Review for 10.1186/1471-230X-9-36 (2009)

Reviewer's report
Title:Antiulcer activity of fluvoxamine in rats and its effect on oxidant and
antioxidant parameters in stomach tissue
Version: 2Date:21 January 2009
Reviewer: Predrag Sikiric
Reviewer's report:
This study aimed to investigate the antiulcer effects of fluvoxamine and to
determine its relationship with antioxidant mechanisms. This idea may be in
generally interesting, particularly considering the most recent data presented by
the same group (see ref. 20 Bilici M, Ozturk C, Dursun H, Albayrak F, Saglam
MB, Uyanik A, Gulaboglu M, Tekin SB: Protective effect of mirtazapine on
indomethacin-induced ulcer in rats and its relationship with oxidant and
antioxidant parameters. Dig Dis Sci. (in press).) However, this reviewer still
objects the elaboration. The following arguments have been provided:
Abstract
Abstract. This study aimed to investigate the antiulcer effects of fluvoxamine and
to determine its relationship with antioxidant mechanisms.
Comment: If authors consider that this may be important – they should provide
some notes in Background section about the importance of antidepressant (or
fluvoxamine)-antioxidant effect relation, or at least, about antiulcer-antioxidant
effect. This could be done presenting their recent work (i.e., Bilici M, Ozturk C,
Dursun H, Albayrak F, Saglam MB, Uyanik A, Gulaboglu M, Tekin SB: Protective
effect of mirtazapine on indomethacin-induced ulcer in rats and its relationship
with oxidant and antioxidant parameters. Dig Dis Sci. (in press).)
Abstract. 24 h fasted rat groups received fluvoxamine (25, 50, 100 and 200
mg/kg) ranitidine and distilled water. Indomethacin (25 mg/kg) administered to all
rats as ulcerative agent.
Comment: This is the crucial statement, and needs to be carefully specified. No
indication about the ranitidine dose, no indication about the way of application!
Abstract. Conclusion: We conclude that fluvoxamine has both antidepressant and
antiulcer effects. Activation of antioxidant mechanisms and inhibition of some
toxic oxidant mechanisms are involved in antiulcer effect mechanism of
fluvoxamine. This new indication of fluvoxamine will make it the first-choice drug
in depressive patients with gastric ulcers.
Comment: The authors did examine the potential antiulcer effect of fluvoxamine.
So, they could conclude that it has an antiulcer effect.
Since the experiments showing that within the same dose range fluvoxamine
have also an antidepressant effect are lacking in this study, the conclusion
should be limited to the antiulcer effect only. Besides, since authors claimed in
the Background “Antidepressant drugs have been used for several
non-psychiatric indications. A lot of antidepressant drugs have been shown to
produce antiulcer activity in various
models of experimental ulcer“. the conclusion about the fluvoxamine
as the first-choice drug in depressive patients with gastric ulcer seems to be not
firmly based.
In conclusion, Abstract lacks the important points, and it has to completely
rewritten and corrected.
Introduction
The essential claim „Antidepressant drugs have been found to be effective in
ulcer treatment [8, 9].“ seems to be poorly supported, since the paper (cited as 8)
Itoh M, Guth PH: Role of oxygen-derived free radicals in hemorrhagic shock
induced gastric lesions in the rat.
Gastroenterology. 1985;88:1162-7. has nothing with antidepressant agents.
This reviewer strongly believes that authors should focus a significant part of
Introduction to demonstrate that antiulcer effect is an effect common for
antidepressants, and if so, why fluvoxamine is worthy of special investigation.
This should be done particularly considering that in addition to general
differences between the various generations of antidepressants, every one of
antidepressants may have its special effects, and therefore, a generalization
should be carefully substantiated. Besides, the final claim in Introduction “Also,
the importance of increasing antioxidant parameters and decreasing oxidant
parameters in the antiulcer effect mechanism of mirtazapin, an antidepressant
drug, has been reported [20]. To date, however, there is no information
investigates the antiulcer activity of fluvoxamine in an indomethacin induced ulcer
model on rats, and evaluates its effects on oxidant and antioxidant parameters in
rat stomach tissue.“ may be questionable considering different mechanisms
involved in the effects of mirtazepin and fluvoxamine.
In conclusion, although the idea may be very interesting, it seems that
Introduction in the present form does not provide a suitable background, and
therefore, it has to be completely rewritten. Specifically, all of the claims should
be substantiated by the suitable (and correct) citations.
Results
In generally, it seems that the repetition of the data in the text is not needed
presenting that all these data are shown in Tables.
Discussion
This reviewer strongly objects the statement: „But aspirin, which inhibits
sito-protective PGE2, was shown to not produce gastric damage and even
prevent indomethacin-induced ulcers when administered intraperitonelally [31].“
Namely, aspirin is commonly known to produce ulcer. The authors are kindly
addressed to Robert, Gastroenterology 1979, where aspirin (producing small
lesions) is capable to prevent stronger lesions that would be otherwise induced
by indomethacin, a stronger ulcerogen application.
The spelling should be “cyto-protective”.
In generally, this reviewer appreciates the efforts done by the authors to
emphasize the possible influence of fluvoxamine on antioxidant mechanisms.
However, the authors completely disregarded that fluvoxamine, a structural
derivative of fluoxetine, is one of the serotonin-specific reuptake inhibitors, and
therefore, presenting the role of serotonin (particularly in the CNS but also in the
stomach), they should provide the arguments why this effect should be related
only to the antioxidant effect. Besides, in the case of NO, it would be nice to
provide the arguments that this effect could be mitigated by L-NAME application
as well as potentiated by L-arginine application. Finally, considering the final
conclusion “In conclusion, we can say that fluvoxamine has both antidepressant
and antiulcer effects. “ (antidepressant and antiulcer effect!) see our previous
comments. Once again, the specific conclusion should be substantiated by the
findings presented in the study while the demonstration of the antidepressant
effect of fluvoxamine within the doses range used to demonstrate its antiulcer
effect is lacking. Besides, to demonstrate the special antiulcer effect of
fluvoxamine (the authors claimed that it has to be the first-choice drug) it would
be worthy to include more ulcer models than only one (indomethacin) ulcer.
Finally, the very interesting effects were demonstrated for ranitidine as well.
Therefore, this merits some comments as well.
In conclusion, although the Discussion is more than interesting, it seems that it
has to be rewritten and corrected.
Level of interest: An article of outstanding merit and interest in its field
Declaration of competing interests:
To all these questions I declare that I have no competing interests' below.