Antioxidant activity of fluoxetine: Studies in mice melanoma model

Abstract

In vivo effects of the antidepressant fluoxetine on spleen antioxidant status of C57BL/6 mice were studied using a melanoma experimental model. After a 14-day treatment with fluoxetine (10 mg kg À1 day À1 , i.p.), the endogenous antioxidant non-enzyme (glutathione) and enzyme (superoxide dismutase (SOD) and glutathione peroxidase (GPx)) defense systems in spleen of healthy animals were not changed; the lipid peroxidation (LP) was also unchanged. When B16F10 melanoma cells were introduced in C57BL/6 mice 2 h before fluoxetine treatment, a drug-protective effect against the melanoma-induced oxidative changes (increased LP and decreased total glutathione (GSH)-level, as well as antioxidant enzyme activities) in spleen was observed. Fluoxetine dose-dependently reduced the amounts of free oxygen radicals (hydroxyl and superoxide anion radicals), generated in chemical systems. Taken together, the present results suggest that fluoxetine, acting as antioxidant, prevents from melanoma-induced oxidative changes in mice spleen.

Serotonin and histamine mediate gastroprotective effect of fluoxetine against experimentally-induced ulcers in rats

“…Fluoxetine also significantly inhibited INDO-and ethanol-induced increases in MPO levels here; this outcome was in agreement with a previous study that demonstrated an inhibitory effect of fluoxetine on MPO levels in irritable bowel syndrome (Kato et al 1998). Fluoxetine also is known to inhibit the depletion in GSH to counter oxidative stresses produced during ulcer formation (Kirkova et al 2010). This antioxidant effect of fluoxetine might be related to the fact the drug causes increases in levels of serotonin (which itself imparts an anti-oxidant effect; Ham et al 1999).…”

Antidepressant fluoxetine and its potential against colon tumors

“…In these epithelial cells, it induces an increase in serotonin (5-HT) levels by blocking L-monoamine oxidase and serotonin reuptake transporters [41][42][43] . On the other hand, FLX has been shown to interfere with the OS machinery in experimental models and humans [44][45][46][47][48][49][50][51][52][53][54][55] . Treatment with FLX was found to reduce malondialdehyde (MDA) and carbonyl levels in stressed rats, whilst it enhanced superoxide dismutase (SOD), catalase, glutathione S-transferase, glutathione reductase and glutathione contents [45,46] .…”

“…We have already demonstrated that FLX treatment arrested colon tumor cells within the G0/G1 cell-cycle phase without inducing DNA damage [64] . Then, FLX was shown to reduce ROS generation, reversing the melanoma-induced tissue oxidation in mice [50] . In brain tissue of tumor-bearing mice, FLX treatment further reduced OS, enhancing the SOD activity [49] .…”

“…Comparing those reports that describe how FLX modulates tumor metabolism [49,50,[52][53][54][55] with others describing its activity against tumor growth [40,58,[87][88][89][90][91][92] , it becomes clear that FLX blocks tumor cell proliferation by impairing the malignant energy generation. The anti-tumor proliferative effects of FLX [40,56,92,93] have been related to different causes, such as delays in cell-cycle progression by inhibiting DNA synthesis and also to a possible binding directly to DNA via groove mode and high attraction force [58,[87][88][89][90]94] .…”

“…FLX treatment seems to block tumor growth by breaking the malignant metabolism down [49,[52][53][54][55] . While the pieces for this puzzle are slowly being pulled together, there are already several reports which have given the ground ideas for following investigations [38][39][40]49,50,[52][53][54][55][56]58,60,61,[64][65][66][67][87][88][89][90][91][92]95] . Besides the specific idea of FLX acting against the tumor metabolism, there is an open question regarding the effects of FLX treatment against the "reverse Warburg effect".…”