Effects of Mexican Ganoderma lucidum extracts on liver, kidney, and the gut microbiota of Wistar rats: A repeated dose oral toxicity study.
Well-characterized and standardized extracts of a Mexican genotype of Ganoderma lucidum (Gl), a medicinal mushroom, cultivated on oak sawdust (Gl-1) or oak sawdust plus acetylsalicylic acid (Gl-2, ASA), have been shown to exert antioxidant, hypocholesterolemic, anti-inflammatory, prebiotic, and anti...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2023-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0283605 |
| _version_ | 1797843208262123520 |
|---|---|
| author | María E Meneses Daniel Martínez-Carrera Laura González-Ibáñez Nimbe Torres Mónica Sánchez-Tapia Claudia C Márquez-Mota Gilmar Rendón Vladimir Mitzi Alfredo Morales Isaac Tello-Salgado Armando R Tovar |
| author_facet | María E Meneses Daniel Martínez-Carrera Laura González-Ibáñez Nimbe Torres Mónica Sánchez-Tapia Claudia C Márquez-Mota Gilmar Rendón Vladimir Mitzi Alfredo Morales Isaac Tello-Salgado Armando R Tovar |
| author_sort | María E Meneses |
| collection | DOAJ |
| description | Well-characterized and standardized extracts of a Mexican genotype of Ganoderma lucidum (Gl), a medicinal mushroom, cultivated on oak sawdust (Gl-1) or oak sawdust plus acetylsalicylic acid (Gl-2, ASA), have been shown to exert antioxidant, hypocholesterolemic, anti-inflammatory, prebiotic, and anticancer properties. However, toxicity analyses still need to be carried out. Different doses of these Gl-1 or Gl-2 extracts were administered to Wistar rats for 14 days in a repeated dose oral toxicity study. We assessed the external clinical signs, biochemical parameters, liver and kidney tissues, injury and inflammation biomarkers, gene expression, inflammatory responses, proinflammatory mediators, and gut microbiota. Gl extracts had no significant adverse, toxic or harmful effects on male and female rats compared to the control groups. No injury or dysfunction were recorded in the kidney or liver, as there were no significant abnormal variations in organ weight, tissue histopathology, serum biochemical parameters (C-reactive protein, creatinine, urea, glucose, ALT and AST transaminases, TC, LDL-c, TG, HDL-c), urinary parameters (creatinine, urea nitrogen, albumin, the albumin-to-creatinine ratio, glucose), injury and inflammatory biomarkers (KIM-1/TIM-1, TLR4, and NF-кB protein expression; IL-1β, TNF-α and IL-6 gene expression), or the expression of genes linked to cholesterol metabolism (HMG-CoA, Srebp2, Ldlr). Gl-1 and Gl-2 extracts showed prebiotic effects on the gut microbiota of male and female Wistar rats. Bacterial diversity and relative bacterial abundance (BRA) increased, positively modulating the Firmicutes/Bacteroidetes ratio. The ASA (10 mM) added to the substrate used for mushroom cultivation changed properties and effects of the Gl-2 extract on Wistar rats. The no-observed-adverse-effect-level (NOAEL) was 1000 mg/kg body weight/day of Gl-1 or Gl-2 extracts. Clinical trials are recommended for further exploring the potential therapeutic applications of studied extracts. |
| first_indexed | 2024-04-09T17:01:10Z |
| format | Article |
| id | doaj.art-dd1710f06ef64545b86399aeb0cd0016 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-09T17:01:10Z |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-dd1710f06ef64545b86399aeb0cd00162023-04-21T05:32:26ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-01184e028360510.1371/journal.pone.0283605Effects of Mexican Ganoderma lucidum extracts on liver, kidney, and the gut microbiota of Wistar rats: A repeated dose oral toxicity study.María E MenesesDaniel Martínez-CarreraLaura González-IbáñezNimbe TorresMónica Sánchez-TapiaClaudia C Márquez-MotaGilmar RendónVladimir MitziAlfredo MoralesIsaac Tello-SalgadoArmando R TovarWell-characterized and standardized extracts of a Mexican genotype of Ganoderma lucidum (Gl), a medicinal mushroom, cultivated on oak sawdust (Gl-1) or oak sawdust plus acetylsalicylic acid (Gl-2, ASA), have been shown to exert antioxidant, hypocholesterolemic, anti-inflammatory, prebiotic, and anticancer properties. However, toxicity analyses still need to be carried out. Different doses of these Gl-1 or Gl-2 extracts were administered to Wistar rats for 14 days in a repeated dose oral toxicity study. We assessed the external clinical