Thymoquinone Attenuates Diethylnitrosamine Induction of Hepatic Carcinogenesis Through Antioxidant Signaling

Abstract

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 sativa derived-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.

Blueberry treatment attenuated cirrhotic and preneoplastic lesions and oxidative stress in the liver of diethylnitrosamine-treated rats

“…38 Several researchers have reported increased oxidative stress parameters such as MDA, DC, PC, and DNA damage together with decreased non-enzymatic and enzymatic antioxidants in the liver due to DEN treatment. [3][4][5][6]34,39,40 In the current study, increases in hepatic MDA, DC, and PC levels and decreases in SOD, CAT, and GSH-Px activities were due to DEN treatment. However, GSH levels and GST activities were observed as increased due to DEN treatment.…”

Antioxidant potential of Thymoquinone against Arsenic mediated neurotoxicity

“…in brain in the treatment groups, as TQ induces greater coupling of electrophilic intermediates with GSH. 42 The plausible mechanisms might be related to the ability of TQ to suppress oxidant formation and maintain the GSH ratio. Similarly, NP-SH levels also increased significantly in brain when exposed to As.…”

Thymoquinone improves aging-related endothelial dysfunction in the rat mesenteric artery

“…TQ has also been shown to improve oxidative stress in streptozotocin-induced diabetic rats (Sankaranarayanan and Pari 2011) and to attenuate the cyclophosphamide-induced cardiotoxicity in rats, at least in part, by decreasing oxidative stress and improving the mitochondrial function (Nagi et al 2011). TQ attenuated also the diethylnitrosamineinduced hepatic carcinogenesis through an antioxidant effect (Sayed-Ahmed et al 2010), the high cholesterol-induced oxidative stress in the rabbit liver (Attia et al 2010), and the mercuric chloride-induced renal oxidative damage in rats (Fouda et al 2008).…”