Cypermethrin-induced Oxidative Stress Research Articles

Neuro-protective and redox potential of troxerutin against cypermethrin-induced neurotoxicity and oxidative stress in mice

The present study was designed to evaluate the protective efficacy of troxerutin against cypermethrin-induced behavioral defects, motor function abnormalities, and oxidative stress in mice. Twenty-four adult female albino mice were randomly divided into four equal groups. The first group served as control, the second group was treated with cypermethrin (20 mg/kg b.w) intraperitoneally at day 21, and the remaining two groups were orally supplemented with TRX (150, 300 mg/kg b.w) for 20 days and with cypermethrin (20 mg/kg b.w) intraperitoneally at day 21. Behavior activities recorded after cypermethrin exposure showed significantly impaired motor function (p≤0.05) as evidenced by the beam balance and pole test. The cypermethrin was also found to cause significant memory dysfunction. Moreover, the oxidative stress in terms of increased tissue malondialdehyde level (p≤0.05) was recorded in the cypermethrin group. The antioxidant activities of catalase and glutathione peroxidase were decreased (p≤0.05) after cypermethrin exposure. Troxerutin supplementation significantly improved the cypermethrin- -induced motor impairment and memory dysfunction. The supplementation of troxerutin significantly restored the redox status. Troxerutin attenuates the neurotoxic and behavioral deficits caused by cypermethrin. Furthermore, troxerutin also provides significant protection against cypermethrin-induced oxidative stress by improving the oxidative stress markers.

A Complex Interplay of DJ-1, LRRK2, and Nrf2 in the Regulation of Mitochondrial Function in Cypermethrin-Induced Parkinsonism.

Cypermethrin impairs mitochondrial function, induces redox imbalance, and leads to Parkinsonism in experimental animals. Knockdown of deglycase-1 (DJ-1) gene, which encodes a redox-sensitive antioxidant protein, aggravates cypermethrin-mediated α-synuclein overexpression and oxidative alteration of proteins. DJ-1 is also reported to be essential for maintaining stability of nuclear factor erythroid 2-related factor 2 (Nrf2), shielding cells against oxidative insult. Leucine-rich repeat kinase 2 (LRRK2), another protein associated with Parkinson's disease, is also involved in regulating mitochondrial function. However, underlying molecular mechanisms remain elusive. The study intended to explore an interaction of DJ-1, LRRK2, and Nrf2 in the regulation of mitochondrial function in cypermethrin-induced Parkinsonism. Small interfering RNA-mediated knockdown of DJ-1 and LRRK2 gene and pharmacological activation of Nrf2 were performed in rats and/or human neuroblastoma cells with or without cypermethrin. Indexes of oxidative stress, mitochondrial impairment, and Parkinsonism along with α-synuclein expression, post-translational modification, and aggregation were measured. DJ-1 gene knockdown exacerbated cypermethrin-induced increase in oxidative stress and intrinsic apoptosis and reduction in expression of mitochondrial antioxidant proteins via inhibiting nuclear translocation of Nrf2. Additionally, cypermethrin-induced oxidative stress, mitochondrial impairment, and α-synuclein expression and aggregation were found to be suppressed by LRRK2 gene knockdown, by promoting Nrf2 nuclear translocation and expression of mitochondrial antioxidant proteins. Furthermore, Nrf2 activator, sulforaphane, ameliorated cypermethrin-induced mitochondrial impairment and oxidative stress and provided protection against dopaminergic neuronal death. The findings indicate that DJ-1 and LRRK2 independently alter Nrf2-mediated changes and a complex interplay among DJ-1, LRRK2, and Nrf2 exists in the regulation of mitochondrial function in cypermethrin-induced Parkinsonism.

