[Show abstract][Hide abstract] ABSTRACT: The present study was planned to investigate the role of sex hormone receptor gene expression in the pathogenesis of hepatocellular carcinoma (HCC). Adult male Wistar rats were divided into seven groups. Group (1) was negative control. Groups (2), (5), (6), and (7) were orally administered with N-nitrosodiethylamine for the induction of HCC, then group (2) was left untreated, group (5) was orally treated with curcumin, group (6) was orally treated with carvacrol, and group (7) was intraperitoneally injected with doxorubicin, whereas groups (3) and (4) were orally administered only curcumin and carvacrol, respectively. The HCC group showed significant upregulation in the androgen receptor (AR) and the estrogen receptor-alpha (ERα) gene expression levels in the liver tissue. On the contrary, HCC groups treated with either curcumin or carvacrol showed significant downregulation in AR and ERα gene expression levels in the liver tissue. In conclusion, the obtained data highlight that both AR and ERα but not estrogen receptor-beta (ERβ) gene expression may contribute to the male prevalence of HCC induced in male rats. Interestingly, both curcumin and carvacrol were found to have a promising potency in alleviating the male predominating HCC.
Full-text · Article · Jul 2015 · Asian Pacific journal of cancer prevention: APJCP
[Show abstract][Hide abstract] ABSTRACT: The present study aimed to investigate the efficacy of Rosmarinus officinalis total methanolic extract on colon
cancer- induced in rats. Rats were classified into 5 groups. Group (1) was control. Groups from (2) to (5) were
intrarectally injected with N-methylnitrosourea (MNU) for induction of colon cancer then group (2) was left
untreated (cancer group); group (3) was treated intraperitoneally with 5-fluorouracil while, groups (4 and 5) were
treated orally with 1400 and 2800 mg/kg b.wt. of R. officinalis extract respectively. Cancer group declared
significant increase in the expression levels of β-catenin and c-Myc genes in colon tissue. Furthermore, colon
cancer induced-rats demonstrated significant increase in colon COX-2, cyclin D1 and survivin expression in colon
tissue associated with significant elevation in the circulating levels of all studied biochemical markers. Additionally,
histopathological investigation of colon tissue sections in cancer group showed dysplasia and anaplasia in the
lining epithelial cells of the glandular structure. In the contrary, treatment of cancer group with 5-fluorouracil or R.
officinalis extract showed significant decrease in the expression levels of β-catenin and c-Myc genes. Also, all
treated groups exhibited marked decrease in COX-2, cyclin D1 and survivin expression in colon tissue accompanied
with a significant reduction in the circulating levels of the all studied biomarkers. As well as, marked improvement
in the histological structure of colon tissue was detected. In conclusion, the present study indicated that R.
officinalis extract possess promising therapeutic role against colon cancer through their antiinflammatory property,
antiproliferative capacity and apoptotic potential.
Key words: Colon cancer, N-methylnitrosourea, 5- fluorouracil, Rosemary, and Rats
Full-text · Article · Mar 2015 · Der Pharmacia Lettre
[Show abstract][Hide abstract] ABSTRACT: This study was designed to investigate the role of curcumin against hepatocellular carcinoma (HCC) induced in rats. Forty rats were divided into five groups. Group (1) was negative control. Groups (2), (4), and (5) were orally administrated N-nitrosodiethylamine for HCC induction, then group (2) was left untreated, and group (4) was treated orally with curcumin, while group (5) was intraperitoneally injected with doxorubicin. Group (3) was served as curcumin control group. Serum alpha-fetoprotein, alpha L-fucosidase and vascular endothelial growth factor levels were analyzed. Gamma glutamyl transferase (GGT) and heat shock protein gp96 (HSPgp96) gene expressions were detected by RT-PCR. The immunohistochemical analysis of proliferating cell nuclear antigen (PCNA) and Ki-67 expressions was performed. Apoptosis was detected using DNA fragmentation assay. Also, histological investigation of liver tissue was achieved. Untreated HCC group showed significant elevation in the studied biochemical markers and significant upregulation in GGT and HSPgp96 gene expression as well as marked increase in PCNA and Ki-67 expression. Furthermore, this group revealed no DNA fragmentation. Histological investigation of liver tissue sections in HCC group revealed a typical anaplasia. On the other hand, the curcumin-treated group showed a significant depletion in the studied tumor markers and a significant downregulation in GGT and HSPgp96 gene expression. Also, this group displayed remarkable decrease in PCNA and Ki-67 expression. Moreover, this group revealed an obvious DNA fragmentation. Interestingly, treatment with curcumin showed remarkable improvement in the histological features of liver tissue. This study revealed the promising therapeutic role of curcumin against hepatocellular carcinoma owing to its antiangiogenic, antiproliferative, and apoptotic effects.
