KRAS Mutation Reduces Thymoquinone Anticancer Effects on Viability of Cells and Apoptosis.

BACKGROUND: Cancer is a life-threatening condition with an economic burden on societies. Phytotherapy is rapidly taking place in cancer research to increase the success of treatment and quality of life. Thymoquinone (TQ) is the main active phenolic compound obtained from the essential oil of the Nigella sativa (black cumin) plant seed. For a long time, black cumin has been used traditionally for the remedy of different diseases because of its various biological effects. It has been shown that most of these effects of black cumin seeds are due to TQ. TQ became a popular research topic for phytotherapy studies for its potential therapeutic applications, and more research is going on to fully understand its mechanisms of action, safety, and efficacy in humans. KRAS is a gene that regulates cell division and growth. Monoallelic variants in KRAS result in uncontrollable cell division, leading to cancer development. Studies have shown that cancer cells with KRAS mutations are often resistant to certain types of chemotherapy and targeted therapies. OBJECTIVE: This study aimed to compare the effect of TQ on cancer cells with and without KRAS mutation to better understand the reason why TQ may have different anticancer effects in the different types of cancer cells. METHODS: TQ was investigated for its cytotoxic and apoptotic effects in laryngeal cancer cells (HEp-2) without KRAS mutation and compared to mutant KRAS-transfected larynx cancer cells and KRAS mutation-carrying lung cancer cells (A549). RESULTS: We showed that TQ has more cytotoxic and apoptotic effects on laryngeal cancer cells without KRAS mutation than in cells with mutation. CONCLUSION: KRAS mutations decrease the effect of TQ on cell viability and apoptosis, and further studies are needed to fully understand the relationship between KRAS mutations and thymoquinone effectiveness in cancer treatment.

Comparison of the efficacy of multiple antioxidant and hyperbaric oxygen treatments in the prevention of ischemia and necrosis of local random McFarlane skin flap.

OBJECTIVE: The aim of this study was to compare the efficacy of multiple antioxidant (Proxeed Plus (PP) with Carnitine, Selenium, Zinc, Coenzyme Q10, Vitamin C, Folic Acid, Vitamin B12) on local random skin flap healing with the hyperbaric oxygen (HBO) therapy. METHODS: Fourty rats were equally divided into five groups (Control, PP, HBO, HBO + PP, PP + HBO + PP). Local random McFarlane skin flap was applied to all rats. Following the applications, evaluations were made biochemical (TAS, TOS, OSI, IL-1ß, IL-6, TNF-α, TGF-ß, VEGF) and histopathological parameters. RESULTS: Necrosis percentage was found to be lower in the PP + HBO + PP group than all other groups whereas the necrosis percentages of PP and HBO groups were similar. Oxidative stress rates were significantly higher in the control group compared to the other groups whereas it was lower in the PP + HBO + PP group than all other groups. The inflammation parameters were the highest in the control group and the lowest in the PP + HBO + PP group. Growth factors were higher in the PP + HBO + PP group than all other groups. Epithelialization and wound healing were better in the HBO and PP groups than in the control group. The greatest healing, epithelialization and vascularization was seen in the PP + HBO + PP group. The histopathological findings in the PP + HBO + PP group were better in each inner region than in the other groups. CONCLUSION: Biochemical and histopathological parameters have shown that PP reduces ischemia and necrosis and increases oxygenation in flap healing by providing significant improvement thanks to the multiple molecular structures in its content.

Influence of Ginkgo Biloba extract (EGb 761) on expression of IL-1 Beta, IL-6, TNF-alfa, HSP-70, HSF-1 and COX-2 after noise exposure in the rat cochlea.

OBJECTIVE: The objective of this study was to investigate the influence of Ginkgo Biloba in early treatment of noise induced hearing loss on expression of IL-6, IL-1 Beta, TNF-alfa, HSP-70, HSF-1 and COX-2 in the rat cochlea. METHODS: Thirty two female rats were randomly divided into four groups (Acoustic Trauma, Ginkgo Biloba, Acoustic Trauma+Ginkgo Biloba, Non Treatment). Auditory brainstem response (ABR) was applied in all the groups. At the end of the study, IL-1Beta, IL-6, TNF-alpha, HSP-70, HSF-1 and COX-2 were studied in cochlear tissue with ELISA and Western blot analysis. RESULTS: There were significant increases in ABR values measured at days 1 and 7 compared to baseline values in Group 3. IL-1 Beta, IL-6 and TNF-alpha values were significantly higher in Group 1 than in the other groups. Whereas HSP-70 and HSF-1 values were found to be significantly lower in Group 1 compared to those in Group 2 and Group 3. COX-2 of Group 1 was significantly higher than the other groups. CONCLUSION: Ginkgo Biloba is helpful in the treatment of noise induced hearing loss and exerts its effect by inhibiting expression of IL-1 Beta, IL-6, TNF-alpha and COX-2 and increasing HSP-70 and HSF-1 values in rat cochlea.

