scholarly journals Thymoquinone Attenuates Diethylnitrosamine Induction of Hepatic Carcinogenesis Through Antioxidant Signaling

2010 ◽  
Vol 3 (4) ◽  
pp. 254-261 ◽  
Author(s):  
Mohamed M. Sayed-Ahmed ◽  
Abdulaziz M. Aleisa ◽  
Salim S. Al-Rejaie ◽  
Abdulaziz A. Al-Yahya ◽  
Othman A. Al-Shabanah ◽  
...  

Hepatocellular carcinoma accounts for about 80–90% of all liver cancer and is the fourth most common cause of cancer mortality. Although there are many strategies for the treatment of liver cancer, chemoprevention seems to be the best strategy for lowering the incidence of this disease. Therefore, this study has been initiated to investigate whether thymoquinone (TQ),Nigella sativaderived-compound with strong antioxidant properties, supplementation could prevent initiation of hepatocarcinogenesis-induced by diethylnitrosamine (DENA), a potent initiator and hepatocarcinogen, in rats. Male Wistar albino rats were divided into four groups. Rats of Group 1 received a single intraperitoneal (I.P.) injection of normal saline. Animals in Group 2 were given TQ (4 mg/kg/day) in drinking water for 7 consecutive days. Rats of Group 3 were injected with a single dose of DENA (200 mg/kg, I.P.). Animals in Group 4 were received TQ and DENA. DENA significantly increased alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin, thiobarbituric acid reactive substances (TBARS) and total nitrate/nitrite (NOx) and decreased reduced glutathione (GSH), glutathione peroxidase (GSHPx), glutathione-s-transferase (GST) and catalase (CAT) activity in liver tissues. Moreover, DENA decreased gene expression of GSHPx, GST and CAT and caused severe histopathological lesions in liver tissue. Interestingly, TQ supplementation completely reversed the biochemical and histopathological changes induced by DENA to the control values. In conclusion, data from this study suggest that: (1) decreased mRNA expression of GSHPx, CAT and GST during DENA-induced initiation of hepatic carcinogenesis, (2) TQ supplementation prevents the development of DENA-induced initiation of liver cancer by decreasing oxidative stress and preserving both the activity and mRNA expression of antioxidant enzymes.

2010 ◽  
Vol 3 (6) ◽  
pp. 428-433 ◽  
Author(s):  
Othman A. Alshabanah ◽  
Mohamed M. Hafez ◽  
Mohamed M. Al-Harbi ◽  
Zeinab K. Hassan ◽  
Salim S. Al Rejaie ◽  
...  

Doxorubicin is an antibiotic broadly used in treatment of different types of solid tumors. The present study investigates whether L-carnitine, antioxidant agent, can reduce the hepatic damage induced by doxorubicin. Male Wistar albino rats were divided into six groups: group 1 was intraperitoneal injected with normal saline for 10 consecutive days; group 2, 3 and 4 were injected every other day with doxorubicin (3 mg/kg, i.p.), to obtain treatments with cumulative doses of 6, 12 and 18 mg/kg. The fifth group was injected with L-carnitine (200 mg/kg, i.p.) for 10 consecutive days and the sixth group was received doxorubicin (18 mg/kg) and L-carnitine (200 mg/kg). High cumulative dose of doxorubicin (18 mg/kg) significantly increases the biochemical levels of alanine transaminase, alkaline phosphatase, total bilirubin, thiobarbituric acid reactive substances (TBARs), total nitrate/nitrite (NOx) p < 0.05 and decrease in glutathione (GSH ), superoxide dismutase (SOD), glutathione peroxidase (GSHP x), glutathione-s-transferase (GST), glutathione reductase (GR) and catalase (CAT) activity p < 0.05. The effect of doxorubicin on the activity of antioxidant genes was confirmed by real time PCR in which the expression levels of these genes in liver tissue were significantly decrease compared to control p < 0.05. Interestingly, L-carnitine supplementation completely reversed the biochemical and gene expression levels induced by doxorubicin to the control values. In conclusion, data from this study suggest that the reduction of antioxidant defense during doxorubicin administration resulted in hepatic injury could be prevented by L-carnitine supplementation by decreasing the oxidative stress and preserving both the activity and gene expression level of antioxidant enzymes.