[Show abstract][Hide abstract] ABSTRACT: Objective: This study aimed to investigate the efficacy of Boswellia serrata methylene chloride extract against colon cancer- induced in rats.
Materials and Methods Forty male rats were classified into 5 groups. Group (1) was control. Groups from (2) to (5) were intrarectally administered with N-methylnitrosourea for induction of colon cancer then group (2) was left untreated (cancer group); group (3) was treated intraperitoneally with 5-fluorouracil, while, groups (4 and 5) were treated orally with 1666.6 mg/kg and 3333.3 mg/kg of Boswellia serrata methylene chloride extract respectively. Serum MMP-7, MMP-9 and EGF, plasma TGF-β and TNF-α levels were assayed using ELISA procedure. Immunohistochemical technique was used for estimation of colon COX-2 and cyclin D1 expression. Colon β-catenin, K-ras and c- myc gene expression was detected by RT-PCR. Also, histological investigation of colon tissue was done.
Results: Colon cancer group showed significant elevation in the studied biochemical markers. In the contrary, the all treated groups showed significant reduction in these markers. Colon cancer group showed significant rise in COX-2 and cyclin D1 expression in colon tissue. In contrast, all treated groups exhibited marked deplation in COX-2 and cyclin D1 expression. Cancer group displayed significant up-regulation in the expression level of β-catenin K-ras and c-myc genes in colon tissue. While, all treated groups exhibted significant down-regulation in the expression levels of these genes. Histopathological investigation of colon tissue sections in cancer group showed dysplasia and anaplasis in the lining epithelial cells of the glandular structure. While, treatment with 5-fluorouracil or Boswellia serrata extract showed marked improvement in the histological feature of colon tissue.
Conclusion: The present study indicated that Boswellia serrata methylene chloride extract has a promising therapeutic role against colon cancer induced in rats through its potential antiinflammatory property, antiproliferative capacity and apoptotic activity.
Keywords: Colon cancer, Boswellia serrata, Inflammation, Proliferation, Apoptosis and Rats
Full-text · Article · Jan 2013 · International Journal of Pharmacy and Pharmaceutical Sciences
[Show abstract][Hide abstract] ABSTRACT: Objectives:
The present study assessed the potential role of leptin administration in the protection and intervention against glucocorticoid-induced secondary osteoporosis in female rats.
Materials and methods:
For this purpose five groups of female Sprague Dawley rats were classified into: (1) negative control group in which the healthy rats received saline as vehicle, (2) a group orally administered with prednisolone (5 mg kg b.wt.-1) daily for six months (osteoporotic group), (3) a group subcutaneously administered with leptin (400 microg kg b.wt.-1) three times weekly for six months (positive control), (4) a group orally administered with prednisolone daily with simultaneous subcutaneous administration of leptin three times weekly for six months (protective group), and (5) a group orally administered with prednisolone daily for six months then subcutaneously administered with leptin three times weekly for other six months (therapeutic group).
The obtained data revealed that prednisolone administration resulted in significant decrease in serum osteoprotegerin (OPG) level accompanied with significant increase in serum receptor activator of nuclear factor-κB ligand (RANKL) and beta2-microglobulin levels in comparison with the negative control group. Moreover, prednisolone significantly decreased bone mineral density and content of different areas of the right femur bones as compared to the negative control group. Furthermore, administration of leptin with/after stopping prednisolone administration resulted in a marked modulation in the majority of bone biomarkers as well as improvement in bone mineral density and content.
