RESUMEN
This study aimed to investigate the preventive and protective effects of silymarin (SMN) on doxorubicin (DOX)-induced damages in the testis. Wistar rats were divided into six groups (n=8), including: control (C), DOX-treated (DOX, 15 mg/kg, i.p.), DOX- and SMN-treated and SMN-treated animals (SMN, 50 mg/kg, orally). Those groups, which received either compounds, were sub-grouped based on the preventive (PVT), protective (PTT) and/or therapeutic regimens (TPT) of SMN administration. The antioxidant status analyses, hormonal assay, and histopathological examinations in the testis were conducted. The expression of c-myc at mRNA level also was analyzed. SMN in preventive and protective forms significantly (p<0.05) improved the DOX-induced weight loss and lowered the alkaline phosphatase level. Pretreatment and co-treatment with SMN attenuated the DOX-induced carbonyl stress. The DOX-induced histopathological damages including negative TDI and IR were significantly (p<0.05) improved with SMN pretreatment and co-administration. SMN in preventive and protective forms prevented from DOX-induced DNA fragmentation in the testis. SMN ameliorated the DOX-reduced serum level of sexual hormones including testosterone, inhibin B, LH and FSH in PVT and PTT groups. The c-myc expression at mRNA level was completely and relatively down regulated in the testis of animals that received SMN as pretreatment and concurrent administration, respectively. Our data suggests that the DOX-induced biochemical and histopathological alterations could be prevented and/or protected by SMN. Moreover, the SMN protective and preventive effects attribute to its capacity in the reduction of DOX-induced carbonyl stress and DNA damage, which may be mediated by c-myc expression.
Asunto(s)
Expresión Génica/efectos de los fármacos , Fitoterapia , Proteínas Proto-Oncogénicas c-myc/metabolismo , Silybum marianum/química , Silimarina/uso terapéutico , Enfermedades Testiculares/tratamiento farmacológico , Testículo/efectos de los fármacos , Fosfatasa Alcalina/sangre , Animales , Fragmentación del ADN/efectos de los fármacos , Regulación hacia Abajo , Doxorrubicina , Genes myc , Hormonas Esteroides Gonadales/sangre , Masculino , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Carbonilación Proteica/efectos de los fármacos , Proteínas Proto-Oncogénicas c-myc/genética , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Silimarina/farmacología , Enfermedades Testiculares/genética , Enfermedades Testiculares/metabolismo , Enfermedades Testiculares/patología , Testículo/metabolismo , Testículo/patología , Pérdida de Peso/efectos de los fármacosRESUMEN
This study was designed to clarify the molecular mechanism(s) of mycophenolate mofetil (MMF)- induced gastrointestinal (GI) disorders. Forty-two adult Wistar rats were assigned to 7 groups including control and test hosts. The control animals received normal saline and the test animals various doses of MMF (10, 20, or 40 mg/kg) for 14 days, or MMF, aspirin, or lipopolysaccharide as single high doses (40, 200, and 1 mg/kg, respectively). To evaluate the GI disorders, are determined body weight gain, serum level of alkaline phosphatase (ALP), nitric oxide (NO), and acute phase proteins (APP). Additionally, we measured the duodenal NO content and myeloperoxidase activity. MMF administration resulted in a significant (P < .05) body weight loss and elevation of serum levels of ALP and NO. The duodenal NO content increased in the test groups with the highest levels among the aspirin-treated cohort. The myeloperoxidase activity and the serum level of APP were elevated among MMF- and aspirin-treated animals. Histopathologic examinations showed villous atrophy and inflammatory cells infiltration among MMF-treated animals. Our data suggested that the MMF-induced GI disorders were likely related to local inflammatory reactions, which may be attributed to elevated NO and myeloperoxidase activities that result in pathological injuries. Moreover, the biochemical alterations and histopathologic injuries due to MMF administration were similar to aspirin-induced local disorders rather than to lipopolysaccharide-induced systemic damage.