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Thymoquinone attenuates diethylnitrosamine induction of hepatic carcinogenesis through antioxidant signaling

Mohamed M Sayed-Ahmed1, Abdulaziz M Aleisa2, Salim S Al-Rejaie2

  • 1Department of Pharmacology; College of Pharmacy; King Saud University; Riyadh Kingdom of Saudi Arabia. sayedahmedmm@hotmail.com

Oxidative Medicine and Cellular Longevity
|October 26, 2010
PubMed

Insights

Thymoquinone (TQ) from Nigella sativa prevents liver cancer initiation in rats. TQ supplementation reversed harmful biochemical and cellular changes caused by diethylnitrosamine (DENA), reducing oxidative stress and preserving antioxidant enzymes.

Area of Science:

  • Hepatocellular carcinoma research
  • Chemoprevention strategies
  • Oxidative stress and carcinogenesis

Background:

  • Hepatocellular carcinoma (HCC) is a major cause of cancer mortality, with chemoprevention being a key strategy.
  • Nigella sativa derived thymoquinone (TQ) possesses potent antioxidant properties.
  • Diethylnitrosamine (DENA) is a known hepatocarcinogen used to induce liver cancer in experimental models.

Purpose of the Study:

  • To investigate the chemopreventive potential of thymoquinone (TQ) against diethylnitrosamine (DENA)-induced hepatocarcinogenesis in rats.
  • To evaluate the effect of TQ on oxidative stress markers and antioxidant enzyme activity and expression during liver cancer initiation.

Main Methods:

  • Male Wistar albino rats were divided into four groups: control, TQ-treated, DENA-induced, and DENA + TQ-treated.
  • Biochemical markers (ALT, ALP, bilirubin, TBARS, NOx), antioxidant enzyme activities (GSH, GSHPx, GST, CAT), and gene expression were analyzed in liver tissues.
  • Histopathological examination was performed to assess liver damage.

Main Results:

  • DENA administration significantly elevated liver enzymes, oxidative stress markers (TBARS, NOx), and decreased antioxidant levels (GSH, GSHPx, GST, CAT).
  • DENA also reduced the mRNA expression of antioxidant enzymes (GSHPx, GST, CAT) and caused severe liver histopathological damage.
  • TQ supplementation effectively normalized all biochemical and histopathological alterations induced by DENA, preserving antioxidant enzyme activity and expression.

Conclusions:

  • DENA-induced hepatocarcinogenesis is associated with decreased mRNA expression of key antioxidant enzymes.
  • Thymoquinone (TQ) supplementation demonstrates significant chemopreventive effects against DENA-induced liver cancer initiation.
  • TQ exerts its protective effects by mitigating oxidative stress and maintaining the integrity of antioxidant defense systems.
Keywords:
diethylnitrosaminegene expressionhepatic carcinogenesisthymoquinone

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