Leptin provided promising effect on bone through its direct action on bone and matrix mineralization.
No preview · Article · Oct 2012 · European review for medical and pharmacological sciences
[Show abstract][Hide abstract] ABSTRACT: This study was undertaken to investigate the anti-inflammatory role of fennel, carob, doum and mixture of them in improving the renal dysfunction induced in rats by the cyclosporine.
Sixty female albino rats were divided into six groups: healthy control rats, cyclosporine injected rats (positive control), other groups were injected by cyclosporine for 7 days and then diet was supplemented with either fennel, doum, carob or mixture of them. After 45 days of supplementation, rats were scarified. Serum and urinary samples were obtained for different biochemical analysis.
The analysis included the determination of creatinine levels in serum and urinary samples, serum ammonia, transforming growth factor-beta1 (TGF-beta1) and tumor necrosis factor-alpha (TNF-alpha), urinary N-acetyl-beta D-glucosaminidase (NAG), beta2 microglobulin as well as calculating the creatinine clearance. Also, an histopathological examination for the kidney tissue was performed.
The present study showed that cyclosporine induced the nephrotoxicity as appeared by elevation of serum and urinary levels of creatinine, urinary level of beta2 microglobulin, serum levels of ammonia, TGF-beta1 and TNF-alpha and the NAG level while decreased the creatinine clearance. Addition of fennel, carob, doum or mixture of them significantly improved the kidney functions. Moreover, anti-inflammatory status of animals injected with cyclosporine and supplemented with fennel, carob, doum and mixture of them, showed a significant amelioration in the kidney functions as compared to animals injected with the cyclosporine only. Histopathological investigation of kidney tissue of rat treated with the cyclosporine showed a moderate degree of renal damages. While, groups fed on fennel, carob, doum or mixture of them showed a great improvement in the kidney morphological structure.
Diet supplementation with fennel, carob, doum have a promising anti-inflammatory influence on attenuating the complications associated with the renal dysfunction.
Full-text · Article · Apr 2012 · European review for medical and pharmacological sciences
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Very little is known about the causes of AD, except that its end stages involve extensive neuronal loss and the appearance of distinctive neuropathological features. This study was under taken to investigate the role of α-chymotrypcin (α-ch) in management of AD-induced in ovariectomized rats. DESIGN: Sixty female Sprague Dawley rats were divided into four groups n=15, (1) normal control group (con), (2) group underwent surgery to remove ovaries (ovx control group), (3) ovx group received aluminum chloride in a dose of 17mg/kg daily for 2 months to induce AD (AD group), (4) AD group treated with α-chymotrypcin (α-ch) at dose (8.1unit/rat/day) which is equivalent to the recommended human dose (α-ch-treated group) for three months. At the end of the experimental period, rats were sacrificed; brain samples were obtained for different biochemical analyses and histopathological examination. The biochemical analyses included determination of tumor necrosis factor-α (TNF- α), IL-18, monocyte chemo attractant protein-1 MCP-1, FAS, B-cell lymphoma 2 (Bcl2). RESULTS: In comparison with normal control group, the ovx control group recorded significant increase in the brain levels of TNF-α, IL-18, MCP-1 and FAS. On the other hand, the brain level of Bcl2 was significantly decreased. Also, AD group showed a significant increase in TNF-α, IL-18, MCP-1 and FAS levels in brain tissue. In contrast, significant decrease in brain Bcl2 level was detected in AD group as compared to the ovx control group. However, the treatment of AD group with α-chymotrypcin caused an improvement in the most studied biochemical parameters as indicated by decreased brain levels of TNF-α, IL-18, MCP-1 and FAS accompanied with significant increase in the level of Bcl2 compared to AD group. Histopathological investigation of brain tissue of ovx rats administered with aluminum (AD group) showed AD plaques. While, AD group treated with α-chymotrypcin showed great improvement in the brain morphological structure with the disappearance of amyloid plaques. CONCLUSION: This study revealed that α-chymotrypcin significantly ameliorates the neuroinflammation characterizing Alzheimer's disease in ovariectomized rats due to it's proteolytic activity as well as it's anti-inflammatory effect.