2015 ◽  
Vol 3 (1) ◽  
pp. 41-47
Author(s):  
Nirjala Laxmi Madhikarmi ◽  
Kora Rudraiah Siddalinga Murthy

INTRODUCTION: The present study evaluated the modulatory effects of diphenylhydrazine induced experimental wistar albino rats and also to assess various biochemical parameters in whole blood and red blood cell lysate.MATERIALAND METHODS: Twenty male albino rats weighing 180-200 gm were selected for the study and divided in two groups; ten phenylhydrazine dihydrochloride (PHZ) induced anemia and ten healthy control. Thiobarbituric acid reactive substances and lipid hydroperoxide were measured as lipid peroxidation parameter. The antioxidant vitamins A, C and E and enzymatic antioxidants; catalase, glutathione peroxidase and superoxide dismutase were also assessed.RESULTS: Phenylhydrazine induced anemic rats showed a significant increase in the lipid peroxidation and decrease in the antioxidants as compared to healthy rats.CONCLUSION: The study concludes that phenylhydrazine induced experimental anemic albino rats showed increased oxidative stress than compared with healthy albino rats.Journal of Universal College of Medical Sciences Vol. 3, No. 1, 2015: 41-47 


2013 ◽  
Vol 82 (4) ◽  
pp. 411-414
Author(s):  
Richard Chaloupka ◽  
Milan Dvořák ◽  
František Tichý ◽  
Jiří Veselý ◽  
Alois Nečas

The aim of this experimental study was to assess the spine development in growing rats following pinealectomy or partial sensorimotor cortical area damage. A total of 68 Wistar albino rats (Rattus norvegicus v. alba f. domestica) aged 3–4 weeks were divided into four groups. In group 1 (n = 22) pinealectomy was performed, in group 2 (n = 24) the sensorymotor cortical area 2 × 1 × 1 mm below the coronal suture was removed. Sham operation consisted of a craniotomy (n = 11) and a craniotomy with a durotomy (n = 11). All surgeries were performed from the left side. The rats were killed four months after surgery and radiography was then made. Scoliosis, C2-T7 lordosis and T7-S1 kyphosis were measured.The brains of rats after sensorimotor cortical area removal were isolated and investigated including histological examination (light microscope). Scoliosis of 9–14 degrees (mean value 10.8) was developed in five animals after pinealectomy; in rats after removal of the sensorimotor cortical area scoliosis of 10–24 degrees (mean value 15.9) was observed in eight animals. The scoliotic curves were non structural. Our results indicate the importance of cortical area damage, together with craniotomy and durotomy in the development of growing rat spine. These damages could cause a disorder of balance between smaller inhibitory and greater facilitating area of central nervous system, controlling the muscular tone and resulting in the development of increased lordosis and kyphosis and non structural scoliosis due to muscle imbalance. Thus the new hypothesis of scoliosis aetiology was introduced.


2011 ◽  
Vol 31 (6) ◽  
pp. 565-573 ◽  
Author(s):  
M Tutanc ◽  
V Arica ◽  
N Yılmaz ◽  
A Nacar ◽  
I Zararsiz ◽  
...  

Aim: In cyclosporin-A (CsA)-induced toxicity, oxidative stress has been implicated as a potential responsible mechanism. Therefore, we aimed to investigate the protective role of erdosteine against CsA-induced nephrotoxicity in terms of tissue oxidant/antioxidant parameters and light microscopy in rats. Materials and methods: Wistar albino rats were randomly separated into four groups. Group 1 rats treated with sodium chloride served as the control, group 2 rats were treated with CsA, group 3 with CsA plus erdosteine, and group 4 with erdosteine alone. Animals were killed and blood samples were analyzed for blood urea nitrogen (BUN), serum creatinine (Cr), uric acid (UA), total protein (TP), and albumin (ALB) levels. Kidney sections were analyzed for malondialdehyde (MDA) and nitric oxide (NO) levels and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities, as well as for histopathological changes. Results: In the CsA group, MDA, GSH-Px, BUN, and Cr levels were increased. The TP and ALB levels were decreased. These changes had been improved by erdosteine administration. Other biochemical parameters did not show any significant change. Conclusion: These results indicate that erdosteine produces a protective mechanism against CsA-induced nephrotoxicity and suggest a role of oxidative stress in pathogenesis.


