Carbon tetrachloride (CCL4) induces oxidative stress by free radical toxicities, inflammation, and neurotoxicity. Quercetin (Q), on the other hand, has a role as anti-inflammatory, antioxidant, antibacterial, and free radical-scavenging. This study explored protection given by quercetin against CCL4 induced neurotoxicity in rats at given concentrations. Male Wistar rats were divided into four groups Group C: control group; Group CCL4: given a single oral dose of 1 mL/kg bw CCL4; Group Q: given a single i.p injection of 100 mg/kg bw quercetin; and Group Q + CCL4: given a single i.p injection of 100 mg/kg bw quercetin before two hours of a single oral dose of 1 mL/kg bw CCL4. The results from brain-to-body weight ratio, morphology, lipid peroxidation, brain urea, ascorbic acid, reduced glutathione, sodium, and enzyme alterations (aspartate aminotransferase (AST), alanine aminotransferase (ALT), catalase, and superoxide dismutase) suggested alterations by CCL4 and a significant reversal of these parameters by quercetin. In silico analysis of quercetin with various proteins was conducted to understand the molecular mechanism of its protection. The results identified by BzScore4 D showed moderate binding between quercetin and the following receptors: glucocorticoids, estrogen beta, and androgens and weak binding between quercetin and the following proteins: estrogen alpha, Peroxisome proliferator-activated receptors (PPARγ), Herg k+ channel, Liver x, mineralocorticoid, progesterone, Thyroid α, and Thyroid β. Three-dimensional/four-dimensional visualization of binding modes of quercetin with glucocorticoids, estrogen beta, and androgen receptors was performed. Based on the results, a possible mechanism is hypothesized for quercetin protection against CCL4 toxicity in the rat brain.

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Free radical scavenging systems in developing rat brain

International Journal of Developmental Neuroscience ◽

10.1016/0736-5748(91)90010-j ◽

1991 ◽

Vol 9 (2) ◽

pp. 181-185 ◽

Cited By ~ 32

Author(s):

Bangalore R. Shivakumar ◽

Hindupur K. Anandatheerthavarada ◽

Vijayalakshmi Ravindranath

Keyword(s):

Free Radical ◽

Rat Brain ◽

Radical Scavenging ◽

Free Radical Scavenging ◽

Developing Rat

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Protective effect of apricot (Prunus armeniacaL.) on hepatic steatosis and damage induced by carbon tetrachloride in Wistar rats

British Journal Of Nutrition ◽

10.1017/s0007114509991322 ◽

2009 ◽

Vol 102 (12) ◽

pp. 1767-1775 ◽

Cited By ~ 35

Author(s):

Feral Ozturk ◽

Mehmet Gul ◽

Burhan Ates ◽

I. Cetin Ozturk ◽

Asli Cetin ◽

...

Keyword(s):

Oxidative Stress ◽

Carbon Tetrachloride ◽

Protective Effect ◽

Hepatic Steatosis ◽

Wistar Rats ◽

Liver Steatosis ◽

Radical Scavenging ◽

Hepatic Necrosis ◽

Control Group ◽

Cytoplasmic Matrix

The present study was planned to investigate the protective effect of 10 % and 20 % apricot-containing feed on carbon tetrachloride (CCl4)-induced hepatic steatosis and damage. Adult male Wistar rats (n42) were divided into six groups of seven each, as follows: control group; CCl4group; CCl4+10 % apricot group; CCl4+20 % apricot group; 10 % apricot group; 20 % apricot group. All apricot groups were fed with 10 % or 20 % apricot-containing feed for 5 months. CCl4injections were applied to the CCl4groups at the dose of 1 mg/kg for 3 d at the end of 5 months. In the CCl4group, vacuolated hepatocytes and hepatic necrosis were seen, especially in the centrilobular area. Hepatocytes showed an oedematous cytoplasmic matrix, large lipid globules and degenerated organelles. The area of liver injury was found significantly decreased with apricot feeding. Malondialdehyde and total glutathione levels and catalase, superoxide dismutase and glutathione peroxidase activities were significantly changed in the CCl4group and indicated increased oxidative stress. Apricot feeding decreased this oxidative stress and ameliorated histological damage. We concluded that apricot feeding had beneficial effects on CCl4-induced liver steatosis and damage probably due to its antioxidant nutrient (β-carotene and vitamin) contents and high radical-scavenging capacity. Dietary intake of apricot can reduce the risk of liver steatosis and damage caused by free radicals.