No preview · Article · Mar 2012 · Experimental and toxicologic pathology: official journal of the Gesellschaft fur Toxikologische Pathologie
[Show abstract][Hide abstract] ABSTRACT: The current study was undertaken to investigate the protective role of melatonin (MEL) and acetyl-L-carnitine (ALC) against dexamethasone (DM)-induced neurotoxicity. Adult female rats (60) were divided into: (1) control group, (2) DM-treated group, (3) MEL-treated group, (4) ALC-treated group, (5) MEL- and DM-treated, and (6) ALC- and DM-treated group. Serum acetylcholinesterase (AchE) activity, malondialdehyde (MDA), nitric oxide (NO) level, catalase (CAT), superoxide dismutase (SOD) and glutathione-S-transferase (GST) activities were estimated. Gene expression of the prooxidants (NO synthases NOS-1, NOS-2 and heme oxygenases HO-1, HO-2) and antioxidant enzyme (GST-P1) as well as deoxyribonucleic acid (DNA) fragmentation analysis of brain tissue were investigated. Histological examination of the brain tissue was carried out. DM administration caused significant increase in serum AchE activity, MDA and NO levels accompanied with significant decrease in the antioxidant enzymes activity. Pretreatment with MEL or ALC prior DM has been found to reverse all the former parameters. On the genetic level, DM administration significantly increased the expression level of NOS-1, NOS-2, HO-1, and HO-2 messenger ribonucleic acids (mRNAs) and decreased that GST-P1-mRNA in brain tissue. Also, DM produced DNA fragmentation in brain tissue. Treatment with MEL or ALC prior DM administration tend to normalize the above mentioned parameters. These results were documented by the histological examination of brain tissue. The present study suggests that oxidative stress is involved in the pathogenesis of DM-induced neurotoxicity. The inhibition of oxidative stress via stimulation of the antioxidant enzymes by MEL and ALC pretreatment plays a central protective role in modulation of neurotoxicity induced by DM.
Full-text · Article · Mar 2012 · Journal of physiology and biochemistry
[Show abstract][Hide abstract] ABSTRACT: Alzheimer's disease (AD) is now the most common cause of dementia in the elderly. This study aimed to explore new markers for AD as total homocysteine (tHcy), insulin, insulin like growth factor-1 (IGF-1), interleukin-1β (IL-1 β) and tumor necrosis factor-α (TNF- α); to determine the modulatory effects of vitamin E (VE), acetyl-L-carnitine (ALC) and α-lipoic acid (LA) on the investigated parameters and to evaluate the possible mechanisms for the role of these nutraceutical in regression of AD that is induced in female rats. Our results revealed that brain acetylcholine esterase (AChE) activity and tHcy levels were significantly increased in AD model. Folic acid, vitamin B12 levels and Na+/K+ ATPase activity were markedly reduced. Plasma insulin and IGF-1 levels were noticeably decreased while plasma TNF- α and IL-1β concentrations were significantly increased, indicating that abnormal inflammatory response is associated with AD. Treatment by VE, ALC or LA restored the above mentioned parameters to nearly normal levels comparable to those achieved by donepezil. These findings indicate that tHcy, insulin, IGF-1, IL-1β and TNF-α may be considered as new biomarkers for AD. The present study sheds light on the potential restoring effects of VE, ALC and LA in AD model with special focus on the possible mechanisms. Our study provides evidence for the importance of dietary supplements in delaying the progression of age-related neurodegenerative diseases.
[Show abstract][Hide abstract] ABSTRACT: Cisplatin (CP), a broadly used anticancer drug, is widely known to induce acute renal failure as a result of renal tubular injury.
In this study, the effect of N-acetyl cysteine (NAC) or taurine (TAU) for protection against CP-induced nephrotoxicity was investigated.
A single dose of CP 1 mg/kg b.wt. for 4 days was given IP to the rats, 10 days rest, and then the dose was repeated for other 4 days. After CP administration, NAC or TAU was given IP in a dose of 50 mg/kg b.wt. 3 times weekly for 8 weeks.
