RGFP966 inactivation of the YAP pathway attenuates cardiac dysfunction induced by prolonged hypothermic preservation / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Oxidative stress and apoptosis are the key factors that limit the hypothermic preservation time of donor hearts to within 4-6 h. The aim of this study was to investigate whether the histone deacetylase 3 (HDAC3) inhibitor RGFP966 could protect against cardiac injury induced by prolonged hypothermic preservation. Rat hearts were hypothermically preserved in Celsior solution with or without RGFP966 for 12 h followed by 60 min of reperfusion. Hemodynamic parameters during reperfusion were evaluated. The expression and phosphorylation levels of mammalian STE20-like kinase-1 (Mst1) and Yes-associated protein (YAP) were determined by western blotting. Cell apoptosis was measured by the terminal deoxynucleotidyl-transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) method. Addition of RGFP966 in Celsior solution significantly inhibited cardiac dysfunction induced by hypothermic preservation. RGFP966 inhibited the hypothermic preservation-induced increase of the phosphorylated (p)-Mst1/Mst1 and p-YAP/YAP ratios, prevented a reduction in total YAP protein expression, and increased the nuclear YAP protein level. Verteporfin (VP), a small molecular inhibitor of YAP-transcriptional enhanced associate domain (TEAD) interaction, partially abolished the protective effect of RGFP966 on cardiac function, and reduced lactate dehydrogenase activity and malondialdehyde content. RGFP966 increased superoxide dismutase, catalase, and glutathione peroxidase gene and protein expression, which was abolished by VP. RGFP966 inhibited hypothermic preservation-induced overexpression of B-cell lymphoma protein 2 (Bcl-2)-associated X (Bax) and cleaved caspase-3, increased Bcl-2 mRNA and protein expression, and reduced cardiomyocyte apoptosis. The antioxidant and anti-apoptotic effects of RGFP966 were cancelled by VP. The results suggest that supplementation of Celsior solution with RGFP966 attenuated prolonged hypothermic preservation-induced cardiac dysfunction. The mechanism may involve inhibition of oxidative stress and apoptosis via inactivation of the YAP pathway.

P-aminodiphenylamine induced biochemical changes in sex organs of male albino rats.

Intraperitoneal administration of p-aminodiphenylamine (p-ADPA), an aromatic amine of wide industrial applications, / 42.5 mg/kg body weight for 180 days significantly decreased the activities of testicular lactate dehydrogenase and hyaluronidase and lactic acid content indicating arrest of spermatogenesis. Patchy necrosis of the testis was confirmed histopathologically. No change in testicular cholesterol, fructose content of coagulating glands and dorso-lateral prostate and activities of alkaline phosphatase in seminal vesicle and acid phosphatase in ventral prostate support normal androgenic status.

Effect of Emblica officinalis Gaertn. (Indian gooseberry) fruit extract on sodium azide and 4-nitro-o-phenylenediamine induced mutagenesis in Salmonella typhimurium.

Water, acetone and chloroform extracts of E. officinalis fruit reduced sodium azide and NPD induced his+ revertants significantly in TA100 and TA97 a strains respectively of S. typhimurium. The chloroform extract was less active as compared to water and acetone extracts. Autoclaving of water extract for 15 min did not reduce its activity. The enhanced inhibitory activity of the extracts on pre-incubation suggests the possibility of desmutagens in the extracts. Besides ascorbic acid, a constituent of the extract, the role of other antimutagenic factors in the extract cannot be ruled out.