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Netupitant/palonosetron (NEPA) for prevention of delayed chemotherapy-induced nausea and vomiting (CINV) in multiple cycles of chemotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.29_suppl.211 ◽

2015 ◽

Vol 33 (29_suppl) ◽

pp. 211-211

Author(s):

Lee Steven Schwartzberg ◽

Richard J. Gralla ◽

Kimia Kashef ◽

Hope Rugo

Keyword(s):

Oral Dose ◽

Single Oral Dose ◽

Complete Response ◽

Control Group ◽

Double Blind ◽

Report Data ◽

Multiple Cycles ◽

To Receive ◽

Delayed Phase ◽

Significant Nausea

211 Background: Prevention of CINV in the delayed phase (24-120 h post-chemotherapy) and over multiple cycles of chemotherapy remains a challenge. NEPA, a fixed combination of the NK1 receptor antagonist (RA) netupitant (300 mg) and the 5-HT3 RA palonosetron (PALO; 0.5 mg), has demonstrated efficacy in multiple studies, in both acute and delayed phases, during the first cycle of moderately or highly emetogenic chemotherapy (MEC and HEC, respectively) regimens. Two clinical trials evaluated NEPA over multiple cycles of chemotherapy. We report data for the delayed phase for each cycle. Methods: Both studies were Phase 3, double-blind, active-controlled studies. In study 1 (MEC), patients were randomized 1:1 to receive a single oral dose of NEPA (n = 724) or PALO 0.5 mg (n = 725) on Day 1; following cycle 1, patients could participate in a multi-cycle extension phase. In study 2 (MEC or HEC), patients were randomized 3:1 to receive a single oral dose of NEPA on Day 1 (n = 309) or oral aprepitant (APR) 125 mg plus oral PALO 0.5 mg on Day 1, then APR 80 mg/d on days 2 and 3 of each cycle (n = 103). In both studies, all patients also received dexamethasone. Efficacy endpoints included complete response (CR; no emesis, no rescue medication) and no significant nausea. Results: In both studies, CR rates were consistently numerically higher with NEPA (Study 1 range: 77%-89%; Study 2 range: 83%-93%) than with PALO (Study 1; range: 69%-83%) or APR/PALO (Study 2; range: 78%-88%) in each cycle up to cycle 6 (Table). In both studies, rates of no significant nausea in the NEPA group were similar to or higher than in the control group. NEPA was well tolerated in both studies; treatment-related adverse events included constipation and headache. Conclusions: These studies demonstrate sustained efficacy of NEPA (administered as a single dose on Day 1) across multiple cycles of MEC or HEC for prevention of CINV in the delayed phase. Clinical trial information: 2009-016775-30; 2010-023297-39. [Table: see text]

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Free radical scavenging activity of Castanopsis indica in mediating hepatoprotective activity of carbon tetrachloride intoxicated rats

Asian Pacific Journal of Tropical Biomedicine ◽

10.1016/s2221-1691(12)60168-3 ◽

2012 ◽

Vol 2 (1) ◽

pp. S243-S251 ◽

Cited By ~ 16

Author(s):

Narayan Dolai ◽

Indrajit Karmakar ◽

RB Suresh Kumar ◽

Biswakanth Kar ◽

Asis Bala ◽

...

Keyword(s):

Free Radical ◽

Carbon Tetrachloride ◽

Radical Scavenging Activity ◽

Radical Scavenging ◽

Hepatoprotective Activity ◽

Free Radical Scavenging ◽

Free Radical Scavenging Activity ◽

Scavenging Activity ◽

Castanopsis Indica

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Antioxidant Potential of Morinda Lucida and Psidium Guajava Extracts and Actions Against Paracetamol- Induced Kidney and Liver Injuries in Rats

American International Journal of Biology and Life Sciences ◽

10.46545/aijbls.v2i1.57 ◽

2020 ◽

pp. 6-17

Keyword(s):