signs, biochemical parameters, liver and kidney tissues, injury and inflammation biomarkers, gene expression, inflammatory responses, proinflammatory mediators, and gut microbiota. Gl extracts had no significant adverse, toxic or harmful effects on male and female rats compared to the control groups. No injury or dysfunction were recorded in the kidney or liver, as there were no significant abnormal variations in organ weight, tissue histopathology, serum biochemical parameters (C-reactive protein, creatinine, urea, glucose, ALT and AST transaminases, TC, LDL-c, TG, HDL-c), urinary parameters (creatinine, urea nitrogen, albumin, the albumin-to-creatinine ratio, glucose), injury and inflammatory biomarkers (KIM-1/TIM-1, TLR4, and NF-кB protein expression; IL-1β, TNF-α and IL-6 gene expression), or the expression of genes linked to cholesterol metabolism (HMG-CoA, Srebp2, Ldlr). Gl-1 and Gl-2 extracts showed prebiotic effects on the gut microbiota of male and female Wistar rats. Bacterial diversity and relative bacterial abundance (BRA) increased, positively modulating the Firmicutes/Bacteroidetes ratio. The ASA (10 mM) added to the substrate used for mushroom cultivation changed properties and effects of the Gl-2 extract on Wistar rats. The no-observed-adverse-effect-level (NOAEL) was 1000 mg/kg body weight/day of Gl-1 or Gl-2 extracts. Clinical trials are recommended for further exploring the potential therapeutic applications of studied extracts.https://doi.org/10.1371/journal.pone.0283605 |
| spellingShingle | María E Meneses Daniel Martínez-Carrera Laura González-Ibáñez Nimbe Torres Mónica Sánchez-Tapia Claudia C Márquez-Mota Gilmar Rendón Vladimir Mitzi Alfredo Morales Isaac Tello-Salgado Armando R Tovar Effects of Mexican Ganoderma lucidum extracts on liver, kidney, and the gut microbiota of Wistar rats: A repeated dose oral toxicity study. PLoS ONE |
| title | Effects of Mexican Ganoderma lucidum extracts on liver, kidney, and the gut microbiota of Wistar rats: A repeated dose oral toxicity study. |
| title_full | Effects of Mexican Ganoderma lucidum extracts on liver, kidney, and the gut microbiota of Wistar rats: A repeated dose oral toxicity study. |
| title_fullStr | Effects of Mexican Ganoderma lucidum extracts on liver, kidney, and the gut microbiota of Wistar rats: A repeated dose oral toxicity study. |
| title_full_unstemmed | Effects of Mexican Ganoderma lucidum extracts on liver, kidney, and the gut microbiota of Wistar rats: A repeated dose oral toxicity study. |
| title_short | Effects of Mexican Ganoderma lucidum extracts on liver, kidney, and the gut microbiota of Wistar rats: A repeated dose oral toxicity study. |
| title_sort | effects of mexican ganoderma lucidum extracts on liver kidney and the gut microbiota of wistar rats a repeated dose oral toxicity study |
| url | https://doi.org/10.1371/journal.pone.0283605 |
| work_keys_str_mv | AT mariaemeneses effectsofmexicanganodermalucidumextractsonliverkidneyandthegutmicrobiotaofwistarratsarepeateddoseoraltoxicitystudy AT danielmartinezcarrera effectsofmexicanganodermalucidumextractsonliverkidneyandthegutmicrobiotaofwistarratsarepeateddoseoraltoxicitystudy AT lauragonzalezibanez effectsofmexicanganodermalucidumextractsonliverkidneyandthegutmicrobiotaofwistarratsarepeateddoseoraltoxicitystudy AT nimbetorres effectsofmexicanganodermalucidumextractsonliverkidneyandthegutmicrobiotaofwistarratsarepeateddoseoraltoxicitystudy AT monicasancheztapia effectsofmexicanganodermalucidumextractsonliverkidneyandthegutmicrobiotaofwistarratsarepeateddoseoraltoxicitystudy AT claudiacmarquezmota effectsofmexicanganodermalucidumextractsonliverkidneyandthegutmicrobiotaofwistarratsarepeateddoseoraltoxicitystudy AT gilmarrendon effectsofmexicanganodermalucidumextractsonliverkidneyandthegutmicrobiotaofwistarratsarepeateddoseoraltoxicitystudy AT vladimirmitzi effectsofmexicanganodermalucidumextractsonliverkidneyandthegutmicrobiotaofwistarratsarepeateddoseoraltoxicitystudy AT alfredomorales effectsofmexicanganodermalucidumextractsonliverkidneyandthegutmicrobiotaofwistarratsarepeateddoseoraltoxicitystudy AT isaactellosalgado effectsofmexicanganodermalucidumextractsonliverkidneyandthegutmicrobiotaofwistarratsarepeateddoseoraltoxicitystudy AT armandortovar effectsofmexicanganodermalucidumextractsonliverkidneyandthegutmicrobiotaofwistarratsarepeateddoseoraltoxicitystudy |