scholarly journals Ficus septica Burm. F. Leaves Ethanolic Extract Induces Apoptosis in 7,12-Dimethylbenz[A]Nthracene-Induced Rat Liver Cancer Quatitavely

Author(s):  
Dita Brenna Septhea ◽  
Anindyajati Anindyajati ◽  
Andita Pra Darma ◽  
Ika Nurzijah ◽  
Agung Endro Nugroho ◽  
...  

The chemopreventive effect of Ficus septica Burm. f. leaves ethanolic extract (FLEE) was studied in 7,12-dimethylbenz[a]nthracene(DMBA)-induced rat liver cancer. Rats were divided into 5 group, 5 rats (5 wk of age Sprague Dawley rat) in each group. Group 1 was control diet group, administered with 0,5% CMC-Na as vehicle. FLEE was administered 750 mg/kgBW and 1500 mg/kgBW starting 4 wk until 5 wk after DMBA administration at the first until fifth wk to group 2 and group 3. Group 4 was control extract group, administered  with 750 mg/kgBW and group 5 was DMBA group. DMBA is a carcinogen to induce liver cancer was also administered in DMBA control group and all animals were necropsied at 6 wk after DMBA administration. Activity of inducing apoptosis was detected using Double Staining method in 750 mg/kgBW FLEE group compared to control group but no in 1500 mg/kgBW FLEE group resulted in 100% dead. Apoptotic cells would have orange flourescence but normal cells would have green flourescence detected by flourescence microscope. To investigate the protein that involved in apoptotic mechanism, we studied p53 expression using Imunohistochemistry (IHC). There was no difference expression of p53 in both tested and control groups. Based on the results, FLEE has a potency as chemoprentive agent because its activity on inducing apoptosis in liver cancer with p53-independent pathway. The mechanism of apoptosis induction of this extract needs to be explored by observing the expression of related proteins.Keywords: apoptosis, Ficus septica, liver cancer, p53 independent pathway

2007 ◽  
Vol 98 (5) ◽  
pp. 937-943 ◽  
Author(s):  
Claudia Di Giacomo ◽  
Rosaria Acquaviva ◽  
Andrea Piva ◽  
Valeria Sorrenti ◽  
Luca Vanella ◽  
...  

The aim of the present study was to verify whether the oral administration of cyanidin 3-O-β-d-glucoside (C3G) might counteract damage induced by chronic exposure (28 d) to ochratoxin A (OTA) in rats and if its effect may be mediated by haeme oxygenase-1 (HO-1). Forty male Sprague–Dawley rats, individually caged, were divided into four groups of ten animals. A control group received a commercial diet, group C3G received the control diet supplemented with C3G (1 g/kg feed), group OTA received the control diet supplemented with 200 parts per billion of OTA, and group OTA+C3G received the OTA group diet supplemented with C3G (1 g/kg feed). After 4 weeks of treatment animals were killed and the liver, kidneys and brain of each rat were collected and homogenised to evaluate non-proteic thiol groups (RSH), lipid hydroperoxide (LOOH) levels, HO-1 expression and DNA fragmentation. Rats of the OTA group showed a significant (P < 0·001) decrease in RSH content of kidney and liver and a significant (P < 0·001) increase of LOOH in all the examined tissues compared with the control group. In the OTA+C3G group both RSH content and LOOH levels were similar to those observed in the control group, demonstrating that C3G was able to counteract the effects of OTA. A significant (P < 0·001) induction of HO-1 was evident in kidney and liver of both OTA and C3G groups. DNA damage occurred in all the examined tissues of the OTA group, whereas C3G was able to prevent it. The present study confirmed that the effects of OTA are mediated by oxidative stress and demonstrated that C3G efficiently counteracted deleterious effects of OTA because of its antioxidant and HO-1-inducing properties.


Author(s):  
G. F. Mukhammadieva ◽  
A. B. Bakirov ◽  
D. O. Karimov ◽  
Ya. V. Valova ◽  
M. M. Ziatdinova ◽  
...  

