ABSTRACT
@#Objective To investigate the effect of acute exposure to cadmium combined with bacitracin on the endoplasmic reticulum stress (ERS) in testes and ovaries of rats and its regulation by nuclear factor erythroid-2-related factor 2 (Nrf2). Methods According to the 4×2 factorial design model, 48 specific pathogen free adult SD rats were divided into four groups: the control group and the low-, medium- and high- dose cadmium chloride exposure groups. Each group was further divided into with- or without bacitracin combined subgroup. There were six rats in each subgroup with 3 males and 3 females. The low-, medium- and high- dose groups were intraperitoneally injected with 5, 10, 20 mg/kg body weight of cadmium chloride solution, respectively. The control group was intraperitoneally injected with the same amount of 0.9% sodium chloride solution. Among them, rats in the bacitracin combined subgroup were given a one-time intraperitoneal injection of bacitracin at a dose of 20 mg/kg body weight two hours before cadmium chloride exposure. After 48 hours, the rats were sacrificed. The mRNA expression of glucose regulated protein78 kD (Grp78), protein kinase R-like endoplasmic reticulum kinase (Perk), Nrf2 in testes and ovaries of rats was determined using quantitative real-time polymerase chain reaction. The protein expression of GRP78, PERK, NRF2 was determined using Western blotting. Results The mRNA expression of Grp78, Perk, Nrf2 and the protein expression of GRP78, PERK, NRF2 in testes and ovaries of rats in the no bacitracin combined subgroups of the three dose groups showed different degrees of up-regulated changes compared with the no bacitracin combined subgroup of the control group (all P<0.05). Among them, the expression of the three kinds of mRNAs and proteins in the testes and ovaries of rats in the no bacitracin combined subgroups of the high-dose group was up-regulated (all P<0.05), and most of them were higher than those in the no bacitracin combined subgroups of the low- and medium-dose groups (all P<0.05). The expression of most of the three kinds of mRNAs and proteins in testes of rats showed different degrees of down-regulated changes (all P<0.05), but the expression of the three kinds of mRNAs and proteins showed different degrees of up-regulated changes in ovaries (all P<0.05) in the bacitracin combined subgroups of the three doses groups than that in the bacitracin combined subgroups of the control group, and especially in the bacitracin combined subgroups of the high-dose subgroup. The expression of the three kinds of mRNAs and proteins in testes and ovaries of rats in the bacitracin combined subgroups of the three doses groups showed different degrees of changes (all P<0.05) compared with the no bacitracin combined subgroup in the same group, and the expression in the bacitracin combined subgroups of the medium- and high-dose groups showed mainly down-regulated changes (all P<0.05). Conclusion Acute exposure to cadmium can induce different degrees of ERS, activate PERK/NRF2 signaling pathway, and improve the toxicity to testis and ovary. Bacitracin can inhibit cadmium-induced ERS, thereby inhibiting the activation of PERK/NRF2 signaling pathway, and enhancing the synergistic effect of cadmium on testis and ovary toxicity. The higher the exposure dose of cadmium, the more obvious the inhibitory effect.
ABSTRACT
The objective of this study was to evaluate the effect of short-term levosimendan exposure on oxidant/antioxidant status and trace element levels in the testes of rats under physiological conditions. Twenty male Wistar albino rats were randomly divided into two groups of 10 animals each. Group 1 was not exposed to levosimendan and served as control. Levosimendan (12 µg/kg) diluted in 10 mL 0.9% NaCl was administered intraperitoneally to group 2. Animals of both groups were sacrificed after 3 days and their testes were harvested for the determination of changes in tissue oxidant/antioxidant status and trace element levels. Tissue malondialdehyde (MDA) was significantly lower in the levosimendan group (P < 0.001) than in the untreated control group and superoxide dismutase and glutathione peroxidase (GSH-Px) levels were significantly higher in the levosimendan group (P < 0.001). Carbonic anhydrase, catalase and GSH levels were not significantly different from controls. Mg and Zn levels of testes were significantly higher (P < 0.001) and Co, Pb, Cd, Mn, and Cu were significantly lower (P < 0.001) in group 2 compared to group 1. Fe levels were similar for the two groups (P = 0.94). These results suggest that 3-day exposure to levosimendan induced a significant decrease in tissue MDA level, which is a lipid peroxidation product and an indicator of oxidative stress, and a significant increase in the activity of an important number of the enzymes that protect against oxidative stress in rat testes.
