Modulatory effects of l-carnitine on tamoxifen toxicity and oncolytic activity

2013 ◽  
Vol 33 (9) ◽  
pp. 968-979 ◽  
Author(s):  
AB Ibrahim ◽  
HH Mansour ◽  
SA Shouman ◽  
AA Eissa ◽  
SM Abu El Nour
Keyword(s):  
Antitumor Effect ◽  
Liver Enzymes ◽  
Combined Treatment ◽  
Lipid Peroxides ◽  
Ehrlich Ascites Carcinoma ◽  
Treated Group ◽  
Female Rats ◽  
Sod Activity ◽  
Beneficial Effects ◽  
Group I

The aim of this study was to investigate the protective effect of l-carnitine (l-CAR) in tamoxifen (TAM)-induced toxicity and antitumor activity. Adult female rats were randomly divided into four groups. Group I was served as control, groups II and III were treated with TAM (10 mg/kg, periorally) and l-CAR (300 mg/kg, intraperitoneally), respectively, while group IV was treated with both compounds. The treatment continued daily for 28 days. Administration of TAM resulted in significant increase in serum lipid profiles, liver enzymes, and bilirubin level. TAM produced a significant increase in lipid peroxides (LPO) level and nonsignificant change in nitrogen oxide (NO( x)) level accompanied with significant decrease in superoxide dismutase (SOD) activity of hepatic and uterus tissues and significant decrease in glutathione (GSH) content of uterus tissue. Administration of l-CAR for 1 h prior to TAM treatment decreased serum lipids and liver enzymes significantly and significantly increased SOD activity in liver and uterus tissues compared with TAM-treated group. Furthermore, it restored LPO and GSH levels and increased NO( x) level in uterus tissue. DNA fragmentation and the apoptotic marker, caspase-3, were not detected in the liver of all treated groups. Histopathologically, alterations in the liver and uterus structures after TAM treatment, which was attenuated after l-CAR administration. The antitumor effect and survival of the combined treatment of Ehrlich ascites carcinoma (EAC)-bearing mice was less than each one alone. l-CAR interestingly increased survival rate of EAC-bearing mice more than TAM-treated group. In conclusion, l-CAR has beneficial effects regarding TAM toxicity; however, it interferes with its antitumor effect.

Anticancer Effects of Tacrolimus on Induced Hepatocellular Carcinoma in Mice

2021 ◽  
Vol 14 ◽  
Author(s):  
Shireen Sami Mahmoud ◽  
Samia Hussein ◽  
Hayam Rashed ◽  
Eman M. A. Abdelghany ◽  
Alaa I. Ali
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cyclin D1 ◽  
Liver Enzymes ◽  
Combined Treatment ◽  
Treated Group ◽  
Nuclear Antigen ◽  
Enzyme Linked Immunosorbent Assay ◽  
Gamma Glutamyl Transferase ◽  
Anticancer Effects ◽  
Glutamyl Transferase

Background: Tacrolimus is a calcineurin inhibitor widely used for immunological disorders. However, there is a significant controversy regarding its effect on the liver. The present study was conducted to evaluate the anticancer effects of tacrolimus on an induced murine hepatocellular carcinoma (HCC) model and its possible hepatotoxicity at standard therapeutic doses. Methods: Fifty-four male mice were divided into five groups: a control healthy group, control HCC group, tacrolimus-treated group, doxorubicin (DOXO)-treated group, and combined tacrolimus- and DOXO-treated group. The activity of liver enzymes, including alkaline phosphatase, gamma-glutamyl transferase, lactate dehydrogenase, alanine transaminase, and aspartate transaminase, was determined. Serum vascular endothelial growth factor (VEGF) was measured using an enzyme-linked immunosorbent assay. A quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to measure the expression of proliferating cell nuclear antigen (PCNA), Bax, and p53 mRNA. Immunohistochemical staining for cyclin D1 and VEGF was performed. Results: Mice that received combined treatment with tacrolimus and DOXO exhibited the best improvement in all parameters when compared with the groups that received DOXO or tacrolimus alone (p < 0.001). Conclusion: The combination of DOXO and tacrolimus was more effective in the management of HCC compared with either agent alone. This improvement was detected by the reduction of liver enzymes and the improvement of the histopathological picture. The involved mechanisms included significant apoptosis induction demonstrated by upregulation of bax along with a reduction in angiogenesis demonstrated by downregulation of VEGF. This was accompanied by inhibition of cell cycle progression mediated by upregulated p53 and downregulated PCNA and cyclin D1.

