The evaluation of the protective effect of nigella sativa on the doxorubicin induced chemo-brain in the rats

Introduction: Breast cancer is the most common cancer and the most common reason of cancer related mortality in women. Recently, the decrease in the mortality has been seen along with the early diagnosis and treatment. But, most of the chemotherapeudic drugs used in the treatment of breast cancer have severe cytotoxic side effects and have low selectivity to cancer cells. Doxorubicin used in the treatment of breast cancer for a long time, has also severe side effects. In these side effects, chemo-brain is frequently encountered in clinical practice. Chemo-brain manifests itself with the impairment of cognitive functions in the long term. In experimental studies, several molecules had been investigated their effects on the chemo-brain. Favourable effects of Nigella sativa on many diseases, that has an antioxidant property, have been revealed with the various studies. There is no study showing the efficacy of Nigella sativa, with proven effects on some diseases, on the doxorubicin induced chemo-brain. Objective: In our study we planned to research the efficacy of Nigella sativa on the doxorubicin induced chemo-brain in a murine model. Material and method: The study included 24 female Wistar Albino rats, randomly divided into control group, doxorubicin group and doxorubicin+Nigella sativa group, each containing eight rats. Chemo-brain induction was performed with doxorubicin. Doxorubicin was given intraperitoneally at the dose of 5 miligram/kilogram/day at the 1. 8. and 15. days, with totally three times during 28 days. Nigella sativa extraction was performed with ethanol methods. Nigella sativa extract was given with gavage everyday at the dose of 400 miligram/kilogram/day during 28 days. The severity of chemo-brain was assessed with open-field test at 29. day in terms of anxiety and passive-avoidence test at 30. and 31. days in terms of cognitive functions. In the open-field test, total distance travelled, mobil and immobile time, mobile and immobile episodes, mean and maximum speeds, crossed lines, number of enterance into center and border zones, total, mobile and immobile time spent, mean speeds and distance travelled in center and border zones were recorded. In the passive avoidance test, electrical stimuli was given to rats in the dark chamber at the first day. Latency time to first enterance into the dark chamber were recorded at the second day. The rats that did not enter the dark chamber assumed that it has learned. The rates of learning were recorded. The weight of the rats were evaluated at 1. 2. 3. 4. and 5. weeks. Data were statistically compared. The difference was assumed significant when p-value was <0.05. Results: Mobile, immobile, active and inactive episodes were found to be significantly lower in doxorubicin group compared with the control group (p˂0,05). The number of enterance into the center and border zones and the distance travelled in the center zone were found to be significantly higher in doxorubicin group compared with the control group (p˂0,05). There was no significant difference between the two groups in terms of the time spent in border and center zones and mobile time spent in center zone although the time spent in border zone was lower, total and mobile time spent in center zone were higher in doxorubicin group compared with control group (p˃0,05). Active and inactive episodes and the time spent in border zone were found to be significantly higher in doxorubicin+Nigella sativa group compared with doxorubicin group (p˂0,05). The number of enterance into the center and border zones, the distance travelled in the center zone, total and mobile time spent in center zone were found to be significantly lower in doxorubicin+Nigella sativa group compared with doxorubicin group (p˂0,05). There was no significant difference between the two groups in terms of the number of mobile and immobile episodes although they were higher in doxorubicin+Nigella sativa group compared with doxorubicin group (p˃0,05). There was no significant difference between doxorubicin+Nigella sativa and control groups in terms of all the parameters (p˃0,05). In all the groups, the time spent and total distance travelled in border zone were significantly higher than that in center zone (p˂0,05). Mean speed in center zone was significantly higher than that in border zone (p˂0,05). The number of active episodes was significantly higher than the number of inactive episodes (p˂0.05). Mobile time spent was significantly higher than immobile time spent in center zone (p˂0,05). There was no significant difference between all the groups in terms of total mobile and immobile time spent, mobile and immobile time spent in border zone, immobile time spent in center zone, total distance and head-distance travelled, mean and maximum speed, the number of line crossing, mean speed in center and border zones and distance travelled in border zone (p˃0,05). Mobile and immobile time spent, the number of mobile and immobile episodes, mobile and immobile time spent in border zone, the number of enterence into the center and border zones were statistically similar in all the groups (p˃0,05). Discussion: Doxorubicin decreases anxiety-like behaviours compared with normal animal. That doxorubicin decreases the anxiety lower than certain level naturally required for survival instinct, it give rise to thought that doxorubicin has a harmful effects on the central mechanisms regulating anxiety. Nigella sativa keeps up the anxiety with the intended level for surviving by the way of prevention of this damage. Cognitive impairment did not develop with short-term doxorubicin induction. For this, long-term induction with the doxorubicin may be needed. Because of that, it was concluded that there is a necessity of long-term study for evaluation of the effects of Nigella sativa on the cognitive functions. Conclusion: Nigella sativa has a protective effect on the emotional behavioural alterations caused by doxorubicin, but there is needed the experimental study that doxorubicin is used long-term and rats are followed in that period for revealing of the effect of Nigella sativa on the cognitive functions. Keywords: Chemobrain, Doxorubicin, Nigella sativa, Rat