Mechanistic Insights on the In Vitro Antibacterial Activity and In Vivo Hepatoprotective Effects of Salvinia auriculata Aubl against Methotrexate-Induced Liver Injury.
Nashwah G M AttallahFatma Alzahraa MokhtarEngy ElekhnawySelim Z HeneidyEman Abdelnaby AhmedSameh MagdeldinWalaa A NegmAya Hassan El-KademPublished in: Pharmaceuticals (Basel, Switzerland) (2022)
Methotrexate (MTX) is widely used in the treatment of numerous malignancies; however, its use is associated with marked hepatotoxicity. Herein, we assessed the possible hepatoprotective effects of Salvinia auriculata methanol extract (SAME) against MTX-induced hepatotoxicity and elucidated the possible fundamental mechanisms that mediated such protective effects for the first time. Forty mice were randomly allocated into five groups (eight/group). Control saline, MTX, and MTX groups were pre-treated with SAME 10, 20, and 30 mg/kg. The results revealed that MTX caused a considerable increase in blood transaminase and lactate dehydrogenase levels, oxidative stress, significant activation of the Nod-like receptor-3 (NLPR3)/caspase-1 inflammasome axis, and its downstream inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18). MTX also down-regulated nuclear factor erythroid 2-related factor 2 (Nrf2) expression. Additionally, it increased the immunostaining of nuclear factor kappa-B (NF-κB) and downstream inflammatory mediators. Furthermore, the hepatic cellular apoptosis was dramatically up-regulated in the MTX group. On the contrary, prior treatment with SAME significantly improved biochemical, histopathological, immunohistochemical alterations caused by MTX in a dose-dependent manner. The antibacterial activity of SAME has also been investigated against Acinetobacter baumannii clinical isolates. LC-ESI-MS/MS contributed to the authentication of the studied plant and identified 24 active constituents that can be accountable for the SAME-exhibited effects. Thus, our findings reveal new evidence of the hepatoprotective and antibacterial properties of SAME that need further future investigation.
Keyphrases
- nuclear factor
- oxidative stress
- toll like receptor
- ms ms
- acinetobacter baumannii
- diabetic rats
- drug resistant
- induced apoptosis
- cell death
- dna damage
- drug induced
- high dose
- pseudomonas aeruginosa
- ischemia reperfusion injury
- silver nanoparticles
- transcription factor
- mass spectrometry
- adipose tissue
- cell proliferation
- inflammatory response
- gene expression
- dna methylation
- type diabetes
- metabolic syndrome
- high resolution
- long non coding rna
- liquid chromatography
- pi k akt
- heat shock protein
- endothelial cells