scholarly journals Triazine Derivative as Putative Candidate for the Reduction of Hormone-Positive Breast Tumor: In Silico, Pharmacological, and Toxicological Approach

2021 ◽  
Vol 12 ◽  
Author(s):  
Muhammad Tayyab Imtiaz ◽  
Fareeha Anwar ◽  
Uzma Saleem ◽  
Bashir Ahmad ◽  
Sundas Hira ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Tumor ◽  
In Silico ◽  
Enzyme Level ◽  
Saline Group ◽  
Female Rats ◽  
Beneficial Effects ◽  
Group I

Background and objectives: Breast cancer is a heterogeneous disease that poses the highest incidence of morbidity among women and presents many treatment challenges. In search of novel breast cancer therapies, several triazine derivatives have been developed for their potential chemotherapeutic activity. This study aims to evaluate the N-nitroso-N-methyl urea (NMU)–induced anti–mammary gland tumor activity of 2,4,6 (O-nitrophenyl amino) 1,3,5-triazine (O-NPAT).Methods: The in silico modeling and in vitro cytotoxicity assay were performed to strengthen the research hypothesis. For in vivo experimentation, 30 female rats were divided into five groups. Group I (normal control) received normal saline. Group II (disease control) received NMU (50 mg/kg). Group III (standard control) was treated with tamoxifen (5 mg/kg). Groups IV and V received O-NPAT at a dose level of 30 and 60 mg/kg, respectively. For tumor induction, 3 intraperitoneal doses of NMU were given at a 3-week interval, whereas all treatment compounds were administered orally for 14 consecutive days. Biochemical and oxidative stress markers were estimated for all experimental animals. DNA strand breakage alongside inflammatory markers was also measured for the analysis of inflammation. The hormonal profile of progesterone and estrogen was also estimated.Results: The test compound presented a significant reduction in organ weight and restored the hepatic and renal enzymes. O-NPAT treatments enhanced the antioxidant enzyme level of catalase (CAT), superoxide dismutase (SOD), and total sulfhydryl (TSH), with a highly significant reduction in lactate dehydrogenase (LDH) and lipid peroxidation. Also, the decrease in fragmented DNA, hormonal levels (estradiol and progesterone), and inflammatory cytokines (IL-6 and TNF-α) justified the dosage efficacy further supported by histopathological findings.Conclusion: All results indicated the anti–breast tumor activity of O-NPAT and presented its possibility of exploitation for beneficial effects in breast cancer treatment.

scholarly journals EVALUATION OF PROTECTIVE POTENTIAL OF CITRUS AURANTIFOLIA (CHRISTM) SWINGLE PEEL EXTRACT IN ATTENUATING DOXORUBICIN-INDUCED HEPATOTOXICITY IN EXPERIMENTAL MODELS

2020 ◽  
Vol 10 ◽  
pp. 138
Author(s):  
Oladapo Elijah Oyinloye ◽  
Akinyinka Oyedolapo Alabi ◽  
David Damilola Oluwasusi ◽  
Abdullahi Akanji Murtala ◽  
Adeyinka Aderonke Aderinola ◽  
...  
Keyword(s):  
Liver Enzymes ◽  
Antioxidant Properties ◽  
Study Groups ◽  
Treated Group ◽  
Experimental Models ◽  
Female Rats ◽  
Distilled Water ◽  
Citrus Aurantifolia ◽  
Vacuolar Change ◽  
Peel Extract

