RESUMEN
The cardiotoxicity induced by doxorubicin is dose-dependent. The present study tested the potential cardioprotective effect of Poly ADP Ribose Polymerase (PARP) pathway inhibitor "olaparib" in a mouse model of doxorubicin-induced cardiomyopathy (DOX-CM). Seventy-two male BALB/c mice were randomized into six equal groups; control, DOX-CM, dexrazoxane-treated, and three olaparib-treated groups (5, 10, and 50 mg/kg/day). Cardiomyopathy was assessed by heart weight/Tibial length (HW/TL) ratio, cardiac fibrosis, oxidative stress, and electron microscope. Myocardial expression of SERCA2a mRNA and cleaved PARP-1 protein were also assessed. Similar to dexrazoxane, olaparib (10 mg/kg/day) significantly ameliorated oxidative stress, and preserved cardiac structure. It also suppressed myocardial PARP-1 protein expression and boosted SERCA2a mRNA expression. Olaparib (5 or 50 mg/kg/day) failed to show comparable effects. The current study detected the cardioprotective effect of olaparib at a dosage of 10 mg/kg/day. Also, the present study discovered a new cardioprotective mechanism of dexrazoxane by targeting PARP-1 in the heart.
Asunto(s)
Cardiomiopatías , Inhibidores de Poli(ADP-Ribosa) Polimerasas , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico , Animales , Masculino , Ratones , Antineoplásicos , Cardiomiopatías/inducido químicamente , Cardiomiopatías/tratamiento farmacológico , Dexrazoxano , Doxorrubicina/toxicidad , Poli(ADP-Ribosa) Polimerasa-1/genética , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Ribosa , ARN Mensajero , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/efectos de los fármacos , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/metabolismoRESUMEN
BACKGROUND: Periocular hyperpigmentation is a condition in which skin of eyelids become darker in color than the normal surrounding skin. Lead and other heavy metals produce increased pigmentation because of deposition of metal particles in the dermis and increased epidermal melanin production. AIMS: This study was conducted to evaluate the dual effect of chelation therapy in treating periocular hyperpigmentation and lead toxicity. METHODS: The study population consisted of nine females complaining from dark coloration of their eyelids. The nine females were continuously using kohl as eyeliner. Lead levels in conjunctiva and serum before and after D-penicillamine (D-PCN) oral administration were estimated in relation to vertical, horizontal length, and degree of hyperpigmentation score. RESULTS: Highly significant P values (0.000) were obtained as regard to the conjunctival lead levels, serum lead levels, horizontal length, and degree of darkness score before and after D-PCN therapy. A less significant P value (0.040) was recorded as regard to the vertical length. CONCLUSION: Regardless other causes, this study spots the light on a new concept for periocular hyperpigmentation from lead toxicity in adult females using kohl and suggests D-PCN in a low divided dose (750 mg/day) for its treatment.
