ABSTRACT
Tissue factor (TF) activates the coagulation system and has an important role in the pathogenesis of various diseases. Our previous study stated that retinoid receptors (RAR-α and RXR-α) are released as a lipid droplet in monocrotaline/ lipopolysaccharide-induced idiosyncratic liver toxicity in mice. Herein, the interdependence between the release of retinoid receptors RAR-α and RXR-α and TF in Nacetyl-p-aminophenol (APAP)-induced mice liver toxicity, is investigated. Serum alanine transaminase (ALT) level, platelet and white blood cells (WBCs) counts, protein expression of fibrin, TF, cyclin D1 and cleaved caspase-3 in liver tissues are analyzed. In addition, histopathological evaluation and survival study are also performed. The results indicate that using of TF-antisense (TF-AS) deoxyoligonucleotide (ODN) injection (6 mg/kg), to block TF protein synthesis, significantly restores the elevated level of ALT and WBCs and corrects thrombocytopenia in mice injected with APAP. TF-AS prevents the peri-central overexpression of liver TF, fibrin, cyclin D1 and cleaved caspase-3. The release of RXR-α and RAR-α droplets, in APAP treated sections, is inhibited upon treatment with TF-AS. In conclusion, the above findings designate that the released RXR-α and RAR-α in APAP liver toxicity is TF dependent. Additionally, the enhancement of cyclin D1 to caspase-3-dependent apoptosis can be prevented by blocking of TF protein synthesis.
ABSTRACT
Tissue factor (TF) activates the coagulation system and has an important role in the pathogenesis of various diseases. Our previous study stated that retinoid receptors (RAR-α and RXR-α) are released as a lipid droplet in monocrotaline/ lipopolysaccharide-induced idiosyncratic liver toxicity in mice. Herein, the interdependence between the release of retinoid receptors RAR-α and RXR-α and TF in Nacetyl-p-aminophenol (APAP)-induced mice liver toxicity, is investigated. Serum alanine transaminase (ALT) level, platelet and white blood cells (WBCs) counts, protein expression of fibrin, TF, cyclin D1 and cleaved caspase-3 in liver tissues are analyzed. In addition, histopathological evaluation and survival study are also performed. The results indicate that using of TF-antisense (TF-AS) deoxyoligonucleotide (ODN) injection (6 mg/kg), to block TF protein synthesis, significantly restores the elevated level of ALT and WBCs and corrects thrombocytopenia in mice injected with APAP. TF-AS prevents the peri-central overexpression of liver TF, fibrin, cyclin D1 and cleaved caspase-3. The release of RXR-α and RAR-α droplets, in APAP treated sections, is inhibited upon treatment with TF-AS. In conclusion, the above findings designate that the released RXR-α and RAR-α in APAP liver toxicity is TF dependent. Additionally, the enhancement of cyclin D1 to caspase-3-dependent apoptosis can be prevented by blocking of TF protein synthesis.
ABSTRACT
Addition of curcumin in concentrations of 1.4 x 10-5 M, 2.8 x 10-5 M and 5.6 x 10-5 M to the organ bath, resulted in significant inhibitions in the normal uterine contractions of non-pregnant rats in the diestrus stage. The recorded decline in the frequency of uterine contractions were 32%, 47% and 67%, while the inhibitions were 50%, 67% and 76% for the amplitude respectively. The reductions in area under the curve [AUC] of contractions were 67%, 71% and 86% for the added concentrations. Pretreatment with curcumin revealed inhibitory effects on the uterine response to oxytocin [10-11M] amounting to 77%, 78% and 72% in AUC with respect to that obtained post-addition of oxytocin alone. These results indicate that the tocolytic potential of curcumin may involve oxytocin receptor-dependent pathway
Subject(s)
Animals, Laboratory , Uterus/drug effects , Oxytocin , Uterine Contraction/drug effects , RatsABSTRACT
Addition of curcumin in concentrations of 1.4 x 10[-5] M, 2.8 x 10[-5] M and 5.6 x 10 [-5]M to the organ bath, resulted in significant inhibitions in the normal uterine contractions of non-pregnant rats in the diestrus stage. The recorded decreases in frequencies of uterine contractions were 32%, 47% and 67%, while the inhibitions were 50%, 67% and 76% for the amplitude, respectively. The reductions in area under the curve [AUC] of contractions were 67%, 71% and 86% for the added concentrations, respectively. Pretreatment with curcumin in the previous concentrations revealed inhibitory effects on the uterine response to oxytocin [10[-11]M] amounting to 77%, 78% and 72% in AUC with respect to that obtained post-addition of oxytocin alone. These results indicate that the tocolytic potential of curcumin may involve oxytocin receptor-dependent pathway