Previous study found that rifampicin caused intrahepatic cholestasis. This study investigated the effects of rifampicin on hepatic lipid metabolism. Mice were orally administered with rifampicin (200 mg/kg) daily for different periods. Results showed that serum TG level was progressively reduced after a short elevation. By contrast, hepatic TG content was markedly increased in rifampicin-treated mice. An obvious hepatic lipid accumulation, as determined by Oil Red O staining, was observed in mice treated with rifampicin for more than one week. Moreover, mRNA levels of Fas, Acc and Scd-1, several key genes for fatty acid synthesis, were elevated in rifampicin-treated mice. In addition, the class B scavenger receptor CD36 was progressively up-regulated by rifampicin. Interestingly, hepatic SREBP-1c and LXR-α, two important transcription factors that regulate genes for hepatic fatty acid synthesis, were not activated by rifampicin. Instead, hepatic PXR was rapidly activated in rifampicin-treated mice. Hepatic PPARγ, a downstream target of PXR, was transcriptionally up-regulated. Taken together, the increased hepatic lipid synthesis and uptake of fatty acids from circulation into liver jointly contribute to rifampicin-induced hepatic lipid accumulation. The increased uptake of fatty acids from circulation into liver might be partially attributed to rifampicin-induced up-regulation of PPARγ and its target genes.

No abstract

Background. Excessive acetaminophen (APAP) use can lead to acute liver injury (ALI) by inducing endoplasmic reticulum stress (ERS). We previously found that pretreatment with the peroxisome proliferator-activated receptor-γ (PPAR-γ) ligand rosiglitazone (RSG) alleviated ALI in APAP-treated mice. Objective. To examine if RSG-mediated hepatoprotection is associated with ERS suppression. Methods. Forty-eight male CD-1 mice were randomly divided into control, RSG, APAP 4 h, APAP 24 h, RSG + APAP 4 h, and RSG + APAP 24 h groups. The RSG and RSG + APAP groups received RSG (20 mg/kg) by gavage 48, 24, and 1 h before intraperitoneal injection of 300 mg/kg APAP, while the APAP group received APAP alone and the control group received only normal saline. Animals were sacrificed immediately (RSG and control groups), 4 h (APAP 4 h and RSG + APAP 4 h), or 24 h (APAP 24 h and RSG + APAP 24 h) post-APAP injection. Liver tissues were collected for hematoxylin-eosin staining, TUNEL staining, and Western blotting for ERS-associated proteins. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were also measured. A second cohort received APAP or RSG + APAP as described and were monitored for survival over one week. Results. At 4 and 24 h following APAP injection alone, serum ALT and AST levels were significantly elevated, and central lobular necrosis of the liver was observed. Necrosis area reached 21.7% at 4 h and 32.1% at 24 h post-APAP, while apoptotic fractions reached 25.6% and 32.4%. Further, 50% of mice in the survival analysis cohort died within one week post-APAP. At 4 h post-APAP, the ERS marker glucose-regulated protein-78 (GRP78) and ERS-associated proteins pJNK, GRP78, p-eIF2α, pPERK, and pIRE were all significantly upregulated. Pretreatment with RSG significantly reduced serum ALT and AST, liver necrosis area, apoptosis rate, and expression of ERS-associated proteins compared to APAP alone, while increasing survival to 80%. Conclusions. Rosiglitazone pretreatment can alleviate APAP-induced ALI by suppressing three branches of ERS signaling.

<span>Nerve injury commonly contributes to irreversible functional impairment, reconstruction of the function of muscle is big challenge. In denervated skeletal muscle, therapid expression of MyoD mRNA and protein also occurs during early postdenervation, which suggested that the function of denervation-induced MyoD may be to prevent denervation-induced skeletal muscle atrophy. However, the detail mechanism is not clear. Therefore, in this study, we established a stable-transfected MyoD L6 cell line. After the operation for cutting the rats’ tibial nerve, the MyoD-L6 cells were injected in the gastrocnemius, the function of the gastronemius was monitored. It was found that injected the MyoD-L6 cells could attenuate the muscle atrophy and dysfunction. Therefore, overexpression of MyoD could serve as a new therapy strategy to cure denervation-induced dysfunction of skeletal muscle.</span><span></span>