The aim of the study was to study the effect of hepatoprotective drugs on the expression of the Sod1 gene in rats with ethanol liver damage.Materials and methods. Male outbred white rats were used in the experiment. Five groups of animals were formed, 14 individuals each. Distilled water was administered to rats of the 1st group (control); Group 2 — ethanol at a dose of 5 g/kg of body weight; Group 3 — ethanol and heptor at a dose of 72 mg/kg; Group 4 — ethanol and mexidol at a dose of 50 mg/kg; Group 5 — ethanol and OMU at a dose of 50 mg/kg. The drugs were administered 1 hour before the introduction of ethanol. 24 and 72 hours after the introduction of ethanol (7 individuals), the animals were decapitated and the liver was removed. The expression level of the Sod1 gene was assessed using real-time reverse transcription PCR.Results. The fold change in Sod1 expression in rat liver after 24 h practically did not change in response to the introduction of ethanol to the animals. A tendency to a slight decrease was observed in relation to changes in the expression of Sod1 with the use of heptor and mexidol, while under the influence of OMU, the expression level increased moderately. After 72 h, the exposure to ethanol was accompanied by a slight decrease in the frequency of expression of the Sod1 gene. A similar trend was observed with respect to changes in Sod1 expression with the use of heptor, mexidol, and OMU.Conclusion. The results obtained indicate that the introduction of both ethanol and the prophylactic use of hepatoprotective drugs did not lead to significant changes in the level of Sod1 gene expression in rat liver. Additional studies are needed to identify the mechanisms of regulation of the antioxidant system, as well as the search for drugs that affect the transcriptional activity of genes.


2017 ◽  
Vol 474 (7) ◽  
pp. 1195-1203 ◽  
Author(s):  
Yasemin Sunucu Karafakıoğlu ◽  
Mehmet Fatih Bozkurt ◽  
Ömer Hazman ◽  
A. Fatih Fıdan

The aim of the present study was to investigate the effects of safranal on cisplatin-induced nephrotoxicity and oxidative stress in rats. Adult male Sprague–Dawley rats were randomly divided into five groups. The control group received physiological saline; animals in Group 2 received only safranal and in Group 3 received only cisplatin; 5 days of safranal treatment was performed following administration of cisplatin for the animals in Group 4; 5 days of safranal pretreatment was applied to the animals in Group 5 before administration of cisplatin. Cisplatin (7 mg/kg) was intraperitoneally injected as a single dose and safranal (200 mg/kg) was administered by gavage. Biochemical and histopathological methods were utilized for evaluation of the nephrotoxicity. The concentrations of creatinine and urea in plasma and levels of malondialdehyde (MDA) and glutathione (GSH) as well as total antioxidant status (TAS) and total oxidant status (TOS) were determined in kidney tissue. Administration of cisplatin to rats induced a marked renal failure, characterized with a significant increase in plasma creatinine and urea concentrations. MDA and TOS levels of rats that received cisplatin alone were not significantly different compared with those of the control group, but GSH and TAS levels in the only cisplatin-administered group were significantly decreased. Safranal administration produced amelioration in biochemical indices of nephrotoxicity in both plasma and kidney tissues when compared with the only cisplatin-administered group, pretreatment with safranal being more effective. As a result, safranal treatment might have a protective effect against cisplatin-induced nephrotoxicity and oxidative stress in rat.


Author(s):  
Mohammed Abdulrazzaq Assi1

Aim The current study was designed to estimate the influence of Nigella sativa and Eurycoma longifolia pre-treatment and Lead acetate administration on the reproductive hormonal and spermiogram of rats. Materials and Methods: Five groups of Sprague Dawley rats have been divided into 6 rats each. Distilled water was given to Group 1 (NC) and set as the negative control. Lead acetate 20 mg/kg/day orally for one month was administered to Group 2 (PC) and set as the positive control. Group 3 (T1) were administered 20 mg/kg LA and 300 mg/kg Nigella sativa both orally/day for one month. Group 4 (T2) were received 20 mg/kg LA and 500 mg/kg Eurycoma longifolia orally/day for one month. Group 5 (T3) were administered 300 mg/kg Nigella sativa, 20 mg/kg LA, and 500 mg/kg Eurycoma longifolia orally/day for one month. Results: In this study, five groups of Sprague Dawley rats have been divided into 6 male rats each and grouped as follows; Group 1(Negative control); Group 2 (Positive control; 20mg/kg lead acetate); Group 3 (LA 20mg/kg + NS 300mg/kg); Group 4 (LA 20mg/kg + EL 500mg/kg); Group 5 (LA 20mg/kg+ NS 300mg/kg + EL 500mg/kg). All administrations were given daily for 30 days. The rats were euthanized and serum and epididymal samples were collected for reproductive hormonal assays and spermiogram determination. The estrogen concentration was less (p less than 0.05) in the EL treated group, whereas in the positive control (PC), the concentration of follicle stimulation hormones, as well as luteinizing hormones, were lower (p less than 0.05). Testosterone concentration was found to be higher (p less than 0.05) in the PC in comparison to other groups. The motility, concentration, and viability of the sperm were all low in the PC and high (p less than 0.05) in the treatment groups. The sperm abnormality was higher in the PC in compared with other groups. Conclusion: In conclusion, this study showed the preventive effect of Nigella sativa and Eurycoma longifolia administration against alterations in spermiogram and hormones caused by LA.


