Lipopolysaccharide-induced hepatic injury is enhanced by polychlorinated biphenyls.

Abstract

After intravenous administration of bacterial lipopolysaccharide (LPS) to rats, polymorphonuclear neutrophils (PMNs) rapidly accumulate in the liver, and midzonal hepatic necrosis is prominent by 6 hr. PMNs are required for the development of hepatic injury in rats. Certain polychlorinated biphenyls (PCBs) can activate PMNs, resulting in production of superoxide anion (O2-.) and release of cytolytic factors from granules. This raises the possibility that PCB exposure might enhance PMN-mediated tissue injury, such as LPS-induced hepatotoxicity. We treated female Sprague-Dawley rats with a minimally toxic dose of LPS in saline (2 mg/kg, intravenous) and 90 min later exposed them to Aroclor 1248 (50 mg/kg, intraperitoneal), a mixture of PCBs. The animals were killed 6 hr after LPS administration, and hepatic injury was assessed. Neither LPS nor Aroclor 1248 alone produced liver injury. Co-treatment with LPS and Aroclor 1248 resulted in pronounced liver injury as demonstrated from increased activities of alanine aminotransferase and isocitrate dehydrogenase in plasma. Histological evaluation indicated increased severity of hepatic necrosis in rats receiving both LPS and Aroclor 1248. Hepatic accumulation of PMNs, normally observed after LPS, was not altered by co-exposure to PCBs. Aroclor 1248 stimulated rat PMNs in vitro to produce O2-. and to degranulate. In addition, PMN-mediated cytotoxicity to isolated rat hepatocytes in culture was increased upon addition of Aroclor 1248. PCBs activate PMNs in vitro and increase PMN-dependent hepatocellular damage in vitro and after LPS treatment in vivo. PCBs may act in vivo as an additional inflammatory stimulus to activate PMNs to become cytotoxic, resulting in increased tissue injury.ImagesFigure 1.Figure 2. AFigure 2. BFigure 3.Figure 4. AFigure 4. BFigure 5.Figure 6.

Resveratrol and Curcumin Improve Intestinal Mucosal Integrity and Decrease m6A RNA Methylation in the Intestine of Weaning Piglets

“…After weaning, Gram-negative bacteria proliferate in large numbers, and the impaired intestinal epithelium leads to the release of endotoxin into the intestinal mucosa and systematic circulation and then accumulates in the liver. 44 Researchers have found that intraperitoneal injection of lipopolysaccharide leads to an increased level of liver m 6 A in chicken 45 and weaned piglets. 21 The decreased intestinal bacterial population may be one of the causes of decreased m 6 A levels in the intestinal mucosa.…”

Age-related bias in function of natural killer T cells and granulocytes after stress: reciprocal association of steroid hormones and sympathetic nerves

“…It is well established that granulocytes are the main source of cells for superoxide production [40,41]. It is also known that activated granulocytes or neutrophils are intimately related to tissue damage, including that of the liver, lung and other organs [42–44].…”

Dexamethasone Pretreatment Alleviates Isoniazid/Lipopolysaccharide Hepatotoxicity: Inhibition of Inflammatory and Oxidative Stress

“…Episodes of modest inflammation, although benign on their own, are probably commonplace in people and have the ability to augment the toxicities of several xenobiotic agents ( Liu et al, 2000 ; Lu et al, 2011 ). Indeed, it has been suggested that exposure to endogenous LPS due to increased movement of bacteria across a compromised intestinal mucosa contributes to the hepatotoxicity produced by various agent ( Brown et al, 1996 ; Barton et al, 2000 ; Yee et al, 2000 ). Moreover, LPS influences the pharmacokinetics of drugs ( Ma et al, 2011 ) by modulating the activities of both phase I ( Pan et al, 2003 ; Xu et al, 2006 ) and phase II ( Richardson et al, 2006 ; Alkharfy et al, 2008 ) drug-metabolizing enzymes.…”