Citrus aurantifolia is a very common, and widely cultivated and consumed for its antioxidant properties due to its robust flavonoids content. Doxorubicin (DOX) is an antibiotic broadly used in the treatment of different types of solid tumours, but its use also comes at a cost, organ toxicity. The curative and preventive properties of Citrus aurantifolia  peel extract (CAPE) in doxorubicininduced hepatotoxicity in Wistar rats were evaluated. Thirty female rats were divided into six groups of five (5) rats each in both curative and preventive studies. In curative study, five groups of rats (II – VI) received Doxorubicin (mixed with normal saline, 15 mg/kg body weight i.p) on day one, 24 hours after, graded doses of CAPE and alpha-lipoic acid (A.L.A.) were administered to groups II- V and VI respectively for 7 consecutive days. For the prophylactic study, groups II – V and VI received graded doses of CAPE and A.L.A. respectively, 24 hours after Doxorubicin was administered to groups II-VI. Groups treated with D.W. and A.L.A. were used as a negative and positive control, respectively Liver enzymes such as A.S.T., A.L.T. and A.L.P., including liver samples, were examined for histopathological changes. A significant reduction (p< 0.05) in serum A.S.T. and A.L.T. levels was observed in animals treated with CAPE 200 and 400mg/kg in the preventive study, while in curative, a significant reduction in an expected rise in serum A.S.T., A.L.T. and A.L.P. (p<0.05) was observed in animals treated with CAPE 400mg/kg when compared to the group treated with DOX + distilled water. Hepatocellular necrosis was observed in the histology of DOX- distilled water treated group. Besides, the hepatocytes of groups treated with CAPE (200 and 400mg/kg) in this study showed narrow foci of mild vacuolar change as compared with groups treated with the lowest dose of CAPE (100mg.kg) and distilled water, which revealed random foci of mild vacuolar change. This study has provided information that DOX damaged liver tissue due to an increase in liver enzymes and histopathological results showing tissue damaged in groups treated with lower doses of CAPE and distilled water.  This study further demonstrates that groups treated with CAPE 200, 400 mg/kg and A.L.A. protect hepatic damage induced by DOX.

scholarly journals The Essential Oil of Cymbopogon citratus Stapt and Carvacrol: An Approach of the Antitumor Effect on 7,12-Dimethylbenz-[α]-anthracene (DMBA)-Induced Breast Cancer in Female Rats

Molecules ◽  
2020 ◽  
Vol 25 (14) ◽  
pp. 3284
Author(s):  
Juan Pedro Rojas-Armas ◽  
Jorge Luis Arroyo-Acevedo ◽  
Miriam Palomino-Pacheco ◽  
Oscar Herrera-Calderón ◽  
José Manuel Ortiz-Sánchez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Essential Oil ◽  
Antitumor Effect ◽  
Tumor Volume ◽  
Physiological Saline ◽  
Saline Group ◽  
Female Rats ◽  
Cymbopogon Citratus ◽  
Breast Tumor Cell ◽  
Group I

C. citratus essential oil and carvacrol have shown an antitumor effect on breast tumor cell lines; the main objective of this research was to evaluate the antitumor effect of the essential oil of Cymbopogon citratus (EOCc) and carvacrol on 7,12-dimethylbenz [a] anthracene (DMBA)-induced breast cancer in female rats. Cancer was induced by a single administration of DMBA at dose of 80 mg/kg body weight (BW). A total of 54 female Holtzman rats were randomly assigned into 9 groups (n = 6). Group I: PS (Physiological saline); Group II: DMBA; Groups III, IV, and V: DMBA + EOCc at doses of 50, 100 and 200 mg/kg/day BW, respectively; Groups VI, VII, and VIII: DMBA + carvacrol at doses of 50, 100 and 200 mg/kg/day BW, respectively; and group IX: DMBA + EOCc + carvacrol at doses of 100 mg/kg/day BW. The treatment lasted 14 weeks. As results, EOCc showed a reduction in tumors as well as necrosis and mitosis. Animals treated with carvacrol did not show necrosis, mitosis, or infiltration. Carvacrol at dose of 100 mg/kg/day BW revealed a significant decrease in the cumulative tumor volume down to 0.11 ± 0.05 cm3 compared to 0.38 ± 0.04 cm3 of the DMBA group (p < 0.01). It is concluded that EOCc and carvacrol had an antitumor effect on DMBA-induced breast cancer in female rats.

