RESUMEN
In the past few decades, there has been much concern about the adverse health effects of environmental contaminants in general and Crude Oil in particular around the Niger Delta region of Nigeria where all the crude Oil exploration is taking place. Studies have shown the repro-toxic effects of Bonny-light crude oil (BLCO). However, the insight into the mechanisms of gonadal toxicity induced by BLCO is not well known. In this study, we sought to elucidate the mechanism(s) underpinning the gonadal effects within hours of exposure to BLCO. Experimental rats were divided into five groups of four each. Animals were orally administered with a single dose of BLCO (800 mg/kg body weight) and killed at 0, 6, 12, 24, and 72 h post-treatment. The levels and time-course of induction of stress response proteins and apoptosis-related proteins like cytochorome C, caspase 3 and procaspase 9, Fas-FasL, NF-kB and TNF-α were determined to assess sequential induction of apoptosis in the rat testis. DNA damage was assessed by TUNEL assay. Administration of BLCO resulted in a significant increase in the levels of stress response proteins and apoptotis- related proteins as early as 6 h following exposure. Time-dependent elevations in the levels of the proteins were observed. The DNA damage was measured and showed time-dependent increase in the TUNEL positive cells of testicular cells. The study demonstrates induction of testicular apoptosis in adult rats following exposure to a single dose of BLCO.
Asunto(s)
Apoptosis/efectos de los fármacos , Caspasa 3/efectos de los fármacos , Proteínas de Choque Térmico/biosíntesis , Petróleo/toxicidad , Testículo/metabolismo , Animales , Proteínas Reguladoras de la Apoptosis/metabolismo , Daño del ADN , Contaminantes Ambientales/toxicidad , Etiquetado Corte-Fin in Situ , Masculino , Nigeria , Ratas , Ratas Wistar , Testículo/efectos de los fármacosRESUMEN
Testicular steroidogenesis has significant implication in male reproductive function. Although the effects of various signalling molecules on testicular functions have been studied earlier, the influence of the plant hormone gibberellic acid (GA3 ) on steroidogenesis has not been investigated. Acute (4 h) and subacute (15 days) studies using this compound through oral administration (150 µg day(-1) ) to groups of normal and diabetic Wistar male rats were therefore carried out. Results indicate that (i) enhanced activity of steroidogenic markers 3ß-hydroxysteroid dehydrogenase (3ß-HSD), 17ß-hydroxysteroid dehydrogenase (17ß-HSD), elevated tissue testosterone (T) content, increased steroidogenic acute regulatory protein (StAR) and androgen binding protein (ABP) levels with reduced lipid peroxidation and improved antioxidant defence in this treatment group of normal and diabetic rat testis, and (ii) elevated lipid peroxidation and diminished antioxidant defence, with insignificant change in 3ß-HSD and 17ß-HSD activity and testosterone level in acute treatment group of normal and diabetic rats testis, were noted. The observed increase in the activity of testicular 3ß-HSD and 17ß-HSD along with elevated testosterone content established GA3 as an inducer of steroidogenesis in rat.
Asunto(s)
Giberelinas/farmacología , Hormonas Esteroides Gonadales/biosíntesis , Reguladores del Crecimiento de las Plantas/farmacología , Testículo/efectos de los fármacos , 17-Hidroxiesteroide Deshidrogenasas/metabolismo , 3-Hidroxiesteroide Deshidrogenasas/metabolismo , Proteína de Unión a Andrógenos/metabolismo , Animales , Antioxidantes/metabolismo , Diabetes Mellitus Experimental/metabolismo , Evaluación Preclínica de Medicamentos , Peroxidación de Lípido/efectos de los fármacos , Masculino , Fosfoproteínas/metabolismo , Ratas Wistar , Testículo/metabolismoRESUMEN
The study evaluated the protective role of kolaviron (an isolated biflavonoid from the seed of Garcinia kola) and vitamin E in carbendazim-induced reproductive dysfunction in male rats. Adult male Wistar rats were orally exposed to carbendazim (200mg/kg) singly or in combination with kolaviron (100 and 200mg/kg). Exposure to carbendazim significantly decreased the activities of superoxide dismutase and catalase but markedly increased sialic acid concentration and lipid peroxidation in the testes of rats. Western blot analysis revealed that carbendazim treatment decreased the expression of steroid acute regulatory (StAR) protein and androgen binding protein (ABP) with concomitant decrease in activities of steroidogenic enzymes. Germ cell apoptosis in carbendazim-treated rats was confirmed by TUNEL assay. However, pretreatment with kolaviron and vitamin E restored the testicular antioxidant status and steroidogenesis and decreased apoptotic nuclei to near control level in carbendazim-treated rats. Kolaviron may prove useful in combating carbendazim-induced reproductive toxicity.