Free Radical ◽

Radical Scavenging ◽

Psidium Guajava ◽

Free Radical Scavenging ◽

Control Group ◽

Histopathological Analysis ◽

Dependent Manner ◽

Liver Injuries ◽

Antioxidant Agents

Antioxidant agents of plants origin have continued to attract interest because of the potential they hold in the maintenance of human health accompany with their minimal side effects. The present study sought to evaluate the comparative free radical scavenging activities of ethanol extracts of air dried Morinda lucida leaves (EMLL) and Psidium guajava leaves (EPGL) by measuring their ability to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, nitric oxide (NOˉ) radical, 2,2 azinobis-( 3-ethylbenzothiazoline-6-sulfonic acid) (ABTS*), and inhibit lipid peroxidation (LPO). Antioxidant activities of the extracts were also determined in the plasma of the rats fed with the extracts by assaying for antiradical activity against DPPH and NO radicals in vitro. In vivo antioxidant effects of the extracts were also evaluated in paracetamol treated rats. Twenty rats were randomly divided into four groups for this study. Group 1 received normal feed as control, group 2 received 14.30mg/kg b.w of paracetamol by gavage, groups 3 and 4 received 400mg/kg b.w of EMLL and EPGL each for 7 days plus paracetamol on the 8th day respectively. Catalase (CAT) and superoxide dismutase (SOD) activities and malondialdehyde (MDA) status were assayed for in the kidney, liver and serum. Histopathological examinations of liver and kidney were also carried out. The results showed that EMLL and EPGL exhibited free radical scavenging ability in dose dependent manner towards DPPH, NO, ABTS radicals as well as inhibition of LPO. The results of evaluation of the antioxidant potentials of the extracts while in the plasma showed that they were associated with free radical scavenging activity in vivo. Paracetamol treatment caused significant (p<0.05) decreases in SOD and CAT activities, and marked increase (p<0.05) in MDA levels when compared with the control. However, compared with paracetamol only group, the extracts caused significant (p<0.05) increase in SOD and CAT activities and decreased MDA levels. Histopathological analysis of kidney and liver showed that the extracts were able to offer protection against paracetamol-induced kidney and liver injuries. The extracts therefore have strong antioxidant and cytoprotection abilities.

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Preliminary Free Radical Scavenging, Brine Shrimp Lethality, Antimicrobial and Thrombolytic Activities of Aganosma dichotoma (Roth) K. Schum.

Bangladesh Pharmaceutical Journal ◽

10.3329/bpj.v17i2.22337 ◽

2015 ◽

Vol 17 (2) ◽

pp. 177-181

Author(s):

Sanjoy Chandra Dey ◽

Mohammd Firoz Khan ◽

Mohammad S Rahman ◽

Mohammad A Rashid

Keyword(s):

Free Radical ◽

Carbon Tetrachloride ◽

Brine Shrimp ◽

Soluble Fraction ◽

Radical Scavenging Activity ◽

Radical Scavenging ◽

Pharmaceutical Journal ◽

Free Radical Scavenging ◽

Clot Lysis ◽

Brine Shrimp Lethality

Bangladesh is a good repository of natural products. Numerous plants are available to facilitate the traditional treatments. Proper scientific evaluations are essential to explore the plant derived drugs. With this view, the crude methanol extract of leaves of Aganosma dichotoma (Roth) K. Schum. and its Kupchan fractions were screened for free radical scavenging, brine shrimp lethality, antimicrobial and thrombolytic activities. Among all extractives, the chloroform soluble fraction demonstrated the highest free radical scavenging activity with IC50 value 18.21 ?g/ml. Moreover, the chloroform soluble fraction showed significant brine shrimp lethality having LC50 value of 3.98 ?g/ml. On the other hand, the petroleum ether, carbon tetrachloride and chloroform soluble materials revealed mild to moderate antimicrobial activity with the zone of inhibition ranging from 7 to 14 mm. In the thrombolytic assay, the carbon tetrachloride soluble partitionate showed the highest clot lysis (30.48%). This is the first report of the comprehensive investigations of different extractives of A. dichotoma for the abovementioned bioassays. DOI: http://dx.doi.org/10.3329/bpj.v17i2.22337 Bangladesh Pharmaceutical Journal 17(2): 177-181, 2014

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Antimicrobial, Cytotoxic, Thrombolytic and Antioxidant Activities of Syzygium fruticosum (Roxb.) DC.

