RESUMEN
The widespread use of acetaminophen (APAP) in children as an over-the-counter treatment can cause acute liver failure through accidental overdose or ingestion. Therefore, the current research sought to investigate the function of hemin in mitigating the acute hepatotoxic effect of APAP in rat offspring. Thirty-two rats were assigned into four groups: control, hemin, APAP, and hemin/APAP groups. Liver enzymes were measured in serum along with oxidative stress indicators, tumor necrosis factor-α (TNF-α), interleukin-1beta (IL-1ß), total nitrites (NOx), and caspase 3 in liver. Immunoblotting of heme oxygenase-1 (HO-1), interleukin-6 (IL-6), Janus kinase 2 (Jak2), and signal transducer and activator of transcription 3 (STAT3) was carried out. The Bax/Bcl2 mRNA expression ratio was determined. A histological study and an immunohistochemical study of phosphorylated STAT3 were also done. Hemin reduced liver enzymes, MDA, TNF-α, NOx, caspase 3, IL-1ß, p-STAT3 expression, p-Jak2 expression, IL-6 expression, and Bax/Bcl2 mRNA expression ratio. In contrast, hemin increased GSH, TAC, and the expression of HO-1, improving the histopathological picture of liver tissue. Thus, hemin could ameliorate APAP-induced hepatic toxicity in rat offspring through anti-oxidant, anti-apoptotic, and anti-inflammatory actions with a possible role for the IL-6/HO-1/Jak2/STAT3 pathway.
Asunto(s)
Acetaminofén , Enfermedad Hepática Inducida por Sustancias y Drogas , Ratas , Animales , Acetaminofén/toxicidad , Hemo-Oxigenasa 1/genética , Hemo-Oxigenasa 1/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Animales Recién Nacidos , Caspasa 3/genética , Caspasa 3/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Hemina/farmacología , Proteína X Asociada a bcl-2/metabolismo , Hígado , Transducción de Señal , ARN Mensajero , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Enfermedad Hepática Inducida por Sustancias y Drogas/patologíaRESUMEN
Testicular torsion is an emergency, mainly in newborn and adolescent males, resulting in testicular ischemia. The current study aimed to evaluate the effect of Idebenone (IDE) on testicular torsion/detorsion (T/D) in juvenile rats. Thirty-two rats were randomized into: (1) the sham group: rats received sham operations with no other interventions; (2) the IDE group: rats received idebenone (100 mg/kg, i. p) without T/D; (3) the T/D group: rats underwent torsion for 2 h and detorsion for 4 h; and (4) the IDE+ T/D group: rats received IDE 1 h before T/D. Testicular malondialdehyde (MDA), total nitrite/nitrate (NOx), total antioxidant capacity (TAC), tumor necrosis factor-α (TNF-α), caspase-3, sirtuin type 1 (Sirt1), serum interleukin-1ß (IL-1ß), total cholesterol, and testosterone were measured. Histological changes, nuclear factor (erythroid-derived 2)-like-2 factors (Nrf2), and proliferating cell nuclear antigen (PCNA) immuno-expressions were assessed. T/D displayed an increase in MDA, NOx, TNF-α, caspase-3, IL-1ß, and total cholesterol with a significant decrease in TAC, Sirt1, and testosterone and strong positive Nrf2 and negative PCNA immuno-expressions. IDE could improve all oxidative, inflammatory, and apoptotic indicators. Therefore, IDE significantly reduced testicular ischemia-reperfusion injury in the juvenile rat testicular T/D model by limiting oxidative stress, inflammation, and apoptosis via the Sirt1/Nrf2/TNF-α pathway.
Asunto(s)
Daño por Reperfusión , Torsión del Cordón Espermático , Adolescente , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Apoptosis , Caspasa 3/metabolismo , Colesterol , Humanos , Inflamación/metabolismo , Masculino , Malondialdehído/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo , Antígeno Nuclear de Célula en Proliferación/metabolismo , Ratas , Ratas Wistar , Daño por Reperfusión/metabolismo , Sirtuina 1/metabolismo , Torsión del Cordón Espermático/tratamiento farmacológico , Torsión del Cordón Espermático/metabolismo , Torsión del Cordón Espermático/patología , Testículo , Testosterona/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Ubiquinona/análogos & derivadosRESUMEN
Purpose: Nowadays, there is a dramatic increase in the interest of potential impact of consumer-relevant engineered nanoparticles on pregnancy.Materials and methods: This study investigated the possible protective effect of montelukast in neonatal organ toxicity induced by maternal exposure to silver nanoparticles (AgNPs) in rats.Results: It was noticed that montelukast reduced serum urea, creatinine, renal caspase-3 immunoreactivity and IL-1ß and increased total antioxidant capacity, as compared to AgNPs. In kidney and bone tissue, montelukast reduced oxidative stress parameters and TNF-α level that was increased with AgNPs. Surprisingly, montelukast administration increased epidermal growth factor (EGF) in bone and reduced it in kidney. Furthermore, as compared to AgNPs, montelukast improved histopathological picture of kidney and bone.Conclusions: In conclusion, montelukast antagonized the biochemical and histopathological changes occurred in kidneys and bones of rat offspring by maternal exposure to AgNPs, mostly by anti-oxidant, anti-apoptotic and anti-inflammatory actions with a possible role for EGF.