Effects of thymoquinone on antioxidant enzyme activities, lipid peroxidation and DT‐diaphorase in different tissues of mice: a possible mechanism of action

Abstract

The present investigation focused, firstly, on the effects of oral administration of thymoquinone (TQ) on antioxidant enzyme activities, lipid peroxidation and DT-diaphorase activity in hepatic, cardiac and kidney tissues of normal mice. Superoxide dismutase (SOD; E.C:1.15.1.1), catalase (CAT; E.C:1.11.1.6), glutathione peroxidase (GSH-Px; E.C:1.11.1.9), glutathione-S-transferase (GST; E.C:2.5.1.18), and DT-diaphorase (E.C:1.6.99.2) enzyme activities in each tissue type were determined. Treatment of mice with the different doses of TQ (25, 50 and 100 mg kg(-1) day(-1) orally) for 5 successive days, produced significant reductions in hepatic SOD, CAT and GSH-Px activities. In addition cardiac SOD activity was markedly inhibited with the higher doses of TQ, (namely 50 and 100 mg kg(-1)). Moreover, TQ (100 mg kg(-1)) significantly reduced hepatic and cardiac lipid peroxidation as compared with the respective control group. Conversely, TQ (50,100 mg kg(-1)) and TQ (100 mg kg(-1)) enhanced cardiac and renal DT-diaphorase activity respectively. However, the selected doses of TQ neither produced any change in GST activity nor influenced reduced glutathione content in all tissues studied. TQ was tested, secondly, as a substrate for hepatic, cardiac and renal DT-diaphorase of normal mice in the presence of NADPH. Kinetic parameters for the reduction of TQ to dihydrothymoquinone (DHTQ) indicated that DT-diaphorase of different tissues can efficiently reduce TQ to DHTQ. K(m) and V(max) values revealed that hepatic DT-diaphorase exhibited the higher values, while the lower values were associated with renal DT-diaphorase. TQ and DHTQ were tested, thirdly, as specific scavengers for superoxide anion (generated biochemically) or as general scavengers for free radicals (generated photochemically). The results revealed that TQ and DHTQ acted not only as superoxide anion scavengers but also as general free radical scavengers. The IC(50) for TQ and DHTQ in biochemical and photochemical assays were in the nanomolar and micromolar range respectively. Our data may explain at least partly the reported beneficial in vivo protective effects of TQ through the combined antioxidant properties of TQ and its metabolite DHTQ.

Targeting Nuclear Factor-κB Activation Pathway by Thymoquinone: Role in Suppression of Antiapoptotic Gene Products and Enhancement of Apoptosis

“…Several components of black cumin have been identified, including thymoquione, thymol, thymohydroquinone, and dithymquinone (2,3). Thymoquinone (TQ), the most abundant component of black seed oil, has been reported to exhibit antioxidant (4)(5)(6), antiinflammatory, and chemopreventive (7-9) effects. For instance, TQ has been shown to suppress the proliferation of various tumor cells, including colorectal carcinoma, breast adenocarcinoma, osteosarcoma, ovarian carcinoma, myeloblastic leukemia, and pancreatic carcinoma (7,(10)(11)(12)(13)(14), although it is minimally toxic to normal cells (15).…”

The protective effect of thymoquinone over olanzapine-induced side effects in liver, and metabolic side effects

“…Nevertheless, TQ is known to reduce oxidative stress not only through the direct antioxidant effect but also indirectly. Previous studies reported that TQ acted as a strong reactive oxygen species (ROS) scavenger (45,46).…”

Effects of Nigella sativa and silver sulfadiazine on burn wound healing in rats

“…Thymoquinone is reported to prevent oxidative injury in various in vitro and in vivo studies in rats (Daba and Abdel-Rahman, 1998;Mansour et al, 2001;Yaman and Balikci, 2010). Thymoquinone has been suggested to act as an antioxidant and was reported to prevent membrane lipid peroxidation in tissues (Mansour et al, 2002). These effects seem to be related to inhibition of eicosanoid generation, namely thromboxane B2 and leucotrienes B4 (by inhibiting cyclooxygenase and 5-lipooxygenase, respectively), and membrane lipid peroxidation (Hosseinzadeh et al, 2007).…”