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Thymoquinone attenuates cisplatin-induced hepatotoxicity via nuclear factor kappa-β.

Al-Malki AL, Sayed AA - BMC Complement Altern Med (2014)

Bottom Line: The antioxidant enzyme activities and reduced glutathione (GSH) contents were significantly decreased while the levels of malondialdehyde (MDA) significantly increased.The antioxidant enzyme activities (glutathione peroxidase and glutathione -S transferase) of the rat livers were markedly increased while MDA was reduced as a result of TQ administration.In addition, the expression of TNF-α, iNOS, and IL-1β were markedly reduced.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Faculty of Science, King Abdulaziz University, P,O Box 80203, Jeddah, Saudi Arabia. alalmalki@kau.edu.sa.

ABSTRACT

Background: Cisplatin (CP) is known as a potent anti-cancer drug. The most therapeutic adverse effect of CP is induced hepatotoxicity. In the present study, the protective effect of thymoquinone (TQ) on CP-induced hepatotoxicity was studied.

Methods: Wistar rats were divided into three groups (15 rats each). Group 1 served as the control group. Group 2 rats were injected ip with a single dose of CP (12 mg/kg b.w, i.p.). Group 3 rats were orally pre-treated with TQ (500 mg. kg(-1). day(-1)) for one month, then the animals were injected i.p with CP 12 mg.kg(-1).

Results: The beneficial effects of TQ with its antioxidant/anti-inflammatory effects were observed. Injection of rats with CP markedly affected the liver functions and histopathological changes. The antioxidant enzyme activities and reduced glutathione (GSH) contents were significantly decreased while the levels of malondialdehyde (MDA) significantly increased. The electromobility shift assay (EMSA) showed a significant activation of NF-κB-p65 in the rat liver injected with CP. Furthermore, the expression and concentrations of inflammatory tumor necrosis factor (TNF-α), nitric oxide synthetase (iNOS), and interleukin (IL-1β) were markedly elevated in the CP injected rats. The administration of TQ improved all the altered functions, histopathology of the liver and attenuated the activated NF-κB. The antioxidant enzyme activities (glutathione peroxidase and glutathione -S transferase) of the rat livers were markedly increased while MDA was reduced as a result of TQ administration. In addition, the expression of TNF-α, iNOS, and IL-1β were markedly reduced.

Conclusion: It was concluded that, TQ has potential benefits in the prevention of the onset and progression of CP induced hepatotoxicity.

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Effect of CP on IL1-β, TNF-α and iNOS expression (A). The relative intensity of the bands is represented in (B) Data are the mean ± S.D. (n15); *P < 0.01, **P < 0.01 vs. control animals.
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Fig3: Effect of CP on IL1-β, TNF-α and iNOS expression (A). The relative intensity of the bands is represented in (B) Data are the mean ± S.D. (n15); *P < 0.01, **P < 0.01 vs. control animals.

Mentions: As a result of oxidative stress, NF-κB-p65 was markedly activated in the cisplatin treated animals compared with the normal control. Administration of TQ resulted in a significant reduction of the of NF-κB-p65 activation. The levels of TNFα and IL-1β were significantly and dose dependently elevated in the CP treated rats (group 2) as indicated in Figure 1B and C. The elevated levels of TNFα and IL-1β were significantly reduced as a result of TQ administration (Figure 3).


Thymoquinone attenuates cisplatin-induced hepatotoxicity via nuclear factor kappa-β.

Al-Malki AL, Sayed AA - BMC Complement Altern Med (2014)

Effect of CP on IL1-β, TNF-α and iNOS expression (A). The relative intensity of the bands is represented in (B) Data are the mean ± S.D. (n15); *P < 0.01, **P < 0.01 vs. control animals.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4129109&req=5

Fig3: Effect of CP on IL1-β, TNF-α and iNOS expression (A). The relative intensity of the bands is represented in (B) Data are the mean ± S.D. (n15); *P < 0.01, **P < 0.01 vs. control animals.
Mentions: As a result of oxidative stress, NF-κB-p65 was markedly activated in the cisplatin treated animals compared with the normal control. Administration of TQ resulted in a significant reduction of the of NF-κB-p65 activation. The levels of TNFα and IL-1β were significantly and dose dependently elevated in the CP treated rats (group 2) as indicated in Figure 1B and C. The elevated levels of TNFα and IL-1β were significantly reduced as a result of TQ administration (Figure 3).

Bottom Line: The antioxidant enzyme activities and reduced glutathione (GSH) contents were significantly decreased while the levels of malondialdehyde (MDA) significantly increased.The antioxidant enzyme activities (glutathione peroxidase and glutathione -S transferase) of the rat livers were markedly increased while MDA was reduced as a result of TQ administration.In addition, the expression of TNF-α, iNOS, and IL-1β were markedly reduced.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Faculty of Science, King Abdulaziz University, P,O Box 80203, Jeddah, Saudi Arabia. alalmalki@kau.edu.sa.

ABSTRACT

Background: Cisplatin (CP) is known as a potent anti-cancer drug. The most therapeutic adverse effect of CP is induced hepatotoxicity. In the present study, the protective effect of thymoquinone (TQ) on CP-induced hepatotoxicity was studied.

Methods: Wistar rats were divided into three groups (15 rats each). Group 1 served as the control group. Group 2 rats were injected ip with a single dose of CP (12 mg/kg b.w, i.p.). Group 3 rats were orally pre-treated with TQ (500 mg. kg(-1). day(-1)) for one month, then the animals were injected i.p with CP 12 mg.kg(-1).

Results: The beneficial effects of TQ with its antioxidant/anti-inflammatory effects were observed. Injection of rats with CP markedly affected the liver functions and histopathological changes. The antioxidant enzyme activities and reduced glutathione (GSH) contents were significantly decreased while the levels of malondialdehyde (MDA) significantly increased. The electromobility shift assay (EMSA) showed a significant activation of NF-κB-p65 in the rat liver injected with CP. Furthermore, the expression and concentrations of inflammatory tumor necrosis factor (TNF-α), nitric oxide synthetase (iNOS), and interleukin (IL-1β) were markedly elevated in the CP injected rats. The administration of TQ improved all the altered functions, histopathology of the liver and attenuated the activated NF-κB. The antioxidant enzyme activities (glutathione peroxidase and glutathione -S transferase) of the rat livers were markedly increased while MDA was reduced as a result of TQ administration. In addition, the expression of TNF-α, iNOS, and IL-1β were markedly reduced.

Conclusion: It was concluded that, TQ has potential benefits in the prevention of the onset and progression of CP induced hepatotoxicity.

Show MeSH
Related in: MedlinePlus