Mechanistic Insights on the In Vitro Antibacterial Activity and In Vivo Hepatoprotective Effects of Salvinia auriculata Aubl against Methotrexate-Induced Liver Injury

Abstract

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.

Investigation of bioactive components responsible for the antibacterial and anti-biofilm activities of Caroxylon volkensii by LC-QTOF-MS/MS analysis and molecular docking

“…Furthermore, the mice were housed in a controlled environment with a temperature set at 25 °C and subjected to a 12 hour light and dark cycle. 27 Following a 7 day acclimation period for the mice, the in vivo experiment was conducted in accordance with the established guidelines for laboratory animal care and services. The study received ethical approval with the designated number TP/RE/06-22P-014 from the Research Ethical Committee of the Faculty of Pharmacy at Tanta University, Egypt.…”

Dietary Importance of Lycopene Against Carbon Tetrachloride Induced Hepatotoxicity in Rats

“…Hepatic dysfunction is due to many problems such as exposure to frequent doses of medications, drug therapy and compounds in environment caused toxicity (Attallah et al, 2022). Liver injury may occur due to many diseases such as non-insulin dependent diabetes and renal disease (Byrne and Targer, 2022).…”

N-Acetyl cysteine alleviates carbon-tetrachloride induced acute liver injury in rats

“…Liver is one of the dynamic organs that has a crucial role in macromolecules metabolism, bile acid biosynthesis and detoxification process of circulating agents (Zheng et al, 2022). Liver injury is attributed to multiple issues as subjection to repeated doses of drugs, medicine-based treatment, and toxic substances in the surrounding environment (Attallah et al, 2022). It also occurs as consequence of some diseases like non-insulin dependent diabetes mellitus, chronic kidney, and heart failure (Byrne and Targher, 2022).…”