Author(s):  
Irfan Aziz ◽  
Birendra Shrivastava ◽  
Chandana Venkateswara Rao2 ◽  
Sadath Ali

Liver disease or liver cancer is the sixth most common cancer and the third leading cause of cancer mortality in the world. Hepatitis viral infection, food additives, alcohol, fungal toxins (aflatoxins), toxic industrial chemicals, air and water pollutants are the major risk factors of liver cancer. Moreover, due to high tolerance of liver, HCC is seldom detected at an early stage and once detected treatment faces a poor prognosis in most cases.Fumaria indica possesses hepatoprotective activity as evidenced by the significant and dose dependent restoring the activities of entire liver cancer marker enzymes, diminution in tumor incidence, decrease in lipid peroxidation (LPO) and increase in the level of antioxidant enzymes (GSH, CAT, SOD, GPx and GST) through scavenging of free radicals, or by enhancing the activity of antioxidant, which then detoxify free radicals. These factors protect cells from ROS damage in NDEA and CCl4-induced hepatocarcinogenesis. Histopathological observations of liver tissues too correlated with the biochemical observations. Thus, present investigation suggested that the Fumaria indica would exert a chemoprotective effect by reversing the oxidant-antioxidant imbalance during hepatocarcinogenesis induced by NDEA and CCl4. Besides Fumaria indicais very much effective in preventing NDEA-induced multistage hepatocarcinogenesis possibly through antioxidant and antigenotoxic nature, which was confirmed by various liver injury and biochemical tumour markers enzymes. The hepatoprotective activity of a Fumaria indicaof 50 % ethanolic extract was studied using rats. The animals received a single intraperitoneal injection of N-nitrosodiethylamine 200mg/kg body wt followed by subcutaneous injection of CCl4 in a dose of 3 ml/kg body wt. Fumaria indica extract dose dependently and significantly the increase in serum hepatic enzyme levels after NDEAand CCl4 treatment compared to the toxin control group. The results of this study confirmed the antioxidant and hepatoprotective activity of the Fumaria indicaextract against carbon tetrachlorideand N-nitrosodiethylamine induced hepatotoxicity in rats. In addition to this, studies on molecular aspect of hepatoprotective therapy will give mechanistic information in hepatoprotective therapy and also critical balance should be there between the animal model and clinical research. The hepatoprotective properties of Fumaria indicashould provide useful information in the possible application in hepatic liver disease.


Author(s):  
Mustafa Salah Hasan ◽  
Ayman Barzan Abdulgafor ◽  
Maher Saber Owain ◽  
Mohammed Ali Hussein ◽  
Qusay Mohammed Aboud ◽  
...  

