RESUMEN
The adverse health effects of benzene occupational and circumstance pollution exposure are an increasing concern. It leads to damage to various human tissues including bone marrow and ovarian tissues and many vital physiological processes. Previous studies showed that kefir is a rich probiotic, having protective effect, thanks to its antioxidant, anti-inflammatory, and immunomodulatory capacity. The purpose of this study was to evaluate the potential efficacy of kefir to remediate benzene toxicity in rat. Thirty-two female rats were randomly allocated and administered orally with benzene and/or kefir during a period of 21 consecutive days. At the end of the experiment, hematological and bone marrow cell changes were estimated. The animals exposed to benzene exhibited anemia and a significant decrease in the levels of white blood cell. Moreover, benzene led to the activation of gene expression of the pro-inflammatory cytokines interleukin-1ß (IL-1ß) and interleukin-6 (IL-6), a myelotoxicity in bone marrow cells. Our data showed that kefir treatment alleviated benzene-associated weight loss and increased the number of whole blood cells in peripheral blood and nucleated cells in the bone marrow. Furthermore, these physiological results were observed with animals showing high concentrations of lactic acid bacteria (LAB) determined from fecal samples, which are considered an indicator of kefir-associated microorganisms. Our study suggests that kefir is a potential nutritional supplement target to attenuate hematotoxicity induced by benzene.
Asunto(s)
Kéfir , Probióticos , Animales , Antioxidantes , Benceno/toxicidad , Femenino , Humanos , Leche , RatasRESUMEN
Curcumin is a molecule found in turmeric root that has anti-inflammatory, antioxidant, and anti-tumor properties and has been widely used as both an herbal drug and a food additive to treat or prevent neurodegenerative diseases. This study aimed to investigate the effect of curcumin on neurobehavioral and neuropathological alterations induced by acetamiprid on male rats. Three groups of ten male Wistar rats each were used for the study: the first was a control group (CTR) that did not consume acetamiprid (ACE); the second was an experimental group (ACE) that consumed 40 mg/kg body weight/day of acetamiprid; and the third group (CUR) received curcumin (100 mg/kg) and acetamiprid (40 mg/kg) in combination. Neurobehavioral evaluations including inclined plane performance and forepaw grip time were studied. Treatment with CUR significantly prevented ACE-treated rats from impairments in the performance of neurobehavioral tests, indicating the presence of deficits on sensorimotor and neuromuscular responses. In addition, Curcumin administration protects rats against acetamiprid-induced cerebellum toxicity such as increase in AChE and BChE activities, decrease on cells viability, oxidative stress, and an increase of intracellular calcium. Taken together, these results demonstrate for the first time that ACE treatment substantially impairs the survival of primary neuronal cells through the induction of necrosis concomitantly with the generation of an oxidative stress. Additionally, curcumin reduced histopathological changes caused by ACE.
Asunto(s)
Conducta Animal/efectos de los fármacos , Cerebelo/efectos de los fármacos , Curcumina/farmacología , Neonicotinoides/toxicidad , Fármacos Neuroprotectores/farmacología , Síndromes de Neurotoxicidad/prevención & control , Estrés Oxidativo/efectos de los fármacos , Animales , Cerebelo/crecimiento & desarrollo , Cerebelo/metabolismo , Masculino , Actividad Motora/efectos de los fármacos , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Síndromes de Neurotoxicidad/metabolismo , Síndromes de Neurotoxicidad/patología , Ratas , Ratas WistarRESUMEN
The immune system can be the target of many chemicals, with potentially severe adverse effects on the host's health. In the literature, carbamate (CM) pesticides have been implicated in the increasing prevalence of diseases associated with alterations of the immune response, such as hypersensitivity reactions, some autoimmune diseases and cancers. CMs may initiate, facilitate, or exacerbate pathological immune processes, resulting in immunotoxicity by induction of mutations in genes coding for immunoregulatory factors and modifying immune tolerance. In the present study, direct immunotoxicity, endocrine disruption and inhibition of esterases activities have been introduced as the main mechanisms of CMs-induced immune dysregulation. Moreover, the evidence on the relationship between CM pesticide exposure, dysregulation of the immune system and predisposition to different types of cancers, allergies, autoimmune and infectious diseases is criticized. In addition, in this review, we will discuss the relationship between immunotoxicity and cancer, and the advances made toward understanding the basis of cancer immune evasion.
