Suppressive effects of thymoquinone on the initiation stage of diethylnitrosamine hepatocarcinogenesis in rats

Abstract

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer‐related death globally. Chemoprevention is the most effective technique for reducing HCC incidence. Thymoquinone (TQ), the main bioactive constituent of Nigella sativa, exhibits anti‐inflammatory and antineoplastic activities against various cancers. Therefore, TQ was tested as an inhibitor of the initial phase of diethylnitrosamine (DEN)‐induced HCC in rats. Twenty‐four male Wistar albino rats were randomly placed into four equal groups. Group 1 received saline and acted as the negative control; Group 2 received TQ; Group 3 received DEN; and Group 4 received TQ for 7 days and DEN on the 8th day. After 24 h of fasting, blood samples were taken from the slaughtered rats. Additionally, each rat's liver was dissected and separated into two halves for histological and biochemical investigation. DEN‐induced hepatotoxicity was detected by elevated hepatic enzymes and HCC biomarkers reduced antioxidant and proapoptotic statuses. DEN administration caused a significant increase in the levels of glutathione, superoxide dismutase, malondialdehyde, caspase‐3, alpha‐fetoprotein (AFP), AFPL3, glypican 3, and the expression of BAX. However, DEN significantly decreased glutathione peroxidase, catalase, and CYP2E1 and the expression of BCl‐2. Furthermore, it caused histological changes and showed a strong positive GSH S‐transferase P expression in the hepatic parenchyma. Pretreatment with TQ prevented the histopathological and most of the biochemical changes and improved the antioxidant status. TQ supplementation appears to suppress the development of DEN‐initiated liver cancer by reducing oxidative stress, activating the intrinsic mitotic apoptosis pathway, and retaining the antioxidant enzymes.

The Role of Thymoquinone in Inflammatory Response in Chronic Diseases

“…A recent study showed that the application of TQ with inhibitors at the initial stage of diethylnitrosamine (DEN)-induced HCC in rats resulted in the prevention of carcinoma progression. TQ pretreatment in rats prevented histopathology and most of the biochemical changes and improved the antioxidant status [ 42 , 43 ]. TQ also induces HCC cell death, activates the ERK and p38 signaling pathways, and exhibits excellent anti-HCC potential under suitable p-ERK inhibition conditions [ 42 , 43 ].…”

“…TQ pretreatment in rats prevented histopathology and most of the biochemical changes and improved the antioxidant status [ 42 , 43 ]. TQ also induces HCC cell death, activates the ERK and p38 signaling pathways, and exhibits excellent anti-HCC potential under suitable p-ERK inhibition conditions [ 42 , 43 ]. Zhang et al proposed that TQ can cooperate with TRAIL to induce apoptosis in HCC through the mediation of DNA damage [ 65 ].…”

Protective effects of butylated hydroxytoluene on the initiation of N-nitrosodiethylamine-induced hepatocellular carcinoma in albino rats

“…This injury initiates inflammation that leads to increased expression of mitogens, such as interleukin-6, that drive compensatory hepatocyte proliferation. 10,11 Butylated hydroxytoluene (BHT) is a highly lipophilic antioxidant that depletes peroxyl radicals and thus arrests oxidative processes. The antioxidant is used in cosmetic formulations and as a food additive and preservative.…”

“…9 DEN was reported to increase the malondialdehyde (MDA) levels because of increasing the ROS. 10 Inflammation is likely important for DEN-induced hepatocarcinogenesis. DEN is also a hepatotoxic substance that causes necrotic cell death.…”

Chemopreventive and therapeutic efficacy of thymoquinone on experimentally induced hamster buccal pouch carcinogenesis

“…Furthermore, several in vivo and in vitro studies have revealed the antineoplastic activities of TQ against a broad variety of solid tumors including head and neck cancers, with few side effects (30,(39)(40)(41)(42)(43) ). TQ is a pharmacologically active quinone, several studies were documented that TQ possess several medicinal properties including analgesic, anti-inflammatory, protective effect on lipid peroxidation and oxidative damage, anticonvulsant and also antioxidant effect (44)(45)(46)(47)(48)(49) . Growth inhibition of TQ is associated with inhibition of DNA synthesis and induction of cell cycle arrest (50)(51)(52)(53)(54)(55)(56) ).…”