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Background: Retinoid receptors (RRs), RAR-α and RXR-α, work as transcription factors that regulate cell growth, differentiation, survival, and death. Hepatic stellate cells (HSCs) store retinoid and release its RRs as lipid droplets upon their activation. Purpose: We test the hypothesis that loss of retinoid receptors RAR-α and RXR-α from HSCs is dependent on tissue factor (TF) during thioacetamide (TAA)-induced liver injury. Methods: Liver toxicity markers, TF, fibrin, cleaved caspase-3, and cyclin D1 as well as histopathology were investigated. Results: Increased TF, fibrin, cleaved caspase-3, and cyclin D1 protein expression is seen in zone of central vein after TAA injection compared with vehicle-treated mice. A strong downregulation of RAR-α and RXR-α is seen in TAA-induced liver injury. In addition, histopathological obliteration and pericentral expression of cleaved caspase 3 and cyclin D1 are observed after TAA injection compared with the normal vehicle–treated mice. No changes have been seen in TAA/TF-sense (SC) in whole parameters compared with TAA-treated animals. TAA/TF-antisense (AS)–treated mice show normal expression of all parameters and normal histopathological features when compared with the control mice. In conclusion, this study declares that the strong downregulation of RAR-α and RXR-α may cause liver injury and particularly activation of HSCs in TAA-induced toxicity. TF-AS treatment not only downregulates TF protein expression but also alleviates loss of liver RAR-α and RXR-α and suppresses the activated apoptosis signals in TAA-induced liver toxicity. Finally, TF and RAR-α/RXR-α are important regulatory molecules in TAA induced acute liver injury. [ABSTRACT FROM AUTHOR]

Rosemary (Rosmarinus officinalis; RM) and thyme (Thymus vulgaris; TV) are used as remedies. We designed this work to investigate the preventive effect of aqueous extracts of RM or TV on the gentamicin (GM)-induced hepatotoxicity and abnormalities of lipid profile in rats. Both plant extracts exhibited an in vitro antioxidant activity as determined by the 1,1-diphenyl-2-picrylhydrazyl assay. Radical scavenging activity for TV extract was 48.7% and for RM extract was 25.6%. Polyphenolic determination by high-performance liquid chromatography for both extracts revealed that catechin, coumarin, cinnamic acid and rutin were detected in both extracts. RM extract had higher values than TV extract in all except rutin. Ferulic acid and quercetin were also detected in TV extract and sinapic acid and oleuropein were detected in RM extract. In rats given GM intraperitoneally for 10 days and coadministered either RM extract or TV extract orally, both aqueous extracts demonstrated similar hepatoprotective effects manifested by approximate normalization of plasma liver enzymes (AST and ALT), bilirubin level and total protein concentration compared with the group given GM only. Abnormal lipid parameters and raised hydrogen peroxide levels were ameliorated by both extracts. Pancreatic lipase activity was markedly reduced by RM extract. Also, the atherogenic index value was significantly reduced by both extracts as compared to that of GM group. DNA fragmentation analysis confirmed tissue damage by GM and its amelioration by the extracts. These findings suggest that RM and TV extracts could be helpful in ameliorating some aspects of gentamicin toxicity. [ABSTRACT FROM AUTHOR]