Asunto(s)
Carbamatos/farmacología , Carcinógenos/farmacología , Sistema Inmunológico/efectos de los fármacos , Plaguicidas/farmacología , Animales , Humanos , Activación de Linfocitos , Linfocitos/efectos de los fármacos , Linfocitos/inmunologíaRESUMEN
N-acetylcysteine (NAC), a cysteine pro-drug and glutathione precursor has been used in therapeutic practices for several decades, as a mucolytic agent and for the treatment of numerous disorders including paracetamol intoxication. There is a growing interest concerning the beneficial effects of NAC against the early stages of toxicity-induced by pesticides. Nevertheless, the mechanisms underlying the therapeutic and clinical applications of NAC are not fully understood. In this review we aimed to focus on the protective effects of NAC against oxidative stress caused by pesticide in many organs. The possible mechanisms of action may be associated to its antioxidant properties. The anti-oxidative activity of NAC has been attributed to the fast reaction with free radicals as well as the restitution of reduced glutathione (GSH).
Asunto(s)
Acetilcisteína/farmacología , Acetilcisteína/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Profármacos/uso terapéutico , Animales , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Humanos , Modelos Biológicos , Profármacos/farmacologíaRESUMEN
Organophosphorus (OP) and carbamate (CM) pesticides are widely used in agriculture. These pesticides are highly toxic to humans and their residues in food pose potential threat to human health. In this comparative study, we investigated the effect of subchronic exposure of OPs (malathion, MAL) and CM (Carbosulfan, CB) on rat liver and spleen. Biochemical analysis showed that levels of hepatic enzymes (ALT, ALP, LDH and PAL) changed after exposure to the pesticides. In the liver extracts, lipid peroxidation index increased after the treatment by pesticides. Our results indicated that exposure to MAL and CB leads to alteration of liver redox status. Both pesticides induced focal inflammation and fibrosis in the liver. After subchronic administration of MAL (200 mg/kg) and CB (25 mg/kg), systemic inflammation, as depicted by the increase in IFN-δ activity in liver, was observed in both malathion and carbosulfan treated animals. In addition, the results showed that MAL significantly increased TCD4+ and TCD8+ lymphocyte number. It also decreased INF-δ and IL-4 production. However, CB induced a reduction of TCD8+ number and cytokine production in spleen cells. In conclusion, malathion and carbosulfan had significant immunomodulatory properties in the spleen with inflammation and oxidative stress induction in the liver.
Asunto(s)
Carbamatos/farmacología , Peroxidación de Lípido/efectos de los fármacos , Malatión/farmacología , Animales , Catalasa/metabolismo , Glutatión Peroxidasa/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratas , Ratas Wistar , Bazo/efectos de los fármacos , Bazo/metabolismo , Superóxido Dismutasa/metabolismoRESUMEN
Imidacloprid is the most important example of the neonicotinoid insecticides known to target the nicotinic acetylcholine receptor in insects, and potentially in mammals. N-Acetyl-l-cysteine (NAC) has been shown to possess curative effects in experimental and clinical investigations. The present study was designed to evaluate the recovery effect of NAC against Imidacloprid-induced oxidative stress and cholinergic transmission alteration in hypothalamic-pituitary-adrenal (HPA) axis of male rats following subchronic exposure. About 40 mg/kg of Imidacloprid was administered daily by intragastric intubation and 28 days later, the rats were sacrificed and HPA axis tissues were removed for different analyses. Imidacloprid increased adrenal relative weight and cholesterol level indicating an adaptive stage of the general alarm reaction to stress. Moreover, Imidacloprid caused a significant increase in malondialdehyde level, the antioxidants catalase, superoxide dismutase and glutathione-S-transferase showed various alterations following administration and significant depleted thiols content was only recorded in hypothalamic tissue. Furthermore, the hypothalamic and pituitary acetylcholinesterase activity and calcium level were significantly increased highlighting the alteration of cholinergic activity. The present findings revealed that HPA axis is a sensitive target to Imidacloprid (IMI). Interestingly, the use of NAC for only 7 days post-exposure to IMI showed a partial therapeutic effect against Imidacloprid toxicity.