This study aimed to evaluate the liver, kidney damage caused by S. typhimurium and to estimate the oxidative damage in association with this bacteria. A highly virulent isolates of S. typhimurium were obtained from the department of internal and preventive medicine/ College of Veterinary Medicine/ University of Baghdad. A twenty five local rabbits of both genders with age range (2-4 months) weeks old were used for this study, the rabbits were divided randomly into five groups each group contains 5 rabbits :- group 1: drenched orally with 5 ml of normal saline and consider as control group, group 2: were drenched orally with (5 ml) suspension which contain (5��109 CFU) of Salmonella typhimurium and regarded as infected group, group 3 were drenched orally with (5 ml) suspension which have (5��109 CFU) of Salmonella typhimurium then treated with a single dose of gentamicin alone at 0.05ml/kg (5mg/ml) orally after presence of signs (after 24hrs. post inoculation), group 4 were drenched (5 ml) suspension having (5��109 CFU) of Salmonella typhimurium then treated with a single dose of Ca-EDTA alone at 40mg/kg orally after presence of signs (after 24hrs. post inoculation) and group 5 were drenched (5 ml) suspension that contain (5��109 CFU) of Salmonella typhimurium then treated with a single dose of combined gentamicin at 0.05ml/kg (5mg/ml) orally after presence of signs (after 24hrs. post inoculation) and Ca-EDTA 40mg/kg after presence of signs (after 24hrs. post inoculation).The results of biochemical profile showed a significant increase (p less than 0.05) in ALT, creatinine and urea levels in infected group as compared with control group, while, the treated groups especially group 5 showed a significant improvement in ALT, Urea and creatinine levels which returned to relative normal levels as compared with infected group after 96hrs. post treatment. Also, the results of oxidative stress showed a significant increase in the levels of MDA in G2, G3, G4 and G5 after 48 hrs. post treatment, while the level of GSH showed a significant decrease in the level at 48hrs., both were returned to relative normal levels after 96hrs.post treatment especially in group 5.In conclusion, S. typhimurium can causing liver and kidney damage which is manifested by increase ALT, Urea and Creatinine. Also, MDA and GSH is increased due to salmonellosis.


2010 ◽  
Vol 30 (7) ◽  
pp. 603-615 ◽  
Author(s):  
Mikiya Fujieda ◽  
Taku Morita ◽  
Keishi Naruse ◽  
Yoshihiro Hayashi ◽  
Masayuki Ishihara ◽  
...  

We investigated whether pravastatin ameliorates renal damage induced by cisplatin (CP). Forty-three male Wistar rats were divided into four groups: rats treated with a control diet for 19 days and saline injection on day 14 (group1), group 1 with pravastatin treatment with 19 days (group 2), group 1 with CP injection on day 14 (group 3), and group 2 with CP injection (group 4). Renal function and serum lipids, renal malondialdehyde (MDA) and glutathione (GSH) levels, glutathione peroxidase (GPx) mRNA expression and activity, and kidney triglyceride (TG) concentrations were measured. Histology was evaluated by light microscopy with immunohistochemistry for p53, p53-upregulated modulation of apoptosis (PUMA), and terminal deoxynucleotide transferase dUTP nick end-labeling (TUNEL) staining. CP induced renal tubular damage with a higher MDA level, increased PUMA expression, p53- and TUNEL-positive cells counts, elevation of serum lipids, and decreased GSH level, GPx mRNA expression, and activity. Pravastatin partially ameliorated CP-induced renal injury, based on suppression of the renal MDA and TG levels, decreased p53 expression, and apoptosis in CP-treated rats. These findings suggest that pravastatin has a partial protective effect against CP nephrotoxicity via antioxidant activity as well as attenuation of the p53 response, and lipid-lowering effects.


2016 ◽  
Vol 43 (5) ◽  
pp. 348-353 ◽  
Author(s):  
IGOR NAGAI YAMAKI ◽  
RUY VICTOR SIMÕES PONTES ◽  
FELIPE LOBATO DA SILVA COSTA ◽  
VITOR NAGAI YAMAKI ◽  
RENAN KLEBER COSTA TEIXEIRA ◽  
...  

ABSTRACT Objective: to evaluate the effects of blocking the regulation of vascular tone on the ischemia and reperfusion syndrome in rats through the use of lidocaine in the postconditioning technique. Methods: we randomized 35 rats into seven groups of five animals: Group 1- Control; Group 2- Ischemia and Reperfusion; Group 3- Ischemia, Reperfusion and Saline; Group 4- Ischemic Postconditioning; Group 5- Ischemic Postconditioning and Saline; Group 6- Lidocaine; Group 7- Ischemic Postconditioning and Lidocaine. Except for the control group, all the others were submitted to renal ischemia for 30 minutes. In postconditioning groups, we performed ischemia and reperfusion cycles of five minutes each, applied right after the main ischemia. In saline and lidocaine groups, we instilled the substances at a rate of two drops per minute. To compare the groups, we measured serum levels of urea and creatinine and also held renal histopathology. Results: The postconditioning and postconditioning + lidocaine groups showed a decrease in urea and creatinine values. The lidocaine group showed only a reduction in creatinine values. In histopathology, only the groups submitted to ischemic postconditioning had decreased degree of tubular necrosis. Conclusion: Lidocaine did not block the effects of postconditioning on renal ischemia reperfusion syndrome, and conferred better glomerular protection when applied in conjunction with ischemic postconditioning.


