Doxorubicin Toxicity can be Ameliorated during Antioxidant L-Carnitine Supplementation

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.

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Inhibition of Gene Expression of Organic Cation/Carnitine Transporter and Antioxidant Enzymes in Oxazaphosphorines-Induced Acute Cardiomyopathic Rat Models

Oxidative Medicine and Cellular Longevity ◽

10.1155/2012/452902 ◽

2012 ◽

Vol 2012 ◽

pp. 1-13 ◽

Cited By ~ 2

Author(s):

Mohamed M. Sayed-Ahmed ◽

Meshan Lafi Aldelemy ◽

Mohamed M. Hafez ◽

Othman A. Al-Shabanah

Keyword(s):

Gene Expression ◽

Protein Expression ◽

Organic Cation ◽

Albino Rats ◽

Carnitine Supplementation ◽

Antioxidant Genes ◽

Cardiac Tissues ◽

Carnitine Transporter ◽

Mrna And Protein Expression ◽

Wistar Albino Rats

It is well documented that high therapeutic doses of oxazaphosphorines, cyclophosphamide (CP) and ifosfamide (IFO), are associated with cardiomyopathy. This study investigated whether oxazaphosphorines alter the expression of organic cation/carnitine transporter (OCTN2) and antioxidant genes and if so, whether these alterations contribute to CP and IFO-induced cardiotoxicity. Adult male Wistar albino rats were assigned to one of six treatment groups namely, control, L carnitine, CP, IFO, CP plus L carnitine and IFO plus L carnitine. In cardiac and kidney tissues, CP and IFO significantly decreased mRNA and protein expression of OCTN2. Oxazaphosphorines significantly increased serum acyl-carnitine/free carnitine ratio and urinary carnitine excretion and significantly decreased total carnitine in cardiac tissues. Interestingly, carnitine supplementation completely reversed the biochemical and gene expression changes-induced by oxazaphosphorines to the control values, except OCTN2 expression remained inhibited by IFO. Data from this study suggest that: (1) Oxazaphosphorines decreased myocardial carnitine content following the inhibition of OCTN2 mRNA and protein expression in cardiac tissues. (2) Oxazaphosphorine therapy increased urinary loss of carnitine secondary to the inhibition of OCTN2 mRNA and protein expression in proximal tubules of the kidney. (3) Carnitine supplementation attenuates CP but not IFO-induced inhibition of OCTN2 mRNA and protein expression in heart and kidney tissues.

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Thymoquinone Attenuates Diethylnitrosamine Induction of Hepatic Carcinogenesis Through Antioxidant Signaling

Oxidative Medicine and Cellular Longevity ◽

10.4161/oxim.3.4.12714 ◽

2010 ◽

Vol 3 (4) ◽

pp. 254-261 ◽

Cited By ~ 79

Author(s):

Mohamed M. Sayed-Ahmed ◽

Abdulaziz M. Aleisa ◽

Salim S. Al-Rejaie ◽

Abdulaziz A. Al-Yahya ◽

Othman A. Al-Shabanah ◽

...

Keyword(s):

Liver Cancer ◽

Mrna Expression ◽

Nigella Sativa ◽

Antioxidant Properties ◽

Cancer Chemoprevention ◽

Thiobarbituric Acid ◽

Albino Rats ◽

Hepatic Carcinogenesis ◽

Group 2 ◽

Wistar Albino Rats

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.

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The Curative Effect of Berberine Nanoparticles and Cisplatin Combination Therapies Against Hepatocarcinogenesis-Induced By N-Nitroso-Diethylamine In Male Rat

JOURNAL OF ADVANCES IN BIOLOGY ◽

10.24297/jab.v11i1.7207 ◽

2018 ◽

Vol 11 (1) ◽

pp. 2180-2200

Author(s):

Nema Abdelhameed Mohamed ◽

Awatef Mohamed Ali ◽

Doaa Ahmed Ghareeb ◽

Adham Rashed Mohamed ◽

Yasmin Mohamed Elmokhtar

Keyword(s):

Gene Expression ◽

Male Rats ◽

Male Rat ◽

Control Group ◽

Albino Rats ◽

Group 4 ◽

Ccl4 Treatment ◽

Group 5 ◽

Group 2 ◽

Wistar Albino Rats

This study aimed to investigate whether berberine nanoparticles (BBR-NPs) and/or cisplatin supplementation could prevent hepatocarcinogenesis-induced by N-nitroso-diethylamine (DENA) in male rats. Male Wistar albino rats were divided into five groups; Group 1: Control; Group 2: DENA-CCl4; Group 3: DENA-CCl4+Cisplatin; Group 4: DENA-CCl4+BBR-NPs; Group 5: DENA-CCl4+Cisplatin+BBR-NPs. DENA-CCl4 significantly increase AST, ALT, ALP, LDH, GGT, AFP activities and total bilirubin, while, 5, NT, total protein and albumin decreased. DENA-CCl4 treatment caused increment in MDA levels and reduction in SOD, CAT, GPx and GSH in liver tissues. Moreover, DENA-CCl4 increase the gene expression of ADAM17 and TNF-Î± however, P53 was declined. In addition, DENA-CCl4 caused severe histopathological lesions in the liver tissue. Interestingly, administration of berberine nanoparticles alone or in combination with cisplatin improves the hepatocarcinogenesis induced by DENA-CCl4 on the physiological, biochemical, molecular and histological levels by decreasing oxidative stress and preserving gene expression of ADAM17, TNF-Î± and P53. The present findings suggest that BBR-NPs with cisplatin might offer a promising strategy for the prevention of liver cancer.