Asunto(s)
Acetilcisteína/aislamiento & purificación , Sistema Hipotálamo-Hipofisario/lesiones , Imidazoles/toxicidad , Insecticidas/toxicidad , Nitrocompuestos/toxicidad , Sistema Hipófiso-Suprarrenal/lesiones , Acetilcisteína/metabolismo , Glándulas Suprarrenales/patología , Animales , Antioxidantes/metabolismo , Calcio/metabolismo , Colesterol/sangre , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Sistema Hipotálamo-Hipofisario/metabolismo , Masculino , Neonicotinoides , Tamaño de los Órganos , Estrés Oxidativo/efectos de los fármacos , Sistema Nervioso Parasimpático/efectos de los fármacos , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Sistema Hipófiso-Suprarrenal/metabolismo , Ratas , Ratas Wistar , Transmisión Sináptica/efectos de los fármacosRESUMEN
OBJECTIVE: N-acetylcysteine (NAC), a cysteine pro-drug and glutathione precursor has been used in therapeutic practices for several decades, as a mucolytic agent and for the treatment of numerous disorders including paracetamol intoxication. There is a growing interest concerning the beneficial effects of NAC against the early stages of type-2 diabetes development. Nevertheless, the mechanisms underlying the therapeutic and clinical applications of NAC are not fully understood. In this review we aimed to focus on the protective effects of NAC against insulin resistance. DESIGN AND METHODS: The possible mechanisms of action were reviewed using the major findings of more than 100 papers relating to the antioxidant, anti-inflammatory and anti-apoptotic properties of NAC. RESULTS: The anti-oxidative activity of NAC has been attributed to its fast reactions with free radicals as well as the restitution of reduced glutathione. Further, NAC has anti-inflammatory and anti-apoptotic properties which can have positive effects during the inflammatory process in insulin resistance. Moreover, NAC can modulate certain signaling pathways in both insulin target cells and ß cells. CONCLUSIONS: The diverse biological effects of NAC may make it a potential adjuvant or therapeutic target in the treatment of type-2 diabetes. So, further studies are required for determining its ability to alleviate insulin resistance and to improve insulin sensitivity.
Asunto(s)
Acetilcisteína/farmacología , Diabetes Mellitus Tipo 2/prevención & control , Resistencia a la Insulina/fisiología , Animales , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , HumanosRESUMEN
Organophosphorus pesticides are known to disturb glucose homeostasis and increase incidence of metabolic disorders and diabetes via insulin resistance. The current study investigates the influence of malathion on insulin signaling pathways and the protective effects of N-acetylcysteine (NAC). Malathion (200 mg/kg) and NAC (2 g/l) were administered orally to rats, during 28 consecutive days. Malathion increases plasma glucose, plasma insulin and glycated hemoglobin levels. Further, we observed an increase of insulin resistance biomarkers and a decrease of insulin sensitivity indices. The GP, GSK3ß and PEPCK mRNA expressions were amplified by malathion while, the expression of glucokinase gene is down-regulated. On the basis of biochemical and molecular findings, it is concluded that malathion impairs glucose homeostasis through insulin resistance and insulin signaling pathways disruptions in a way to result in a reduced function of insulin into hepatocytes. Otherwise, when malathion-treated rats were compared to NAC supplemented rats, fasting glucose and insulin levels, as well as insulin resistance indices were reduced. Furthermore, NAC restored liver GP and PEPCK expression. N-acetylcysteine showed therapeutic effects against malathion-induced insulin signaling pathways disruption in liver. These data support the concept that antioxidant therapies attenuate insulin resistance and ameliorate insulin sensitivity.
