Prolonged ischemia due to ischemia-reperfusion (I/R) injury, lack of arterial or venous blood occurs when circulation is restored in organs and tissues. This has the greatest effect on oxygen-sensitive aerobic cells, which use mitochondrial oxidative phosphorylation as an energy source. For this reason, I/R damage is more likely to occur in organs and tissues that use aerobic metabolism (Mohamadian et al. 2022).
I/R injury is a common condition encountered during or after hypovolemic shock, chronic liver diseases, major tumor resections, surgical intervention to hepatic trauma, vascular reconstructions, and hepatic transplantation. Ischemia is the most common type of cell injury in clinical medicine. Therefore, it causes life-threatening problems in many tissues and organs, especially the brain, heart, kidneys and liver. Especially in hepatic ischemia models, many studies have been carried out and many agents have been used to minimize the resulting ischemic liver injury and subsequent reperfusion injury. However, since liver ischemia-reperfusion injury has not been clarified yet, it is important to understand the pathophysiology of liver I/R-related diseases in the clinic and to reveal different treatment modalities for these diseases (Mohamadian et al. 2022).
Thymoquinone (Tmq) is a monoterpene and the major compound of Nigella sativa seeds, a promising medicinal plant with many therapeutic effects (Oskouei et al. 2018). As a result of the investigations, 38.20% fat, 31.94% carbohydrates, 20.85% protein, 7.94% fiber and 4.64% water of the content of nigella sativa seeds (Oskouei et al. 2018). Tmq has also shown antioxidant effects. It inhibited inflammation in animal models and cell culture systems. Despite studies showing that Tmq is anticancer, antioxidant, antibacterial, antifungal, antiparasitic and antiasmatic, its mechanism of action has not yet been fully elucidated (Oskouei et al. 2018,Verma et al. 2022,Islam et al. 2021).
Studies have increased the possibility of TRP proteins being a new Ca+ 2permeable cation channel. TRP channels either act directly as Ca+ 2 entry channels in plasma membranes or they assist in the change in cytosolic free Ca+ 2channels that change the membrane potential, which is the driving force for the modulation of Ca+ 2 entry channels (Englisch et al. 2022). TRP channels play a role in many important cellular processes such as Ca+ 2-Mg+ 2 transmission, regulation of blood pressure, perception of taste, smell, sound, gene expression and secretion, apoptosis, and in many important mechanisms such as the commonly known secondary messenger mechanism, ion entry and exit play.
As a result of genetic studies, TRP channels were divided into 7 subfamilies according to their amino acid similarities. These are: TRPC (canonical), TRPM (melastatin), TRPV (vanilloid), TRPA (anycrine rich protein), TRPP (polycystin), TRPML (mucolipin), TRPN (nompc). The activation mechanisms of these channels and the organs in which they are located are different. For example, melastatin is mostly TRP found in brain and neuron cells (Huang et al. 2020). A total of 8 sub-members of the TRP Melastatin (TRPM) family, defined as TRPM1-TRPM8, have been reported (Huang et al. 2020,Cornillot et al. 2019). Sub-members of TRPM are classified under 4 groups according to their sequence similarities: TRPM1,3 TRPM2,8 TRPM4,5 and TRPM6,7. TRPM4,5 channels are not permeable to Ca + 2, while TRPM6 and 7 show high permeability to Ca + 2 and magnesium. Unlike TRPC and TRPV channels, TRPM channels do not contain ankyrin repeats (Huang et al. 2020,Cornillot et al. 2019). No activator has yet been demonstrated for the TRPM1 channel. It has been suggested that the TRPM1 channel is a constitutively active Ca + 2 entry channel (Huang et al. 2020,Cornillot et al. 2019). TRPM3 expression has been demonstrated in the kidney, brain, testis and spinal cord (Huang et al. 2020,Cornillot et al. 2019).
In our study, we planned to investigate the effects of thymoquinone on ischemia/reperfusion and TRPM 2,6,7,8 ion channels in liver tissues by creating an I/R model in the liver. Considering the important role of TRPM channels in ischemia and apoptosis, the clarification of this issue and therefore the relationship between the expression of TRPM 2,6,7,8 channels and thymoquinone will allow to evaluate its potential in the diagnosis and treatment of both ischemia and apoptosis and liver-related diseases. Considering the important role of TRPM channels in ischemia and apoptosis, with the presented study; It is aimed to contribute to the evaluation of both the relationship of TRPM channel expressions with Tmq and the potential of Tmq in the diagnosis and treatment of ischemia, apoptosis and liver-related diseases.