Exploration of Medicine

Table 5. Number of animals (%) with histological cutaneous lesions in all experimental groups

Histological cutaneous lesions		G1 WT water	G2 HPV water	G3 WT 0.013 g/mL	G4 HPV 0.006 g/mL	G5 HPV 0.008 g/mL	G6 HPV 0.013 g/mL
Ear pavilion lesions
Dysplasia		0(0%)¹	5(100%)	0(0%)	5(100%)	4(80%)	4(80%)
Papilloma		0(0%)	3(50%)	0(0%)	2(40%)	0(0%)	1(20%)
Sebaceous hyperplasia		0(0%)	4(80%)	0(0%)	3(60%)	4(80%)	1(20%)
Inflammatory infiltrate		0(0%)¹	5(100%)	0(0%)²	5(100%)	5(100%)	5(100%)
Congestion		0(0%)¹	5(100%)	0(0%)²	0(0%)	0(0%)	1(20%)
Hyperplasia
Simple	Focal	0(0%)	0(0%)	0(0%)	0(0%)	0(0%)	1(20%)
Simple	Diffuse	0(0%)	0(0%)	0(0%)	0(0%)	1(20%)	(0%)
Papillary	Focal	0(0%)	0(0%)	0(0%)	0(0%)	0(0%)	0(0%)
Papillary	Diffuse	0(0%)	0(0%)	0(0%)	0(0%)	0(0%)	0(0%)
Papillomatosis	Focal	0(0%)	2(40%)	0(0%)	3(60%)	4(80%)	2(40%)
Papillomatosis	Diffuse	0(0%)	2(40%)	0(0%)	1(20%)	0(0%)	0(0%)
Carcinoma
Carcinoma in situ		0(0%)	1(20%)	0(0%)	0(0%)	0(0%)	0(0%)
Small invasive carcinoma		0(0%)	0(0%)	0(0%)	0(0%)	0(0%)	0(0%)
Invasive carcinoma		0(0%)	0(0%)	0(0%)	0(0%)	0(0%)	0(0%)
Chest skin lesions
Dysplasia		0(0%)¹	5(100%)	0(0%)	5(100%)	4(80%)	4(80%)
Sebaceous hyperplasia		0(0%)¹	5(100%)	0(0%)²	5(100%)	4(80%)	5(100%)
Inflammatory infiltrate		0(0%)	4(80%)	0(0%)	4(80%)	3(50%)	3(50%)
Simple	Simple	0(0%)	0(0%)	0(0%)	0(0%)	0(0%)	0(0%)
Simple	Diffuse	0(0%)	0(0%)	0(0%)	0(0%)	0(0%)	1(20%)
Papillary	Diffuse	0(0%)	0(0%)	0(0%)	0(0%)	0(0%)	0(0%)
Papillary	Focal	0(0%)	0(0%)	0(0%)	0(0%)	0(0%)	0(0%)
Papillomatosis	Diffuse	0(0%)	0(0%)	0(0%)	0(0%)	0(0%)	0(0%)
Papillomatosis	Focal	0(0%)	0(0%)	0(0%)	0(0%)	0(0%)	0(0%)
Papiloma	Inverted papiloma	0(0%)	0(0%)	0(0%)	0(0%)	0(0%)	0(0%)
Papiloma	Exophytic papiloma	0(0%)	2(40%)	0(0%)	1(20%)	1(20%)	1(20%)
Carcinoma	Carcinoma in situ	0(0%)	0(0%)	0(0%)	0(0%)	0(0%)	0(0%)
	Small invasive carcinoma	0(0%)	0(0%)	0(0%)	0(0%)	0(0%)	0(0%)
	Invasive carcinoma	0(0%)	0(0%)	0(0%)	0(0%)	0(0%)	0(0%)

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¹ Significantly different from the G2 (P < 0.05). ² Significantly different from the G6 (P < 0.05). G1 are wild-type (WT) mice that drink water; G2 are mice with human papillomavirus (HPV) that drank water; G3 are WT that drank daily an aqueous extract of Aloysia citrodora at a concentration of 0.013 g/mL; G4 are mice with HPV that drank daily an aqueous extract of A. citrodora at a concentration of 0.006 g/mL; G5 are mice with HPV that drank daily an aqueous extract of A. citrodora at a concentration of 0.008 g/mL; G6 are mice with HPV that drank daily an aqueous extract of A. citrodora at a concentration of 0.013 g/mL

Declarations

Author contributions

BMF: Conceptualization, Investigation, Writing—original draft. AIFR, MJP, MJN, IG, MMSMB, and CV: Writing—review & editing. HV, CVN, JS, MGS, LG, MID, LB, and LF: Investigation, Writing—review & editing. RM and RMGDC: Writing—review & editing, Supervision. PAO: Conceptualization, Writing—review & editing, Supervision.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

The experimental work was approved by the animal facility of the University of Trás-os-Montes e Alto Douro (UTAD) with the authorization of the Ethics Committee (approval no. 852-e-CITAB-2020_A_1-e- 122 CITAB-2021) and the Portuguese Veterinary Directorate (approval no. 014139).

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

The raw data supporting the conclusions of this manuscript will be made available by the authors, without undue reservation, to any qualified researcher.

Funding

Beatriz Medeiros-Fonseca has a Ph.D. grant with number [2020.07675.BD] (https://doi.org/10.54499/2020.07675.BD); Jéssica Silva has a Ph.D. grant with number [2020.07999.BD] (https://doi.org/10.54499/2020.07999.BD); Mónica G. Silva has a Ph.D. grant with number [UI/BD/151320/2021] (https://doi.org/10.54499/UI/BD/151320/2021) financed by FCT (Foundation for Science and Technology) through FSE (European Social Fund). This work is supported by National Funds by FCT-Portuguese under projects: CITAB [UID/04033/2020] (https://doi.org/10.54499/UIDB/04033/2020); CERNAS [UIDB/00681/2020] (https://doi.org/10.54499/UIDB/00681/2020); LEPABE [UIDB/00511/2020] (https://doi.org/10.54499/UIDB/00511/2020) and [UIDP/00511/2020] (https://doi.org/10.54499/UIDP/00511/2020); ALiCE [LA/P/0045/2020] (https://doi.org/10.54499/LA/P/0045/2020); CIMO [UIDB/00690/2020] (https://doi.org/10.54499/UIDB/00690/2020) and [UIDP/00690/2020] (https://doi.org/10.54499/UIDP/00690/2020); SusTEC, [LA/P/0007/2020] (https://doi.org/10.54499/LA/P/0007/2020); by national funds through the FCT/MCTES (PIDDAC). Furthermore, national funding by FCT/P.I., through the institutional scientific employment program contract for Lilian Barros, Maria I. Dias (https://doi.org/10.54499/CEECINST/00016/2018/CP1505/CT0004), Luís Félix (https://doi.org/10.54499/2021.00458.CEECIND/CP1690/CT0001) contract. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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