Asunto(s)
Acetilcisteína/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Glucosa/metabolismo , Resistencia a la Insulina , Insulina/metabolismo , Hígado/metabolismo , Malatión/farmacología , Animales , Antioxidantes/metabolismo , Biomarcadores/análisis , Inhibidores de la Colinesterasa/farmacología , Depuradores de Radicales Libres/farmacología , Glicerol Quinasa/metabolismo , Glucógeno Sintasa Quinasa 3/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Hígado/efectos de los fármacos , Masculino , Estrés Oxidativo/efectos de los fármacos , Fosfoenolpiruvato Carboxiquinasa (GTP)/metabolismo , Ratas , Ratas Wistar , Transducción de Señal/efectos de los fármacosRESUMEN
Several studies showed that organophosphorus pesticides disturb glucose homeostasis and can increase incidence of metabolic disorders and diabetes via insulin resistance. The current study investigates the influence of malathion on glucose metabolism regulation, in vivo, during subchronic exposure. Malathion was administered orally (200 mg/kg), once a day for 28 consecutive days. Plasma glucose, insulin and Glycated hemoglobin levels were significantly increased while hepatic glycogen content was decreased in intoxicated animals compared with the control group. Furthermore, there was a significant disturbance of lipid content in subchronic treated and post-treated rats deprived of malathion for one month. In addition, we used the homeostasis model assessment (HOMA) to assess insulin resistance (HOMA-IR) and pancreatic ß-cell function (HOMA-ß). Our results show that malathion increases insulin resistance biomarkers and decreases insulin sensitivity indices. Statistical analysis demonstrates that there was a positive and strong significant correlation between insulin level and insulin resistance indices, HOMA-IR, HOMA-ß. Similarly, a negative and significant correlation was also found between insulin level and insulin sensitivity indices. For the first time, we demonstrate that malathion induces insulin resistance in vivo using homeostasis model assessment and these changes were detectable one month after the end of exposure. To explain insulin resistance induced by malathion we focus on lipid metabolism disturbances and their interaction with many proteins involved in insulin signaling pathways.
Asunto(s)
Resistencia a la Insulina , Insulina/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Malatión/toxicidad , Animales , Glucemia/efectos de los fármacos , Hemoglobina Glucada/metabolismo , Insecticidas/toxicidad , Células Secretoras de Insulina/efectos de los fármacos , Células Secretoras de Insulina/metabolismo , Masculino , Ratas , Ratas WistarRESUMEN
Insulin resistance and risk of type 2 diabetes are the most important complications following exposure to organophosphorous (OPs) pesticides. Regarding the importance of liver on metabolic pathways regulation, in particular blood glucose homeostasis, we focused on liver inflammation and oxidative damages in a subchronic model of toxicity by malathion. Adult male Wistar rats of body weight 200-250g were used for the study. Malathion (200mg/kg b.w./day) was administered to rats by oral intubation for 28 days. Glycemic and insulin resistance indices, markers of liver injury, markers of inflammation and oxidative stress were assessed. Malathion-treated rats showed increased glycemia, insulinemia and glycated hemoglobin level, HOMA-IR and HOMA-ß indices, plasma activities of hepatocellular enzymes, lipid peroxidation index, CD3(+)/CD4(+) and CD3(+)/CD4(+) and pro-inflammatory cytokines when decreased antioxidant status in liver was noted. Most of our study indicates that malathion promotes insulin resistance, inflammation and Hepatosteatosis in subchronic model of exposure. On the basis of biochemical and molecular findings, it is concluded that insulin resistance induced by malathion occurs through oxidative stress and related pro-inflammatory markers in a way to result in a reduced function of insulin in liver cells.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/inmunología , Hígado Graso/inmunología , Inflamación/inducido químicamente , Resistencia a la Insulina , Malatión/toxicidad , Estrés Oxidativo/efectos de los fármacos , Plaguicidas/toxicidad , Animales , Biomarcadores/sangre , Glucemia/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Citocinas/inmunología , Citocinas/metabolismo , Hígado Graso/inducido químicamente , Hígado Graso/patología , Regulación de la Expresión Génica/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Masculino , Dosis Máxima Tolerada , Ratas , Ratas WistarRESUMEN
