PONE-D-22-30736Cunaniol: Behavioral, electrophysiological changes in Colossoma macropomum (Tambaqui)PLOS ONE

Dear Dr. Muto,

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Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: N/A

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Dear authors,

The study of Cunaniol-induced seizures in fish is very interesting and holds great potential. I hope that the feedback provided below will enhance the quality of the manuscript and increase its chances of acceptance and publication.

Kind regards.

Comments:

Page 1, lines 1-2: “Cunaniol: Behavioral, electrophysiological changes in Colossoma macropomum (Tambaqui)”. I recommend modifying the title of the manuscript to make it clearer.

Page 4, lines 93-94: “In relation to its chemical composition, cunaniol C14H14O2 has as nomenclature: (2R, 3S) -2 - [(Z) -non-1-en-3,5,7-triinyl] oxan-3-ol] following IUPAC rules”. Please enclose the chemical formula of cunaniol in parentheses, and also provide the meaning of the IUPAC acronym (International Union of Pure and Applied Chemistry).

Page 5, lines 103-104: “… potent action of this extract as a chemoconvulsant agent with changes in brain oscillations in Beta (12 to 28 Hz)”. To make the text clearer, I suggest using ‘changes in Beta brain oscillations (12 to 28 Hz)’.

Please correct and standardize the bibliographic references in the text to conform to the journal guidelines for citations (https://journals.plos.org/plosone/s/submission-guidelines#loc-references). For example, in the body of the text, you can cite ‘Costa and colleagues (2006) [corresponding reference number here]…’ (page 5, line 105).

Page 5, line 116: “… to analyze behavioral, and electrophysiological responses in…”. The comma is not necessary.

Page 7, line 166-169: “… and the same tissues were collected for oxidative stress evaluation; (…) at the end of this experiment, muscle, brain and heart tissues were collected to evaluate oxidative stress after contact…”. The results of the experiments measuring oxidative stress are not included in the manuscript. Therefore, I recommend either removing this information from the text or providing an explanation for its intended publication in a future work.

Pages 7 and 8, lines 161-180: Please improve the presentation of the groups treated in each experiment.

Page 11, lines 255-261: Please clearly indicate the statistical analysis used in each performed experiment.

Page 12, line 275: Table 1 is redundant as its information is already detailed in the text.

Page 12, line 277: Replace “electroencephalographic record amplitude” with ‘EEG amplitude’.

Figure 1: In Figures 1A and 1B, there is a correlation between the left and right images (1A = 300 s; 1B = 600 s), hence they should be aligned closely. The images in the center are cutouts of the original tracing of the electrophysiological record. Therefore, it is recommended to place them to the right of the original image, which should have the selected sections clearly marked. In my opinion, Figures 1A and 1B should be arranged in a vertical orientation, with each figure having two columns (similar to Figure 3B), to enhance their visual appeal and make interpretation of the images easier.

Page 14, line 317: “The normal ECG of C. macropomum is shown in Figures 317 6 A and B, ...”. I believe that the normal ECG is displayed in Figure 5.

Page 15, line 355: “… induced seizure outbreaks, changes in the EEG recordings observed in Figure 8 C were…”. The correct figure is 7C.

Figures 3 and 7: I suggest redoing the figures based on the comment about figure 1.

Page 18, line 425: I suggest concluding the discussion with questions and perspectives on the use of this substance in future works.

Finally, I suggest a thorough review of the text to correct errors and improve coherence.

Reviewer #2: The authors should better describe the toxic substance Cunaniol in the introduction.

The authors do not make it clear, whether the effect of cunaniol on bradycardia is direct or indirect?

Cunaniol is an alcohol and could be blocking ionotropic glutamate receptors , why the authors did not test this possibility?

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Reviewer #1: No

Reviewer #2: Yes: José Luiz Martins do nascimento

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Behavioral, electrocorticographic and electrocardiologic changes in Colossoma macropomum (Tambaqui) in the effect of cunaniol

PONE-D-22-30736R1

Dear Dr. Muto,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Pan Li, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: (No Response)

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: When resubmitting the manuscript, the authors

included a listing the points

raised by the reviewe, and including both a final

version of the paper and a highlighted version showing

where the changes have been made.

The authors have reviewed the manuscript extensively and is now appropriate to be published.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: Yes: José Luiz Martins do Nascimento

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