Perspective for breaching the positive feedback loop between necroptosis and pyroptosis with spirulina in alcoholic liver injury induced in mice

The functional nutraceutical Spirulina (SP) was evaluated against alcohol intoxication in mice livers, concurrently striving to elucidate its protective mechanisms in cellular death pathways: necroptosis and pyroptosis. Ethanol (ET) intoxication was induced via intake of 5% ethanol in drinking water for 10 days, succeeded by a substantial dose of 50% ethanol (4 g/kg, i.p.) on day 11. SP (250 and 300 mg/kg, p.o.) were administered to the ET-intoxicated mice one hour prior to ethanol consumption for 11 days. The two submaximal doses effectively modulated the ET-instigated hepatic abnormalities. Both doses restored the disrupted hepatic function and architecture. SP mitigated serum liver biomarkers: ALT, AST and ALP, in addition to improving survival. SP substantially modified hepatic oxidative stress by inhibiting the lipid peroxidation product MDA and elevating the antioxidant levels of SOD and GSH. Meanwhile, SP counteracted the ET-induced elevated levels of hepatic TNF-α, the necroptosis-related molecular signals; RIPK1/RIPK3/MLKL and the pyroptosis biomarkers: NLRP3/caspase-1/IL-1β. However, no extra benefit was detected with the higher dose. These findings robustly imply the hepatoprotective properties of Spirulina in alcoholism at a dose correspondent to 250 mg/kg via revoking hepatic cell death chains: necroptosis and pyroptosis. Thereby, opens a new avenue for assisting cellular repair mechanisms.