The present study was designed to determine the immunosuppressive effects of carbosulfan (CB) and their relationship with an increased formation of reactive oxygen species in rat. Further, we aimed to evaluate the protective effects of N-acetyl-cysteine (NAC) against immunopathological changes induced by CB. Carbosulfan (25 mg/kg) and NAC (2 g/l) were given daily to rats during 30 days, via oral gavage and drinking water, respectively. Cell-mediated immune function, cytokines production, biomarkers of cell redox state maintenance, lipid peroxidation and the activities of antioxidant enzymes were measured in the spleen. Our data showed an increase in WBC percent (28.42%), a reduction in spleen CD8 T-lymphocytes (-85.63%) and a decrease in immunosuppressive cytokines production such as INF-gamma and IL-4. There was a switch from Th1-type to Th2-type cytokines with an unbalance toward anti-inflammatory cytokines. Moreover, a significant decrease in reduced glutathione (-71.68%) and total thiols (-39.81%) levels were observed in treated rats. Conversely, malondialdehyde level in spleen was increased (-42.3%), while glutathione-S-transferase, glutathione peroxidase, superoxide dismutase and catalase activities were depleted. Our results suggest that subchronic CB administration affects cellular enzyme and non-enzyme-mediated antioxidant defense systems and promotes immunotoxicity in rat. On the other hand, our data showed protective effects of NAC. Indeed, there was a recovery of oxidative stress markers and cytokines production. The use of NAC, in our study, as a therapeutic agent showed interesting results against CB toxicity.
Asunto(s)
Acetilcisteína/farmacología , Carbamatos/administración & dosificación , Carbamatos/toxicidad , Inmunomodulación/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Bazo/efectos de los fármacos , Acetilcisteína/administración & dosificación , Animales , Antioxidantes/administración & dosificación , Antioxidantes/farmacología , Esquema de Medicación , Peroxidación de Lípido , Masculino , Plaguicidas/toxicidad , Distribución Aleatoria , Ratas , Ratas WistarRESUMEN
Malathion toxicity has been related to the inhibition of acetylcholinesterase, induction of oxidative stress, liver damage and impairment of kidney function as well as hematotoxicity. N-acetyl-l-cysteine (NAC) has been shown to possess curative effects in experimental and clinical investigations. The present study was designed to evaluate the protective effect of NAC against toxic consequences of malathion exposure in Wistar rats. Malathion was given daily to rats via oral gavage and NAC in drinking water during seven days. When malathion-treated rats were compared with control, a leukocytosis and reduced hemoglobin (HGB) content were detected. Furthermore, malathion produced a significant increase in liver enzymes such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase and creatinine kinase. In addition, a decrease in acid phosphatase activity, protein and globulin levels were observed in malathion-treated rats compared with control. Moreover, analyses of the mineral status showed a disturbance in calcium, magnesium, phosphore and iron contents of the malathion-treated rats. Interestingly, NAC showed therapeutic effects against malathion toxicity. Indeed, HGB content and all liver enzymes were restored to normal values. Finally, the use of NAC as therapeutic agent for only seven days during malathion exposure showed interesting results on tissues damages.