2003 ◽  
Vol 66 (5) ◽  
pp. 860-865 ◽  
Author(s):  
L. RIZZI ◽  
M. SIMIOLI ◽  
P. RONCADA ◽  
A. ZAGHINI

Ninety-six laying hens were allocated to four groups administered different diets (group 0-0 received a complete diet, group 0-AF received a diet supplemented with 2.5 ppm of aflatoxin B1 [AFB1], group 2-0 received a diet supplemented with 2% clinoptilolite [CPL], and group 2-AF received a diet supplemented with 2% CPL and 2.5 ppm of AFB1) for 4 weeks to evaluate the effect of AFB1 and/or CPL on egg quality and the ability of CPL to interact with the oral administration of AFB1. The possible effects of AFB1 on cytochrome P450–dependent hepatic mixed-function oxygenase (MFO) activities were also evaluated. Mycotoxin reduced yolk weight, while CPL influenced albumen percentage relative to that of eggs laid by chickens in group 0-AF. Eggs laid by chickens in groups 0-AF and 2-AF had stronger shells and weighed less than the eggs of other groups. The eggs of treated groups were lighter in color than those of the control group (P &lt; 0.01), and the tendency to yellowness in eggs was increased by CPL, probably through the affinity of red pigments for adsorbents and a consequent prevalence of yellow tonality. Color parameters might be connected with AFB1's interference with lipid metabolism and pigment deposition. The livers of hens in groups 0-AF and 2-AF showed very low mycotoxin concentrations that were significantly different (P &lt; 0.01). The highest levels observed were those in the livers of the hens receiving the diet supplemented with the mycotoxin alone. AFB1 did not exert any significant effects on the hepatic MFO activities examined.


1986 ◽  
Vol 250 (4) ◽  
pp. E352-E361 ◽  
Author(s):  
W. M. Barron ◽  
J. Schreiber ◽  
M. D. Lindheimer

Effects of sex steroids on osmoregulation were studied in intact and ovariectomized Sprague-Dawley rats treated for 2 wk with subcutaneously implanted hormone pellets containing 0.5 mg 17 beta-estradiol (E2) alone (group 1) or combined with 50 mg progesterone (PG; group 2) and 5.0 mg E2 alone (group 3) combined with PG (group 4). An additional group (5) of animals was given 14 daily injections with 100 micrograms/100 g body weight of E2. Controls for each group received vehicle alone. There were no alterations in basal plasma osmolality (Posmol) or vasopressin (PAVP), except for group 3 in which a small (2.5 mosmol/kg) decrement in Posmol was observed. However, mean PNa was decreased (0.9-3.4 meq/l) in hormone-treated rats, and alterations in Pglucose and/or Purea could not explain the Na-osmolal discrepancy. Intraperitoneal hypertonic saline resulted in stepwise increases in both Posmol and PAVP. Regression analysis of PAVP on Posmol demonstrated similar osmotic thresholds for AVP release in estrogen and control rats, but the slope (sensitivity of the response) was significantly (P less than 0.005) greater in hormone-treated animals. In contrast, the PAVP response to isosmotic volume depletion was not altered by estrogen. The enhanced response to osmotic stimuli could not be explained by alterations in plasma volume or pituitary AVP content and differed from PAVP -Posmol relationships observed by us previously in gravid rats. In other experiments Posmol and PAVP were similar during all stages of the estrus cycle, while Posmol was approximately equal to 10 mosmol/kg lower in 21-day gravid rats. These data demonstrate that, although estradiol has little effect on basal osmoregulation or hemodynamically mediated AVP release, PAVP responses to osmotic stimuli are markedly enhanced. These osmoregulatory effects, however, differ from those observed during rodent gestation.


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