2020 ◽  
Author(s):  
Burak Kaymaz ◽  
Onur Yılmaz ◽  
Ali Osman Taşova ◽  
Doğukan Anapa

Abstract Background: Studies have shown that bioactive cements have beneficial bone-forming effects. Our objective in the present study is to investigate the efficacy of tetracalcium phosphate (TTCP) on fracture healing in rat femur.Materials and methods: Forty-two female Wistar Albino rats randomized into two groups (groups 1 and 2, n=21 for each). The left femur of all animals was fractured by osteotomy after deep anesthesia with ketamine. Additional procedure was not applied to the rats in group 1. Rats in Group 2, following osteotomy were applied to the fracture line approximately 2 cc TTCP. The animals were sacrificed on the 1st, 2nd and 3rd post-operative weeks (each week 7 animals were sacrificed from each group) and the broken femur were removed. The femur were examined first radiographically and second, histopathologically.Results: Radiologically, callus maturity and bone union increased with time in both groups. But no significant differences were found regarding callus maturity and bone union in weekly comparisons (Anteroposterior plain: p:0.53, p:0.37, p:0.42, Lateral plain p:0.26, p:0.42, p:0.87). Histopathologically, the fractures healed normally as the weeks progressed in both groups. In the comparison of both groups, no significant difference was found outside the 1st week, although the histological scores of group 2, who were treated for all weeks, were higher in terms of fracture healing (p:0,024, p:104,p:462).Conclusions: Although no significant difference was found in the comparison of both groups except for the first week, the histological scores of the group 2 who received TTCP in all weeks were higher in terms of fracture healing. According to the results of this study, we think that TTCP can be useful especially in the early stages of fracture healing.


2009 ◽  
Vol 29 (2_suppl) ◽  
pp. 202-205 ◽  
Author(s):  
Devrim Bozkurt ◽  
Ender Hur ◽  
Burcu Ulkuden ◽  
Murat Sezak ◽  
Hasim Nar ◽  
...  

Long-term use of the peritoneum as a dialysis membrane results in progressive irreversible dysfunction, described as peritoneal fibrosis. Oxidative stress during peritoneal dialysis has been established in many studies. Generation of reactive oxygen species (ROS) by conventional peritoneal dialysis solutions, regardless of whether produced by high glucose, angiotensin II, or glucose degradation products may be responsible for progressive membrane dysfunction. The well-known antioxidant molecule N-acetylcysteine (NAC) is capable of direct scavenging of ROS. The aim of the present study was to investigate the effect of NAC therapy on both progression and regression of encapsulating peritoneal sclerosis (EPS). We divided 49 nonuremic Wistar albino rats into four groups: Control group—2 mL isotonic saline intraperitoneally (IP) daily for 3 weeks; CG group—2 mL/200 g 0.1% chlorhexidine gluconate (CG) and 15% ethanol dissolved in saline injected IP daily for a total of 3 weeks; Resting group—CG (weeks 1 – 3), plus peritoneal resting (weeks 4 – 6); NAC-R group—CG (weeks 1 – 3), plus 2 g/L NAC (weeks 4 – 6). At the end of the experiment, all rats underwent a 1-hour peritoneal equilibration test with 25 mL 3.86% PD solution. Dialysate-to-plasma ratio (D/P) urea, dialysate white blood cell count (per cubic milliliter), ultrafiltration (UF) volume, and morphology changes of parietal peritoneum were examined. The CG group progressed to encapsulating peritoneal sclerosis, characterized by loss of UF, increased peritoneal thickness, inflammation, and ultimately, development of fibrosis. Resting produced advantages only in dialysate cell count; with regard to vascularity and dialysate cell count, NAC was more effective than was peritoneal rest. Interestingly, we observed no beneficial effects of NAC on fibrosis. That finding may be a result of our experimental severe peritoneal injury model. However, decreased inflammation and vascularity with NAC therapy were promising results in regard to membrane protection.


2004 ◽  
Vol 20 (6-10) ◽  
pp. 141-147 ◽  
Author(s):  
Alpaslan Terzi ◽  
Mustafa Iraz ◽  
Semsettin Sahin ◽  
Atilla Ilhan ◽  
Nuri Idiz ◽  
...  