Effectiveness of radiotherapy+ozone on tumoral tissue and survival in tongue cancer rat model.

OBJECTIVE: The objective of this study is to examine therapeutic effect of the combination of radiotherapy and ozone which features increasing of the destruction of cancer cells by increasing oxygen level of the body on advanced tongue cancer induced in rats. METHODS: A total of 36 female rats were included in this study as 4 groups. Group 1 (Cancer, n=8): 4NQO. Group 2 (Cancer+Radiotherapy, n=10): 4NQO+Radiotherapy. Group 3 (Cancer+Ozone+Radiotherapy, n=10): 4NQO+Ozone+Radiotherapy. Group 4 (Cancer+Ozone, n=10): 4NQO+Ozone. Group 5 (Control, n=8): Physiological saline solution. At the end of the week 20, rats in Groups 1 and 5 were sacrified. The rats in Groups 2,3 and 4 were waited until oral food intake was disrupted. The necessary applicatione were then carried out and survivals were evaluated. Each rat was sacrified after death. Tongues of the rats were excised, stained with hematoxylin & eosin and histopathologically evaluated. RESULTS: Histopathologic evaluation: The model that we applied was seen to achieve success in Group 1 in which 7 of the rats developed squamous cell carcinoma and one rat developed dysplasia at the end of the week 20. In Group 2 squamous cell cancer was seen in 6 and dysplasia in 4 rats. Six rats presented normal tongue tissues and 4 rats developed hyperplasia in Group 3. In Group 4; 3 rats had squamous cell cancer, 2 rats dysplasia, 3 rats hyperplasia and 2 rats had normal tissue. In Group 5, normal tongue tissues were observed in all rats. A significant histopathological improvement was observed in Group 3 compared to Group 2 (p<0.05). Histopathologic scorings were similar in Groups 3 and 5 (p>0.05). No statistically significant difference was found in histopathologic scorings between Group 1 and Group 2 (p>0.05). A significant improvement was observed in Group 4 compared to Group 1 (p<0.05). Group 3 showed a significant histologic improvement compared to Group 4 (p<0.05). Evaluation of survival: Survival times were found as 3.4±1.3 days, 76.4±14.9days and 76.4±14.9 days in the Groups 2, 3 and 4; respectively. Survival was significantly longer in Group 3 than in Groups 2 and 4 (p<0.05). Survival was significantly longer in Group 4 compared to Group 2 (p<0.05). CONCLUSION: In this study, demonstrated that radiotherapy plus ozone application both provided histopathological improvement and prolonged survival in advanced tongue cancer rat model.

Medical ozone therapy for the inner ear acoustic trauma.

OBJECTIVES: The goal of the study was to look at the potential protective effect of ozone therapy by studying its antioxidant and vasodilatation effects against hearing loss caused by acoustic trauma. METHODS: Thirty-two male Wistar Albino rats were divided into four groups of eight. The 1st group was exposed to acoustic trauma, the 2nd group was treated with ozone initially, and was exposed to acoustic trauma 24 h later, the 3rd group received ozone without trauma, while the 4th group was the control group. The 1st and 2nd groups were exposed to acoustic trauma with 105 dB SPL white band noise for 4h. DPOAE and ABR tests were conducted in all groups on the 1st, 5th, and 10th days after trauma. RESULTS: In the 1st group, the effects of acoustic trauma continued on days 1, 5 and 10. The 2nd group's DPOAE and ABR results on days 5 and 10 showed significant improvement at all frequencies compared to deterioration on day 1, and the readings were comparable to baseline measurements. CONCLUSION: Acoustic trauma is a pathology that is experienced frequently and leads to many problems in terms of health and cost. Ozone was demonstrated to be a reparative substance against acoustic trauma and, in addition, it can be supplied and applied easily.