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Triazophos induced neuro-splenic toxicity and evaluation of antioxidative potential of aqueous Broccoli extract in Wistar albino rats

Journal of Applied and Natural Science ◽

10.31018/jans.v13i2.2644 ◽

2021 ◽

Vol 13 (2) ◽

pp. 616-626

Author(s):

Dharmender Sharma ◽

Gurinder Kaur Sangha

Keyword(s):

Histological Study ◽

Control Group ◽

Albino Rats ◽

White Pulp ◽

Protective Effects ◽

Glutathione S Transferase ◽

Group 4 ◽

Group 5 ◽

Group 2 ◽

Wistar Albino Rats

The present investigation was carried out to assess the antioxidative potential of Broccoli sprouts aqueous extract (BE) against triazophos (TZ) induced oxidative stress (OS) in brain and spleen. In the experimental setup, six groups of rats were formed; Control (group 1), BE (group 2), TZ (group 3), and also BE+TZ groups such as BE1 (group 4), BE2 (group 5) and BE3 (group 6) groups. Rats were orally intubated for 30 days as per experimental design. After sacrifice, OS biomarkers viz; catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and lipid peroxidation (LPO) levels were determined in brain and spleen. Acetylcholinesterase (AChE) activity was observed in plasma and brain samples. Histological study of the spleen in TZ rats showed increased thickness of capsule, congestion and hypocellularity in follicles of spleen’s white pulp and the histoarchitecture was restored in TZ+BE group rats. TZ caused degenerative changes in brain histology and rats showed mild congestion along with haemorrhage in the cerebral cortex. Results suggest that TZ exposure is associated with neural toxicity along with altered spleen stress biomarkers, which further corroborates with histopathological findings. It is inferred that BE exerts multi-mechanistic protective effects against TZ induced neuro-splenic toxicity which is attributable to its protective antioxidant actions.

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Biochemical Studies on Phenylhydrazine Induced Experimental Anemic Albino Rats

Journal of Universal College of Medical Sciences ◽

10.3126/jucms.v3i1.13258 ◽

2015 ◽

Vol 3 (1) ◽

pp. 41-47

Author(s):

Nirjala Laxmi Madhikarmi ◽

Kora Rudraiah Siddalinga Murthy

Keyword(s):

Lipid Peroxidation ◽

Lipid Hydroperoxide ◽

Thiobarbituric Acid ◽

Albino Rats ◽

Enzymatic Antioxidants ◽

Medical Sciences ◽

Thiobarbituric Acid Reactive Substances ◽

Biochemical Studies ◽

Healthy Control ◽

Wistar Albino Rats

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

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Development of the spine following pinealectomy or sensorimotor cortical area damage

Acta Veterinaria Brno ◽

10.2754/avb201382040411 ◽

2013 ◽

Vol 82 (4) ◽

pp. 411-414

Author(s):

Richard Chaloupka ◽

Milan Dvořák ◽

František Tichý ◽

Jiří Veselý ◽

Alois Nečas

Keyword(s):

Cortical Area ◽

Mean Value ◽

Albino Rats ◽

Sham Operation ◽

Growing Rats ◽

Growing Rat ◽

Group 2 ◽

Wistar Albino Rats ◽

New Hypothesis ◽

Group 1

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.

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Effects of erdosteine on cyclosporin-A-induced nephrotoxicity

Human & Experimental Toxicology ◽

10.1177/0960327111417907 ◽

2011 ◽

Vol 31 (6) ◽

pp. 565-573 ◽

Cited By ~ 13

Author(s):

M Tutanc ◽

V Arica ◽

N Yılmaz ◽

A Nacar ◽

I Zararsiz ◽

...

Keyword(s):

Oxidative Stress ◽

Cyclosporin A ◽

Protective Role ◽

Control Group ◽

Albino Rats ◽

Protective Mechanism ◽

Antioxidant Parameters ◽

Group 2 ◽

Wistar Albino Rats

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.

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Tetracalcium Phosphate Treatment on Experimental Fracture Model in Rats

10.21203/rs.3.rs-94009/v1 ◽

2020 ◽

Author(s):

Burak Kaymaz ◽

Onur Yılmaz ◽

Ali Osman Taşova ◽

Doğukan Anapa

Keyword(s):

Fracture Healing ◽

Bone Union ◽

Albino Rats ◽

Left Femur ◽

Tetracalcium Phosphate ◽

Significant Difference ◽

Additional Procedure ◽

Phosphate Treatment ◽

Group 2 ◽

Wistar Albino Rats

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.

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Can N-Acetylcysteine Preserve Peritoneal Function and Morphology in Encapsulating Peritoneal Sclerosis?

Peritoneal Dialysis International ◽

10.1177/089686080902902s41 ◽

2009 ◽

Vol 29 (2_suppl) ◽

pp. 202-205 ◽

Cited By ~ 8

Author(s):

Devrim Bozkurt ◽

Ender Hur ◽

Burcu Ulkuden ◽

Murat Sezak ◽

Hasim Nar ◽

...

Keyword(s):

Peritoneal Dialysis ◽

Cell Count ◽

Degradation Products ◽

Isotonic Saline ◽

Control Group ◽

Albino Rats ◽

Peritoneal Fibrosis ◽

Beneficial Effects ◽

Group 2 ◽

Wistar Albino Rats

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.

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