Asunto(s)
Bencimidazoles/toxicidad , Carbamatos/toxicidad , Flavonoides/farmacología , Fungicidas Industriales/toxicidad , Testículo/efectos de los fármacos , 3-Hidroxiesteroide Deshidrogenasas/metabolismo , Proteína de Unión a Andrógenos/metabolismo , Animales , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Catalasa/metabolismo , Citocromos c/metabolismo , Estradiol Deshidrogenasas/metabolismo , Flavonoides/aislamiento & purificación , Garcinia kola , Masculino , Ácido N-Acetilneuramínico/metabolismo , Fosfoproteínas/metabolismo , Extractos Vegetales/química , Ratas , Ratas Wistar , Semillas , Superóxido Dismutasa/metabolismo , Testículo/metabolismo , Receptor fas/metabolismoRESUMEN
Nonylphenol (NP) is an environmental contaminant known to possess estrogenic properties. Humans are constantly exposed to NP by contaminated water and food products. In the present study we sought to investigate whether treatment with low doses of NP induces apoptosis in the liver of adult rats. Rats were administered with NP by oral gavage at the doses of 15,150 and 1500 µg/kg body weight per day for 45 days. Plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were assayed. Apoptosis-related proteins namely cytochrome c, caspase-3, caspase-8, caspase-9, Fas and Fas-l, and expression of bcl-2 mRNA and bax mRNA were examined in the liver. Levels of AST and ALT were increased in the treated rats. Western blot analysis revealed elevation in the levels of cytochrome c, caspase-3, caspase-8, caspase-9, Fas and Fas-l in the liver of NP-treated rats. Decreased expression of bcl-2 mRNA (anti-apoptotic) and increased expression of bax mRNA (apoptotic) were observed in the liver of treated rats. Increased localization of caspase-3 in the hepatocytes and DNA damage were observed in the liver of treated rat. It is concluded that NP induces apoptosis in liver involving both mitochondria-dependent and Fas-Fas-l pathways and thereby, leading to hepatic damage in rats.
Asunto(s)
Apoptosis/fisiología , Proteína Ligando Fas/fisiología , Hígado/fisiología , Mitocondrias/fisiología , Fenoles/toxicidad , Transducción de Señal/fisiología , Animales , Apoptosis/efectos de los fármacos , Fragmentación del ADN/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Mitocondrias/efectos de los fármacos , Mitocondrias/patología , Ratas , Ratas Wistar , Transducción de Señal/efectos de los fármacosRESUMEN
In the present study, we sought to investigate the long-term effects of nonylphenol (NP) on insulin signaling and glucose metabolism in liver. Furthermore, reactive oxygen species (ROS) in liver was evaluated as it is known to induce insulin resistance. Rats were administered NP by oral gavage at the doses of 15, 150 and 1500 µg/ kg body weight per day for 45 days. Hydrogen peroxide (H(2)O(2)) generation and lipid peroxidation were increased, and the activities of antioxidant enzymes were decreased in the liver of NP-treated rats. NP increased the plasma glucose and insulin levels and altered the enzymes of carbohydrate metabolism. Decrease in the protein levels of insulin signaling molecules insulin receptor (IR), IR substrate (IRS)-1, IRS-2 and phosphatidylinositol-3-kinase were observed with parallel increase in H(2)O(2) levels in the liver of NP-treated rats. These results suggest that NP downregulates insulin signaling in liver, which could be due to ROS production and oxidative damage.
Asunto(s)
Contaminantes Ambientales/toxicidad , Insulina/metabolismo , Hígado/efectos de los fármacos , Fenoles/toxicidad , Animales , Glucemia/análisis , Catalasa/metabolismo , Glucosa/metabolismo , Peróxido de Hidrógeno/metabolismo , Proteínas Sustrato del Receptor de Insulina/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Hígado/metabolismo , Masculino , Estrés Oxidativo/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Ratas , Ratas Wistar , Receptor de Insulina/metabolismo , Superóxido Dismutasa/metabolismoRESUMEN
Bisphenol A (BPA), a monomer present in plastics, is known to impair male reproductive functions. Testis executes high-energy-demanding processes such as spermatogenesis and steroidogenesis, the successful accomplishment of which requires several factors including glucose. In this context, we sought to investigate the effects of low doses of BPA on glucose metabolism in the testis of rats and to delineate whether oxidative stress has any role to play in mediating the effects. Bisphenol A was orally administered to rats at dose levels of 0.005, 0.5, 50, and 500 µg/kg body weight for 45 days. A positive control was maintained by orally administering 17ß-estradiol at a dose of 50 µg/kg body weight. The levels of plasma glucose and insulin were significantly increased, whereas the testicular glucose level significantly decreased following exposure to BPA and estradiol. A dose-dependent increase in the level of hydrogen peroxide (H2O2) and a significant decline in the activities of hexokinase and phosphofructokinase was observed in the testis of rats treated with BPA. Western blot analyses of insulin receptor substrate 2 (IRS-2) and glucose transporter 8 (GLUT-8) in the testis showed a decline in the levels of these proteins following BPA administration. Immunolocalization of GLUT-8 protein in the testis revealed decreased expression of this protein in spermatocytes and developing spermatids of rats exposed to BPA. The results suggest that persistent exposure to low doses of BPA could disturb glucose homeostasis in the testis and thereby impair testicular functions.