Bangladesh Pharmaceutical Journal ◽

10.3329/bpj.v17i1.22315 ◽

2015 ◽

Vol 17 (1) ◽

pp. 51-54

Author(s):

Somaia Haque Chadni ◽

Abdullah Al Hasan ◽

ATM Zafrul Azam

Keyword(s):

Free Radical ◽

Carbon Tetrachloride ◽

Soluble Fraction ◽

Radical Scavenging Activity ◽

Radical Scavenging ◽

Free Radical Scavenging ◽

Free Radical Scavenging Activity ◽

Scavenging Activity ◽

Zone Of Inhibition ◽

Aqueous Fraction

The crude methanol extracts of the bark and leaves of Syzygium fruticosum (Roxb.) DC. were partitioned with petroleum ether, carbon tetrachloride, chloroform and water for biological investigation. In the brine shrimp lethality bioassay, carbon tetrachloride soluble fraction of leaf extract (LCTF) showed significant lethality having the LC50 value 0.65 ?g/ml. In free radical scavenging activity screening (DPPH assay), chloroform fraction of methanolic extract of bark of S. fruticosum showed the highest free radical scavenging activity with IC50 value 20.01 ?g/ml. In the microbiological investigation, only chloroform soluble fraction of bark (BCF) and aqueous fraction of bark (BAF) showed mild antimicrobial activity with zone of inhibition ranging from 7 to 14 mm as compared to standard ciprofloxacin (zone of inhibition of 50 mm). In the study for thrombolytic property, different extracts of S. fruticosum revealed varying degrees of thrombolytic activity ranging from 33.46% to 62.51%. DOI: http://dx.doi.org/10.3329/bpj.v17i1.22315 Bangladesh Pharmaceutical Journal 17(1): 51-54, 2014

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Melatonin a Promising Candidate for DNA Double-Stranded Breaks Reduction in Patients Undergoing Abdomen-Pelvis Computed Tomography Examinations

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871521409666200324101701 ◽

2020 ◽

Vol 20 (7) ◽

pp. 859-864

Author(s):

Ali Eskandari ◽

Aziz Mahmoudzadeh ◽

Alireza Shirazi ◽

Farid Esmaely ◽

Carla Carnovale ◽

...

Keyword(s):

Computed Tomography ◽

Oral Dose ◽

Single Oral Dose ◽

Peripheral Blood ◽

Peripheral Blood Lymphocytes ◽

Control Group ◽

Controlled Clinical Trial ◽

Promising Candidate ◽

Blood Lymphocytes ◽

Ct Examination

Background and Objective: Cancer incidence is 24% higher in children and young adults exposed to Computed Tomography (CT) scans than those unexposed. Non-repairing of ionizing radiation-induced DNA Double-Strand Breaks (DSBs) can initiate carcinogenesis. In the present study, we aimed to investigate the radioprotective potential of melatonin against DSBs in peripheral blood lymphocytes of patients undergoing abdomen-pelvis CT examinations. Methods: This double-blind, placebo-controlled clinical trial was conducted on thirty patients. These patients were divided into two groups; group one (control) patients who have undergone the CT examination received a single oral dose of placebo, while in group two, patients received a single oral dose of 100mg melatonin. In both the groups, blood samples were collected 5-10min before and 30 minutes after the CT examination. The lymphocytes from these samples were isolated and DSBs were analyzed using γH2AX immunofluorescence microscopy. Results: Compared to the control group, the use of melatonin 1h before the CT examination caused a significant reduction in γH2AX-foci, indicating a reduction in DSBs. In addition, no side effect was observed in patients following 100mg melatonin administration. Conclusion: For the first time, this study has shown that melatonin has protective effects against radiationinduced genotoxicity in peripheral blood lymphocytes of patients undergoing abdomen-pelvis CT examinations. Therefore, melatonin can be considered as a promising candidate for reducing DSBs in patients undergoing abdomen-pelvis CT examinations.

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