CP-induced nephrotoxicity is reflected in high values of blood urea and creatinine levels. In addition, the significant increase in the β(2)-MG and N-acetyl-β-glucosaminidase enzymes exhibited a strong correlation with histology scores of overall proximal tubule damage as compared with the normal control values. Treatment with TAU or NAC after CP administration significantly ameliorated CP-induced nephritic oxidation stress markers as compared with CP-treated group. On the other hand, treatment with TAU or NAC after CP administration significantly ameliorated CP-induced nephritic inflammation with possible attenuation of renal injury.
These data suggest that oxidative stress and inflammation are involved in the pathogenesis of CP-induced acute renal failure. The inhibition in oxidative stress and the elevation of the total antioxidant capacity as well as the inhibition of the inflammatory biomarkers by NAC or TAU after CP administration may play a central role in modulation of nephrotoxicity induced by CP.
NAC and TAU have antioxidant and anti-inflammatory against CP-induced nephrotoxicity.
No preview · Article · Apr 2011 · Toxicology mechanisms and methods
[Show abstract][Hide abstract] ABSTRACT: The current study aimed to evaluate the potential role of dehydroepiandrosterone (DHEA) in the protection and intervention of glucocorticoid-induced secondary osteoporosis in female rats. For this purpose this study was conducted on five groups of female Sprague Dawley rats which were classified into: (1) negative control group received saline as vehicle, (2) osteoporotic group orally administered with prednisolone (5 mg/kg b.wt.) daily for six months, (3) positive control group orally administered with DHEA (250 mg/kg b.wt.) three times weekly for six months, (4) protective group orally administered with prednisolone daily with simultaneous oral administration of DHEA three times weekly for six months and (5) therapeutic group orally administered with prednisolone daily for six months then orally administered with DHEA three times weekly for other six months. The obtained data revealed that prednisolone administration resulted in significant decrease in serum osteocalcin (OC), 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2) D(3)) and osteoprotegerin (OPG) levels accompanied with significant increase in serum parathyroid hormone (PTH) and receptor activator nuclear factor kappa B ligand (RANKL) levels. Histopathological investigation of left femur bone showed that prednisolone administration produced compression of the reduced articular surface and atrophy of the epiphyseal bone. On the other hand, DHEA supplementation to osteoporotic rats increased serum OC, 1,25-(OH)(2) D(3) and OPG levels while decreased serum PTH and RANKL levels. Moreover, DHEA administration resulted in restoration of intact epiphyseal bony structure and articular surface. In conclusion, DHEA via its control on glucocorticoid activity and androgenic action provided potent effect on bone.
No preview · Article · Feb 2011 · Experimental and toxicologic pathology: official journal of the Gesellschaft fur Toxikologische Pathologie
[Show abstract][Hide abstract] ABSTRACT: The present study focused on evaluating the effect of different nutraceutical combinations 10 including primarose, omega 3 fatty acids, silymarin, coenzyme Q , antioxidants on tumor growth as well as the metabolic impact-induced by Ehrlich ascites carcinoma (EAC) inoculation in female mice. After 60 days of oral administration of the selected nutraceutical combinations, the tumor size was recorded. Also, serum and liver samples were obtained for different biochemical analyses. These analyses included the determination of serum arginase, L-fucosidase, lipid peroxidation, nitric oxide levels and total antioxidant capacity. Moreover, hepatic Na -K /ATPase activity, sodium and + + potassium content of hepatic tissue were also assayed. The present results revealed that EAC inoculation (0.2ml of EAC which contains 2.5×10 cells) causes significant increase in serum arginase, 6 L-fucosidase, , lipid peroxidation, nitric oxide levels and hepatic potassium concentrations, while, total antioxidant capacity, hepatic Na /K -ATPase activity and sodium concentrations were significantly + + decreased in EAC inoculated mice when compared to control one. On the other hand, the selected nutraceutical combinations significantly reduced tumor size and markedly improved most of the biochemical parameters associated with the inoculation of EAC. This study highlighted the potential effectiveness of the selected nutraceutical combinations in ameliorating the growth of implanted EAC as well as modulating the biochemical parameters that are involved during tumor development in mice.
Full-text · Article · Dec 2010 · Australian Journal of Basic and Applied Sciences