Asunto(s)
Regulación hacia Abajo/efectos de los fármacos , Disruptores Endocrinos/toxicidad , Proteínas Facilitadoras del Transporte de la Glucosa/metabolismo , Proteínas Sustrato del Receptor de Insulina/metabolismo , Estrés Oxidativo/efectos de los fármacos , Fenoles/toxicidad , Testículo/efectos de los fármacos , Animales , Compuestos de Bencidrilo , Relación Dosis-Respuesta a Droga , Disruptores Endocrinos/administración & dosificación , Proteínas Facilitadoras del Transporte de la Glucosa/antagonistas & inhibidores , Proteínas Sustrato del Receptor de Insulina/antagonistas & inhibidores , Masculino , Fenoles/administración & dosificación , Ratas , Ratas Wistar , Testículo/metabolismoRESUMEN
Nonylphenol is known to have estrogenic properties and has been reported to cause health hazards to animals and humans. The effects of nonylphenol on pancreas are not clearly elucidated. In this study, we sought to evaluate the effects of nonylphenol on the oxidative status of pancreas and consequential effects of nonylphenol on some of the end points of carbohydrate metabolism in the female rats. Rats were administered nonylphenol orally at the doses of 1.5, 15, and 150 mg/kg of body weight per day for 7 days. After 24 h of last dosing, the animals were sacrificed by cervical dislocation. The activities of pancreatic superoxide dismutase and catalase were significantly decreased with a concomitant increase in the levels of H2O2 and lipid peroxidation. Nonylphenol increased plasma insulin levels with a concomitant decrease in the levels of plasma glucose as compared to the control groups of rats. A dose-dependent increase in the activities of liver hexokinase and phosphofructokinase was recorded along with decreased activity of glycogen phosphorylase in liver. Western blot analysis revealed a significant decrease in the levels of GLUT-2. These results show that nonylphenol causes oxidative stress in pancreas and impairs liver glucose homeostasis.
Asunto(s)
Glucosa/metabolismo , Inactivación Metabólica , Hígado/efectos de los fármacos , Estrés Oxidativo , Páncreas/efectos de los fármacos , Fenoles/toxicidad , Análisis de Varianza , Animales , Glucemia/análisis , Metabolismo de los Hidratos de Carbono , Catalasa/metabolismo , Femenino , Transportador de Glucosa de Tipo 2/metabolismo , Homeostasis , Peróxido de Hidrógeno/metabolismo , Hiperinsulinismo/patología , Insulina/sangre , Peroxidación de Lípido/efectos de los fármacos , Hígado/enzimología , Hígado/fisiopatología , Tamaño de los Órganos/efectos de los fármacos , Páncreas/enzimología , Páncreas/fisiopatología , Fenoles/farmacocinética , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismoRESUMEN
Dioxins like 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) impair male reproductive system by increasing the generation of reactive oxygen species (ROS). Glucocorticoids have been found to suppress male reproductive function and also influence TCDD pathway. As stress is characterized by an increase in the level and activity of glucocorticoids, the present experiments were conducted to evaluate the effect of restraint stress on TCDD-induced testicular and epididymal toxicity. Adult male Wistar rats were subjected to either restraint stress (5 hours/day) or TCDD treatment (100 ng/kg b.w./day) or both for 15 days. Restraint stress or TCDD treatment raised the serum level of corticosterone and suppressed the testicular level of steroidogenic acute regulatory (StAR) protein and serum level of testosterone significantly. In the testis and epididymis, restraint stress or TCDD treatment raised the levels of lipid peroxidation and hydrogen peroxide and suppressed the activities of antioxidant enzymes significantly. In rats subjected to both restraint stress and TCDD treatment, a significant increase in the serum level of corticosterone and a significant decrease in the testicular level of StAR protein and serum level of testosterone were observed as compared to rats treated with TCDD alone. A significant increase in the levels of lipid peroxidation and hydrogen peroxide and a significant decrease in the activities of antioxidant enzymes were observed in the testis and epididymis of rats subjected to both restraint stress and TCDD treatment as compared to TCDD alone treated rats. Thus, restraint stress potentiates the adverse effects of TCDD on male reproductive organs.