scholarly journals Hepatotoxic and hematotoxic effects of sage oil-loaded ifosfamide nanoemulsion in Ehrlich ascites carcinomabearing mice

2021 ◽  
Vol 18 (6) ◽  
pp. 1205-1211
Author(s):  
Sahar M. AlMotwaa ◽  
Mayson H. Alkhatib ◽  
Huda M. Alkreathy
Keyword(s):  
Liver Enzymes ◽  
Reduced Glutathione ◽  
Ehrlich Ascites Carcinoma ◽  
Positive Control ◽  
Negative Control ◽  
Subsequent Treatment ◽  
Group I ◽  
Ehrlich Ascites ◽  
Wbc Count ◽  
Group 1

Purpose: To investigate the hepatotoxic and hematotoxic effects of sage oil-loaded ifosfamide (IFO) nanoemulsion (NE) in Ehrlich ascites carcinoma (EAC)-bearing mice. Methods: Ifosfamide (IFO) was loaded into a NE containing sage oil, and its hepatotoxic and hematotoxic effects were assessed in EAC-bearing mice. Female Swiss albino mice (n = 50) weighing 25 - 30 g (mean weight = 27.5 ± 2.50 g) were randomly assigned to five groups of ten mice each. With the exception of group 1, the mice were inoculated intraperitoneally (i.p.) with 2.5 × 106 EAC/mouse for 48 h. Group I served as negative control, C (-); group II served as positive control, C (+); while groups III - V were treated i.p. with 60 mg/kg IFO in 0.3mL water (free-IFO); 0.3 mL NE (SAGE-NANO), and 60 mg/kg IFO in 0.3 mL SAGE-NANO (SAGE-IFO), respectively. The treatments were administered for three days. Results: Treatment with 60 mg/kg bwt IFO (free-IFO) significantly elevated the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT, p < 0.05). However, subsequent treatment with SAGE-IFO significantly reduced the activity of these liver enzymes (p < 0.05). The concentration of reduced glutathione (GSH) as well as the activities of catalase and glutathione reductase (GR) significantly increased, while malondialdehyde (MDA) level decreased significantly in SAGE-IFO group, when compared with free-IFO group (p < 0.05). Treatment with SAGE-IFO significantly restored white blood cell (WBC) count and platelet levels which were altered by free-IFO (p < 0.05). Conclusion: The results obtained in this study suggest that loading IFO in sage oil-NE greatly reduces its hepatotoxicity and hematotoxicity.

scholarly journals Anti-Oxidant Effects of Silybum marianum Extracts on Diabetic Wistar Rats

2019 ◽  
Vol 5 (4) ◽  
pp. 145-150
Author(s):  
Uyovwiesevwa Ataihire Johnson ◽  
◽  
Eze Kingsley Nwangwa ◽  
John Chukwuka Igweh ◽  
◽  
...  
Keyword(s):  
Vitamin C ◽  
Antioxidant Enzyme ◽  
Enzyme Activities ◽  
Combined Treatment ◽  
Treated Group ◽  
Control Group ◽  
Antioxidant Enzyme Activities ◽  
Silybum Marianum ◽  
Group I ◽  
Anti Oxidant

Antioxidants are specialized macro-molecules that neutralize harmful substances; free radicals. These radicals supposedly harm tissues, destroy food items, and damage materials. In living organisms, antioxidants can take the form of enzymes, and may be regularly added to oils, metals, foodstuffs, as well as numerous other materials to mitigate the damaging effect of free radical. Current study was designed to investigate the biochemical changes in antioxidant enzyme activities, following administration of Silybum marianum (an ancient medicinal plant of the Carduus marianum family) on Alloxan-Induced, diabetic rats. One hundred and twenty-five (125) rats were procured, made to acclimatize for two weeks, and then randomly grouped into five (5) groups of (n=25). Group 1: Non-Diabetic (Control) rats, Group 2 diabetic untreated rats, while groups 3, 4 and 5 comprised of vitamin-C treated rats (diabetic), Silymarin (extract), and Vitamin C + Silymarin (extract) combined treatment respectively. After four weeks of treatment with test extract, animals were then sacrificed, and blood samples collected and assayed for biochemical [anti-oxidant] enzyme activity. Upon statistical analysis, one way Analysis of variance (ANOVA) showed Catalase (CAT), superoxide dismutase (SOD) and malonaldehyde (MDA) activities to have significantly decreased for extract + vitamin C treated group (Group V) when compared with control (Group I). It was also noted that the use of the combined antioxidants vitamin C and silymarin resulted in a significant reduction in ROS production with decreased SOD and CAT enzyme activities. It is therefore likely that, improvements in antioxidant enzyme activities are a function of extract and/or Vitamin C administration to animals. Thus, Silymarin has antioxidant and regenerative potentials to damaged tissues.

