Effect of Agents Which Modify Reticuloendothelial System Function on Acute Phalloidin-Induced Lethality and Hepatotoxicity in Mice

Protection against phalloidin-induced liver injury by oleanolic acid involves Nrf2 activation and suppression of Oatp1b2

“…ER stress is a hallmark of phalloidin acute hepatotoxicity (Barriault et al 1995). ER stress responsive genes Gadd45 and Gadd153 (Chop10) were markedly increased following phalloidin intoxication (Fig.…”

“…Gadd45 and Chop10 activation results in signaling processes and proapoptotic events leading to hepatocellular damage (Ho et al 2005; Nagy et al 2007). Pretreatment with compounds (methyl palmitate and praseodymium nitrate) that depress ER stress have been shown to decrease phalloidin-induced hepatotoxicity (Barriault et al 1995). In the present study, increased Nrf2 signaling by genetic engineering or by pharmacological activation suppressed phalloidin-induced ER stress in the liver, indicating a potential mechanism of Nrf2 cellular protection.…”

Kupffer cell phagocytosis blockade decreases morbidity in endotoxemic rats with obstructive jaundice

“…ETX-activated liver macrophages can release reactive oxygen species, phospholipases, proteases, nitrogen radicals and cytotoxic cytokines [35]. Kupffer cell blockade induced by GdCl 3 has been reported to inhibit the secretion of these active substances and to decrease the liver damage induced by ischemia reperfusion [14], hepatotoxins [13], ETX [36] and liver transplantation [37]. Our present study also confirms the role of resident macrophages in the development of hepatocellular injury as inhibition of Kupffer cell activation protected the liver against ETX-induced structural injury in obstructive jaundice.…”

“…Our previous studies demonstrated that rare earth metal salts, including gadolinium chloride (GdCl 3 ), depress the RES activity [11], and selectively interfere with the function of the Kupffer cells [12]. It has also been reported that GdCl 3 inhibits the secretion of biologically active substances from the liver Kupffer cells, and decreases the liver-damaging effects of hepatotoxins [13], ischemia-reperfusion [14], and the development of septic shock [15].…”

Stress: From Concept to Modern Immunologya

“…Recent studies from many laboratories, including our own, have shown that the Kupffer cell blockade induced by GdCl 3 modifies immune response, 10 exerts protective effects on anaphylactic, 11 and endotoxic/septic shock, 12 and decreases the liver‐damaging effects of several hepatotoxins 13 and ischemic‐reperfusion. 14…”