RESUMEN
Acetoacetate (AA) is a ketone body, which generates reactive oxygen species (ROS). ROS production is impacted by the formation of covalent bonds between amino groups of biomacromolecules and reducing sugars (glycation). Glycation can damage DNA by causing strand breaks, mutations, and changes in gene expression. DNA damage could contribute to the pathogenesis of various diseases, including neurological disorders, complications of diabetes, and aging. Here we studied the enhancement of glucose-mediated DNA glycation by AA for the first time. The effect of AA on the structural changes, Amadori and advanced glycation end products (AGEs) formation of DNA incubated with glucose for 4 weeks were investigated using various techniques. These included UV-Vis, circular dichroism (CD) and fluorescence spectroscopy, and agarose gel electrophoresis. The results of UV-Vis and fluorescence spectroscopy confirmed that AA increased the DNA-AGE formation. The NBT test showed that AA also increased Amadori product formation of glycated DNA. Based on the CD and agarose gel electrophoresis results, the structural changes of glycated DNA was increased in the presence of AA. The chemiluminescence results indicated that AA increased ROS formation. Thus AA has an activator role in DNA glycation, which could enhance the adverse effects of glycation under high glucose conditions.
RESUMEN
Lead affects multiple organ systems including testis. We investigated the effects of ferulic acid (FA) on lead-induced oxidative stress and spermatogenesis suppression in rats. Animals received lead acetate (500 mg/L in drinking water) and/or FA (50 mg/kg, i.g.) for eight weeks. Lead increased testicular malondialdehyde (MDA) and nitrite levels and decreased glutathione (GSH) content and catalase (CAT) activity. Lead decreased testis weight and testosterone level. Sperm parameters decreased in lead group. FA ameliorated the decreased testis weight, serum testosterone as well as sperm count, viability, motility and normal morphology in lead group. FA improved antioxidant capacity as well as sperm count, viability, motility and normal morphology. FA decreased Johnsen's mean testicular biopsy score (MTBS) criteria by restoring degeneration, atrophy and tubular disarrangement. FA also normalised spermatogonia, spermatocytes and spermatids numbers in lead group and led to increases in number of Leydig and Sertoli cells. FA showed beneficial effects in lead-induced testicular oxidative stress and spermatological disorders, through inhibiting lipid peroxidation and enhancing antioxidant defence systems. The positive effects of FA on Leydig cells may be involved in restoring testosterone levels in lead group. FA can be considered a potential candidate to protect testis against the deleterious effect of lead intoxication.
Asunto(s)
Ácidos Cumáricos/farmacología , Compuestos Organometálicos/administración & dosificación , Estrés Oxidativo/efectos de los fármacos , Espermatogénesis/efectos de los fármacos , Espermatozoides/efectos de los fármacos , Testículo/efectos de los fármacos , Animales , Peroxidación de Lípido/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Ratas , Testículo/metabolismoRESUMEN
Oxidative stress is among the mechanisms involved in renal injury. We aimed to investigate the protective effects of bioactive peptide carnosine on lead induced oxidative stress and nephrotoxicity in rats. Animals received an aqueous solution of lead acetate (500 mg Pb/L in the drinking water) and/or carnosine (10 mg/kg, i.g.) for eight weeks. Then rats were weighed and used for biochemical, histological and oxidant/antioxidant evaluations. Lead-induced oxidative stress in renal tissue was indicated by a significant increase in the renal contents of malondialdehyde (MDA) as well as decrease in the levels of reduced glutathione (GSH), total antioxidant capacity (TAC), catalase (CAT) and superoxide dismutase (SOD) (P's < 0.001). Carnosine treatment decreased MDA whereas it increased the contents of GSH, TAC, CAT and SOD in both lead and control groups. Carnosine prevented the increased kidney weight and lead-induced deleterious effects on serum creatinine, urea, uric acid, albumin and total protein in lead group. It also attenuated lead induced abnormal renal structure. The present study showed that carnosine protected against lead induced oxidative stress and renal injury in rat. Therefore, carnosine represents a potential therapeutic option against the deleterious effect of lead induced nephrotoxicity which deserves consideration and further examination.