scholarly journals Anticancer activity of ylang-ylang essential oil in Ehrlich Ascites Carcinoma cell-treated mice

2020 ◽  
Vol 11 (4) ◽  
pp. 5752-5762
Author(s):  
Ajay P Malgi ◽  
Vijaykumar P Rasal ◽  
Vishal Shivalingappa Patil ◽  
Priyanka P Patil ◽  
Shamanad P Mallapur ◽  
...  
Keyword(s):  
Essential Oil ◽  
Complex Mixture ◽  
Ehrlich Ascites Carcinoma ◽  
Treated Group ◽  
Ehrlich Carcinoma ◽  
Control Group ◽  
Sod Activity ◽  
Standard Drug ◽  
Chemical Structures ◽  
Essential Components

Essential oils are secondary metabolites contains a complex mixture of with a diverse array of chemical structures, play a crucial role in the management of complex diseases like cancer via synergistic and antagonism effect. essential oil (YYEO) extracted from the flowers of Cananga is renowned forits fragrance, contained more than 150 essential components within it, and utilized in various diseases and cosmetics. Traditionally YYEO is being used as an aphrodisiac, , , antiseptic, in food and beverages as a fragrance agent. Due to the presence of a complex mixture of essential components in YYEO, we aimed the current study to assess the anticancer potential against Ehrlich Carcinoma (EAC) bearing mice. In antioxidant, growth, body weight, biochemical, , and serum estimation was evaluated with subsequent of the liver. 5- (5- FU) was used as a standard drug. YYEO showed potent antioxidant activity by DPPH assay. YYEO significantly reversed the , lymphocytes, WBC, and RBC numbers in the treated group compared with the disease control group. YYEO administration has restored the imbalanced levels of antioxidant such as MDA, GSH, and SOD activity. YYEO reversed the of the liver altered by the EAC in mice. In conclusion, a complex mixture of contained in YYEO could be the potent anticancer therapy in the future. Further studies are needed to identify the active principles and the mechanism involved in this activity.

scholarly journals Prophylactic Antioxidant Potential of Gallic Acid in Murine Model of Sepsis

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Harikesh Maurya ◽  
Vaishali Mangal ◽  
Sanjay Gandhi ◽  
Kathiresan Prabhu ◽  
Kathiresan Ponnudurai
Keyword(s):  
Lipid Peroxidation ◽  
Gallic Acid ◽  
Large Population ◽  
Cecal Ligation ◽  
Sepsis Group ◽  
Acid Pretreatment ◽  
Sod Activity ◽  
Group Iii ◽  
Beneficial Effects ◽  
Group I

Present study is to investigate the effect of Gallic acid pretreatment on survival of septic animals and oxidative stress in different organs like lungs, liver, kidney, spleen, and vascular dysfunction of mice. Sepsis was induced by cecal ligation and puncture (CLP) in healthy adult male albino mice (25–30 g) and was divided into 3 groups each consisting of 6 animals, that is, sham-operated (SO group (Group I), SO + sepsis (Group II), and Gallic acid + sepsis (Group III)). Group III animals were pretreated with Gallic acid at the dose rate of 20 mg/kg body weight for 2 days before induction of sepsis. Animals were sacrificed on 8th day and the tissue samples were obtained for further investigation on lipid peroxidation (LPO), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GSH). Gallic acid pretreatment significant (P<0.05) reduces kidney, spleen, liver, and lungs’ malondialdehyde level in septic mice. However, it fails to improve reduced glutathione level in all given organs, while, Gallic acid pretreated mice showed significant improvement in SOD activity of kidney and spleen when compared to septic mice. Finally, the beneficial effects of Gallic acid pretreatment in sepsis are evident from the observations that Gallic acid partially restored SOD and catalase activity and completely reversed lipid peroxidation. Further studies are required to find out the possible mechanisms underlying the beneficial effects of Gallic acid on large population.