Asunto(s)
Acetilcisteína/farmacología , Insecticidas/toxicidad , Malatión/toxicidad , Alanina Transaminasa/metabolismo , Fosfatasa Alcalina/metabolismo , Animales , Aspartato Aminotransferasas/metabolismo , Colinesterasas/metabolismo , Creatina Quinasa/metabolismo , Pruebas de Función Renal , L-Lactato Deshidrogenasa/metabolismo , Hígado/efectos de los fármacos , Hígado/enzimología , Masculino , Ratas , Ratas WistarRESUMEN
AIMS: Occupational exposure to organophosphate pesticides is becoming a common and increasingly alarming world-wide phenomenon. The present study is designed to investigate the preventive effect of N-acetylcysteine on malathion-induced hepatic injury and inflammation in rats. MAIN METHODS: Adult male Wistar rats of body weight 200-230 g were used for the study. Malathion (200mg/kg b.w./day) was administered to rats by oral intubation and N-acetylcysteine (2g/l) in drinking water for 28 days. Rats were sacrificed on the 28th day, 2h after the last administration. Markers of liver injury (aspartate transaminase, alanine transaminase, alkaline phosphatase and lactate desyhdogenase), inflammation (leukocyte counts, myeloperoxidase, immunophenotyping of CD4(+) and CD8(+), interleukin-1ß, interleukin-6 and interferon-γ expression) and oxidative stress (lipid peroxidation, reduced glutathione and antioxidant status) were assessed. KEY FINDINGS: Malathion induced an increase in activities of hepatocellular enzymes in plasma, lipid peroxidation index, CD3(+)/CD4(+) and CD3(+)/CD4(+) percent and pro-inflammatory cytokines, when decreased antioxidant status in liver was noted. When malathion-treated rats were compared to NAC supplemented rats, leukocytosis, T cell count and IL-1ß, IL-6, INF-γ expression were reduced. Furthermore, NAC restored liver enzyme activities and oxidative stress markers. SIGNIFICANCE: Malathion induces hepatotoxicity, oxidative stress and liver inflammation. N-acetylcysteine showed therapeutic effects against malathion toxicity.
Asunto(s)
Acetilcisteína/farmacología , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Insecticidas/toxicidad , Malatión/toxicidad , Animales , Apoptosis/efectos de los fármacos , Biomarcadores/análisis , Western Blotting , Proliferación Celular/efectos de los fármacos , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Citocinas/metabolismo , Citometría de Flujo , Depuradores de Radicales Libres/farmacología , Inflamación/inducido químicamente , Inflamación/inmunología , Leucocitos/efectos de los fármacos , Leucocitos/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Linfocitos/efectos de los fármacos , Linfocitos/metabolismo , Masculino , Estrés Oxidativo/efectos de los fármacos , Peroxidasa/metabolismo , ARN Mensajero/genética , Ratas , Ratas Wistar , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
There is increasing evidence reporting that organophosphorus pesticides (OPs) impair glucose homeostasis and cause insulin resistance and type 2 diabetes. Insulin resistance is a complex metabolic disorder that defies explanation by a single etiological pathway. Formation of advanced glycation end products, accumulation of lipid metabolites, activation of inflammatory pathways and oxidative stress have all been implicated in the pathogenesis of insulin resistance. Ultimately, these molecular processes activate a series of stress pathways involving a family of serine kinases, which in turn have a negative effect on insulin signaling. Experimental and clinical data suggest an association between these molecular mechanisms and OPs compounds. It was first reported that OPs induce hyperglycemia. Then a concomitant increase of blood glucose and insulin was pointed out. For some years only, we have begun to understand that OPs promote insulin resistance and increase the risk of type 2 diabetes. Overall, this review outlines various mechanisms that lead to the development of insulin resistance by OPs exposure.