Proanthocyanidins regulate the Nrf2/ARE signaling pathway and protect neurons from cypermethrin-induced oxidative stress and apoptosis

Cypermethrin, a type II pyrethroid pesticide, is one of the most widely used pesticides in agricultural and in household settings. The toxic effects of cypermethrin are a matter of concern, as humans are almost inevitably exposed to it in daily life. It is an urgent problem to seek natural substances from plants that can eliminate or relieve the effects of pesticide residues on human health. Proanthocyanidins are the most potent antioxidants and free radical scavengers in natural plants, and are widely available in fruits, vegetables, and seeds. We found that proanthocyanidins (1, 2.5, and 5 μg/mL) can decrease ROS generation, relieve mitochondrial membrane potential loss, repair nuclear morphology, reduce cell apoptosis, and protect neurons from cypermethrin-induced oxidative insult. The protective mechanism exerted by proanthocyanidins against cypermethrin-induced neurotoxicity is negatively regulate rather than activate the Nrf2/ARE signaling pathway to maintain intracellular homeostasis.

Cypermethrin induces cell injury in primary cortical neurons of C57BL/6 mice by inhibiting Nrf2/ARE signaling pathway

To study the role of Nrf2/ARE signaling pathway in cypermethrin-induced oxidative stress and apoptosis of cerebral cortex neurons in C57BL/6 mice. The cortical neurons of C57BL/6 mice were cultured and identified, and a cypermethrin-induced cell injury model was established by treating the cells with 0, 25, 50 and 100 μmol/L of cypermethrin for 48 h. CCK-8 assay was used to analyze the effects of cypermethrin on the cell viability, and the fluorescence probe DCFH-DA was used for detecting intracellular reactive oxygen species (ROS); flow cytometry was performed for determining the apoptosis rate of the cells. The mRNA and protein expression levels of Nrf2 and its downstream genes HO-1 and NQO1 were detected using qPCR and Western blotting. Exposure to cypermethrin at different doses inhibited the viability of the cultured cortical neurons. With the increase of cypermethrin dose, the viability of the neurons decreased progressively, the intracellular ROS and the cell apoptosis rate increased, and the neuronal injury worsened. At the dose of 50 and 100 μmol/L, cypermethrin significantly down-regulated the expressions of HO-1, NQO1 and Nrf2 at both the mRNA and protein levels in the cells (P < 0.01). Cypermethrin exposure shows a dose-dependent neurotoxicity by inhibiting Nrf2/ARE signaling pathway, down-regulating the expression of Nrf2 and its downstream genes HO-1, NQO1 mRNA and protein, and inducing oxidative damage and apoptosis in primary mouse cortical neurons, .

Antiapoptotic effects of vitamins C and E against cypermethrin-induced oxidative stress and spermatogonial germ cell apoptosis.

Toxicological studies have demonstrated the relation between use of agrochemicals and fertility issues within males. Thus, the present study aimed to elucidate the propensity of cypermethrin (CYP) in bringing testicular germ cell apoptosis and effective attenuation by vitamins C and E in caprines. Reproductive toxicity of CYP was evaluated using histomorphological, cytological, and biochemical changes in the testicular germ cells in dose-dependent (1, 5, 10μg/mL) and time-dependent (4, 6, 8 h) manner. Histological and ethidium bromide/acridine orange fluorescence staining exhibited that vitamins C and E (0.5 and 1.0mM) successfully diminished the CYP-induced testicular germ cells apoptosis. CYP exposure along with vitamins C and E supplementation also resulted in significantly increased ferric reducing antioxidant power activity along with the antioxidant enzymes, namely catalase, superoxide dismutase, and glutathione-s-transferase, and decreased lipid peroxidation in testicular germ cells. Thus, vitamins C and E ameliorated CYP-induced testicular germ cell apoptosis, thereby preventing spermatogonial cells degeneration and male infertility.

