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The role of n-3 polyunsaturated fatty acids (PUFAs) in alcoholic liver disease (ALD) has been controversial. N-3 PUFA oxidation in animal feeding stuffs was rarely concerned, likely contributing to inconsistent outcomes. Here, we report the impacts of oxidized fish oil (OFO) on ALD in C57BL/6 mice. Alcohol exposure increased plasma aminotransferase levels and hepatic inflammation. These deleterious effects were ameliorated by unoxidized FO but exacerbated by OFO. Sequencing analysis showed the accentuated intestinal dysbiosis and the increased proportion of Proteobacteria in OFO-fed mice. Intestinal sterilization by antibiotics completely abolished OFO-aggravated liver injury. Additionally, alcohol exposure leads to the greater increase in plasma endotoxin and decrease in intestinal tight junction protein expressions in OFO-fed mice. Stabilization of intestinal barrier by obeticholic acid markedly blunted OFO-aggravated liver injury in alcohol-fed mice. These results demonstrate that OFO exacerbates alcoholic liver injury through enhancing intestinal dysbiosis, barrier dysfunction, and hepatic inflammation mediated by gut-derived endotoxin.

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Andrographolide (AND) has wide prospects in clinical use, but suffers from the restriction of poor oral bioavailability, due to its low solubility, rapid and extensive metabolism and efflux by P-glycoprotein (P-gp).

Phospholipid hydroperoxide glutathione peroxidase (PHGPx), as a ubiquitous antioxidant enzyme in the glutathione peroxidases (GPx) family, plays multiple roles in organisms. However, there is very little information on PHGPx in goats (Capra hircus). In this study, a full-length cDNA was cloned and characterized from Taihang black goat testes. The 844 bp cDNA contains an open reading frame (ORF) of 597 bp. The goat PHGPx nucleotide sequence contains a selenocysteine (sec) codon TGA244-246, two potential start codons ATG20-22 and ATG108-110, a polyadenylation signal AATAAA813-818 and selenocysteine insertion sequence (SECIS) motif AUGA688-691, UGA729-731 and AAA703-705. As a selenoprotein, the active-site motifs and GPx family signature motifs LAFPCNQF101-108 and WNFEK165-170 were also found. The order of PHGPx mRNA expression levels was: testes >> heart > brain > epididymis > kidney > liver > lung > spleen > muscle. Real-time PCR and immunohistochemistry results revealed similar expression differences in different age testes, with high expression levels during adolescence. Immunofluorescence results suggested that PHGPx mainly expressed in Leydig cells and spermatids in mature goat testes.