Subject(s)
Animals , Male , Rats , Antioxidants/pharmacology , Hydrazones/pharmacology , Malondialdehyde/metabolism , Oxidative Stress/drug effects , Pyridazines/pharmacology , Reactive Oxygen Species/metabolism , Trace Elements/analysis , Glutathione Peroxidase/metabolism , Random Allocation , Rats, Wistar , Superoxide Dismutase/metabolismABSTRACT
Cadmium (Cd), is an environmental and industrial pollutant that affects the male reproductive system. Cd induces its effect by affecting tissue antioxidant enzyme systems. Green tea extract (GTE) is an antioxidant and free radicals scavenger and has a chelating property. The purpose of this study was to investigate the protective effect of GTE against testes damage induced by Cd. Four groups of male rats, were utilized as following: Controls, GTE treated, Cd treated and Cd + GTE, treated rats at the same doses. The rats received GTE and or Cd orally in drinking water. After 5 weeks, the animals were sacrificed and testes were removed for microscopic and Biochemical evaluation. The levels of lipid peroxides (LPO) and glutathione (GSH) were detected in the tissue homogenates of rat testes. The current study showed marked morphological changes in the form of swelling, congestion, hemorrhage and necrosis in testes of rats treated with Cd alone. However, the rats treated with Cd+GTE showed milder edema, congestion and minute foci of necrosis in the testes. The LPO levels were significantly higher as compared to control and of GSH were significantly lower in Cd-treated rats but when GTE was co-administrated with Cd, there was an effective reduction in oxidative stress as shown by a significant rise of GSH level. In conclusion, the rats received GTE + Cd could enhance antioxidant/ detoxification system which consequently reduced the oxidative stress in rat testes. The beneficial effect of GTE is thus potentially reducing Cd toxicity and tissue damage.
El cadmio (Cd), es un contaminante del medio ambiente e industrial que afecta al sistema reproductivo masculino. Cd induce su efecto por afección de los sistemas enzimáticos antioxidantes de los tejidos. El extracto de té verde (ETV) es un antioxidante y buscador de radicales libres y tiene una propiedad quelante. El objetivo de este estudio fue investigar el efecto protector de ETV contra daños provocado por Cd a los testículos. Cuatro grupos de ratas macho, se utilizaron: Controles, tratados con ETV, tratados con Cd y tratados con Cd + ETV, todas las ratas tratadas con las mismas dosis. Las ratas recibieron ETV o Cd por vía oral en el agua potable. Después de 5 semanas, los animales fueron sacrificados y los testículos fueron retirados para la evaluación microscópica y bioquímica. Los niveles de peróxidos lípidos (LPO) y de glutation (GSH) fueron detectados en el tejido homogenizado de rata testículos. El estudio demostró marcados cambios morfológicos como inflamación, congestión, hemorragia y necrosis en los testículos de las ratas tratadas solamente con Cd. Sin embargo, las ratas tratadas con Cd + ETV mostraron leves signos de edema, congestión y focos de necrosis en los testículos. Los niveles de LPO fueron significativamente mayores en comparación con el control y la de GSH fue significativamente menor en las ratas tratadas con Cd, pero cuando ETV fue co-administrado con Cd, hubo una reducción efectiva en el estrés oxidativo, como lo demuestra el aumento significativo del nivel de GSH. En conclusión, las ratas recibieron GTE + Cd que podría aumentar el sistema antioxidante / desintoxicación, por tanto, reducir el estrés oxidativo en los testículos de ratas. El efecto beneficioso de GTE es reducir la toxicidad y el daño tisular causado Cd.