Rotenone, an insecticide of botanical origin, causes toxicity through inhibition of complex I of the respiratory chain in mitochondria. This study was undertaken to determine whether rotenone-induced liver oxidant injury is prevented by erdosteine, a mucolytic agent showing antioxidant properties. There were four groups of Male Wistar Albino rats: group one was untreated as control; the other groups were treated with erdosteine (50 mg/kg per day, orally), rotenone (2.5 mg/mL once and 1 mL/kg per day for 60 days, i.p.) or rotenone plus erdosteine, respectively. Rotenone treatment without erdosteine increased xanthine oxidase (XO) enzyme activity and also increased lipid peroxidation in liver tissue P < 0.05). The rats treated with rotenone plus erdosteine produced a significant decrease in lipid peroxidation and XO activities in comparison with rotenone group PB / 0.05). Erdosteine treatment with rotenone led to an increase in catalase (CAT) and superoxide dismutase (SOD) activities in comparison with the rotenone group PB / 0.05). There was no significant difference in nitric oxide (NO) level between groups. There were negative correlations between CAT activity and malondialdehyde (MDA) level (r= -0.934, P <0.05) with between CAT and SOD activities (r= -0.714, P <0.05), and a positive correlation between SOD activity and MDA level (r= 0.828, P <0.05) in rotenone group. In the rotenone plus erdosteine group, there was a negative correlation between XO activity and NO level in liver tissue (r= -0.833, P -0.05). In the light of these findings, erdosteine may be a protective agent for rotenone-induced liver oxidative injury in rats.


2016 ◽  
Vol 6 (2) ◽  
pp. 66
Author(s):  
ukpabiugo ukpabiugo ◽  
Jacinta Chigozie ◽  
Patrick Iwuanyanwu ◽  
kingsley Chukwuemeka ◽  
Monanu Okechukwu

Introduction: This study aimed to assess the effect of exposure to gasoline vapor (GV) on the histomorphology and biochemical markers of renal function in rats. Methods: Twenty-four mature Wistar Albino rats weighing 180–200 g were randomly divided into two groups (n = 12 per group). Animals in group 1 (G1) served as unexposed controls, while animals in group 2 (G2) were exposed to GV for 35 days. At the end of the exposure, the animals were sacrificed, and blood samples were collected for biochemical analysis while the kidneys were removed and processed for histopathological evaluation. Results: Serum biochemical markers of renal function in the exposed group differed significantly (p< 0.05) from the unexposed group in urea (45.16 ± 1.00mg/dl versus(vs) 13.20 ± 0.69 mg/dl), creatinine (1.16 ± 0.27mg/dl vs 0.38 ± 0.10mg/dl), uric acid (3.66 ± 0.82mmol/L vs 1.96 ± 0.08mmol/L), potassium (6.90 ± 0.27mmol/L vs 3.57 ± 0.26mmol/L), sodium (182.60 ± 3.21mmol/L vs 141.33 ± 10.46mmol/L), chloride (119.00 ± 1.58mmol/L vs 103.33 ± 2.07mmol/L), pH (6.82 ± 0.22 vs 7.38 ± 0.25), bicarbonate (16.60 ± 5.03mmol/L vs 26.50 ± 3.45mmol/L), and glucose (125.60 ± 16.23mg/ dl vs 83.33 ± 4.46mg/dl). Histopathological examination of kidney sections revealed areas of degenerative and necrotic changes in the glomerulus, tubules, and renal vasculature, particularly in the cortical portion of the kidney. Conclusion: Chronic exposure to gasoline compounds may be associated with significant structural and biochemical derangements in kidney function.


Author(s):  
Jonathan Esima ◽  
Abraham Zorte ◽  
O. Onwuli, Donatus ◽  
Waribo, Helen Anthony

Aim: Ibuprofen is analgesic, antipyretic and anti-inflammatory drug, which is widely used as a cheap over- the counter drug (OTC); however, this drug accompanies anti coagulation/anti platelets effects which sometimes might illicit adverse effects. In this study, we investigated effect of ibuprofen on prothrombin time (PT), activated partial thromboplastin time (aPTT) and platelet count using wistar albino rats. Methods: A total of 21 rats grouped into 3(control, acute and chronic exposure groups, with all consisting of 7 rats each) was used. The acute and chronic exposure group were given 0.7 mg of ibuprofen orally for 1 and 21 days, respectively. Blood sample was collected via cardiac puncture then analyzed. Results: PT was significantly higher in both group 2 and 3 (acute and chronic exposure, respectively) than that of the control. Acute exposure group showed the highest PT rise. A PTT was not significantly different between group 2 and 3 versus the control group. Platelet count was significantly lower in both group 2 and 3than that in the control group (p<0.05). Group 3 (chronic exposure) showed the lowest platelet count. Conclusion: Oral administration of ibuprofen affected coagulation parameters and a longer exposure reduce platelets count. A strictly prescription for this drug may be needed to prevent its indiscriminate use.


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