Genista cephalantha Spach. protects against acetaminophen-induced liver failure via preserving the glutathione redox system, reducing inflammatory response, and inhibiting hepatocyte death in rats

Objective(s): The current study was conducted to assess the protective mechanisms of n-BuOH fraction from the aerial part of Genista cephontala (BEGC) on APAP-induced liver injury compared to necrostatine-۱ (Nec-۱).Materials and Methods: A model of APAP-induced hepatotoxicity was created in male rats by injecting a single dose; ۱۰۰۰ mg/kg APAP, the protective effect was performed with (۲۰۰ mg/kg; ۱۰ days) BEGC compared to Nec-۱, (۱.۸ mg/kg).Results: BEGC or NeC-۱ pretreatment significantly abolished impaired effects in APAP-rats, by decreasing the generation of TBARS and ROS in mitochondrial and cytosolic fractions and maintaining liver function activities. A marked response was observed in the levels of both GSH and GSH-system enzymes in liver homogenates and mitochondrial fractions to BEGC. BEGC/ Nec-۱ successfully regulated the inflammatory mediators (IL-β, TNF-α, HMGB۱, and acHMGB۱) and MPO levels. During APAP treatment, no caspase-۳ or -۸ activity was detected, and the level of fk۱۸; M۳۰ was higher than the levels of cck۱۸; M۶۵. Moreover, RIPK۳ and MLKL levels were increased in the APAP group. These results suggested that necroptosis predominates during the APAP liver injury model. Interestingly, these necroptotic factors were significantly down-regulated by BEGC treatment. Both biochemical and histopathological findings were consistent with each other.Conclusion: From all these findings, the hepatoprotective effect of BEGC could be due to the abundance of polyphenols identified by LC-MS/MS analysis, as well as the synergistic interactions of all contents.

Keywords:

Acetaminophen , Cell death , Hepatoprotection Inflammation , LC-MS/MS , Necroptosis , Necrostatin-۱ , Oxidative stress