scholarly journals Low intensity ultrasound effects over osteopenic female rats bones

2003 ◽  
Vol 11 (1) ◽  
pp. 17-24 ◽  
Author(s):  
Daniela Cristina Leite de Carvalho ◽  
Alberto Cliquet Jr
Keyword(s):  
Treated Group ◽  
The Body ◽  
Female Rats ◽  
Femoral Diaphysis ◽  
Pulsed Ultrasound ◽  
Beneficial Effects ◽  
Low Intensity Pulsed Ultrasound ◽  
Low Intensity ◽  
Significant Difference ◽  
Low Intensity Ultrasound

Several studies have already shown the beneficial effects of low intensity pulsed ultrasound on osteogenesis in fracture cases. However, few reports have related the ultrasound action in bone with some injury but without fracture. Thus, we induced a rat osteopenia model by ovariectomy and the proximal third of rat femur was stimulated by ultrasound (200mus burst of 1.5 MHz sine waves repeated at 1.0 kHz, 30mW/cm², SATA) for 20 min/day, during 20 days. After the treatment period, the body weight was significantly higher in the non-treated group than the treated one. No significant difference in bone mineral content was detected among the groups (p > 0.05). Also, no significant difference was noted in the mechanical properties of the femoral diaphysis. However, histologic investigations showed that the treated femur presented less microarchitectural deterioration than the non-treated group. Moreover, it was demonstrated that the treated group did show recent bone formation which was not there in the non-treated group. These results suggest that the low intensity ultrasound can interfere in a positive way on osteoporosis.

scholarly journals EFFECT OF OBESITY AND STATIN;

2017 ◽  
Vol 24 (02) ◽  
pp. 216-220
Author(s):  
Faizania Shabbir ◽  
M. Mazhar Hussain ◽  
Tausif Ahmed Rajput ◽  
Alamgir Khan
Keyword(s):  
High Fat Diet ◽  
Treated Group ◽  
Female Rats ◽  
Control Group ◽  
Chow Diet ◽  
Sprague Dawley ◽  
High Fat ◽  
Male And Female ◽  
Male And Female Rats ◽  
Group I

Objectives: To observe the effect of obesity and subsequent atorvastatinadministration on MPV in high fat diet induced obese male and female Sprague Dawley rats.Study Design: Randomized control trial (RCT). Setting: Department of Physiology, Army MedicalCollege, Rawalpindi. Animal procurement and blood sampling was done at National Instituteof Health (NIH), Islamabad and biochemical assays were performed at Centre for Research inExperimental and Applied Medicine (CREAM), Army Medical College, Rawalpindi. Period: Thestudy was completed in 12 months. Material and Methods: Ninety healthy Sprague Dawley(male and female) rats were purchased and divided randomly into three equal groups. Ratsin normal control group (Group I) were given normal chow diet for three weeks. Rats in obesecontrol group (Group II) were given high fat diet for three weeks. Rats in obese treated group(Group III) were administered atorvastatin for three weeks in a dose of 10 mg/kg/day orally bygavage method after obesity induction. Terminal sampling was done at the end of the studyby intra-cardiac puncture. MPV is a part of blood complete picture that was analysed by KX 21Sysmex Hematology Analyzer. Results: High fat diet induced obesity resulted in a significant(p < 0.05) increase in MPV. The MPV was significantly (p < 0.05) decreased after atorvastatinadministration. The result was comparable for both genders. Conclusions: Obesity increasesMPV and hence the risk of adverse cardiovascular outcome. Atorvastatin apart from its knownlipid lowering effect, decreases MPV and can play a beneficial role in decreasing cardiovascularmorbidity and mortality. 

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