Effects of ethanol extract of &lt;i&gt;Bersama engleriana&lt;/i&gt; leaves on oxidative stress and reproductive parameters in male Guinea pig (&lt;i&gt;Cavia porcellus&lt;/i&gt;) exposed to cypermethrin

Pesticides are used to improve agricultural yields; meanwhile they have detrimental effects on human and animal reproduction. This study aimed at evaluating the protective effects of ethanol extract of Bersama engleriana leaves against cypermethrin-induced oxidative stress and reproductive toxicity. Fifty male guinea pigs were divided into 5 groups (G1, G2, G3, G4 and G5) of 10 animals each. During 90 days, animals of G1 were given distilled water orally, while other groups received 137.50 mg/kg body weight (bw) of cypermethrin. In addition, G3, G4 and G5 received respectively 50, 100 and 200 mg/kg bw of ethanol extract of Bersama engleriana leaves. The testicular concentration of malondialdehyde, the activities of superoxide dismutase and catalase decreased significantly (P<0.05) in guinea pigs exposed to cypermethrin and ethanol extract of B. engleriana leaves compared with those exposed to cypermethrin only (G2), while the reverse effect was observed concerning the activity of peroxidases. The time of reaction of male guinea pig in the presence of females and the percentage of abnormal spermatozoa decreased significantly (P<0.05) in animals treated with the insecticide and the ethanol extract of B. engleriana leaves with respect to G2 animals. The weight of testes, the serum level of testosterone, the sperm count, mobility and the percentage of spermatozoa with normal plasma membrane increased significantly (P<0.05) in guinea pigs treated with ethanol extract of B. engleriana leaves compared with those submitted to cypermethrin only. The histological sections of testes in animals exposed to cypermethrin and ethanol extract of B. engleriana leaves showed a normal structure compared with those exposed to cypermethrin only, of which sections of testes revealed the presence of immature germinal cells in the seminiferous tubules lumen. Hence, ethanol extract of B. engleriana leaves prevent the induction of oxidative stress and reproductive parameters impairment by cypermethrin in male guinea pig. © 2017 International Formulae Group. All rights reserved. Keywords: Bersama engleriana , cypermethin, natural antioxidants, reproductive toxicity, sperm characteristics

Protective effect of Zizyphus lotus jujube fruits against cypermethrin-induced oxidative stress and neurotoxicity in mice

Context: Cypermethrin (CYP) is a synthetic pyrethroid insecticide used worldwide in agriculture, home pest control. The toxicity of CYP is well studied in many organisms.Objective: The aim of present study was to investigate the protective effect of Zizyphus lotus (Zizyp) fruit against neurotoxicity and oxidative stress induced by CYP in mice.Materials and methods: Mice were divided into four groups of six each: groups I and II were used as control and CYP control (20 mg/kg body weight). While, groups III was orally treated with Zizyphus lotus fruit (5 g/kg body weight) plus CYP (20 mg/kg body weight) for 18 days. Furthermore, HPLC–ESI–MS–MS (Q-Tof) and GC–MS were used to identify the compounds fraction.Results: Antioxidant enzyme catalase (CAT), neurotoxicity enzyme acetylcholinesterase (AChE) activities and hydrogen peroxide (H2O2), malondialdehyde (MDA) levels were determined in the liver, kidney and heart. CYP caused decreased CAT activity, inhibition of AChE activity and increased the levels of H2O2 and MDA in heart, liver and kidney.Conclusion: Our results indicate that Zizyp fruit is markedly effective in protecting mice against CYP-induced biochemical changes. This protection may be due to its antioxidant property and scavenging ability against active free radicals.

The protective effect of melatonin against cypermethrin-induced oxidative stress damage in Spodoptera litura (Lepidoptera: Noctuidae)

Antioxidant enzymes form the first-line defense against free radicals damage in organisms. Their regulation depends mainly on the oxidant and antioxidant status of the cell, given that oxidants are their principal modulators. Therefore, the aim of the present study was to investigate the effect of melatonin on synthetic pyrethroid insecticide-induced antioxidative enzymes activity in Spodoptera litura larvae. In addition, activities of enzymatic antioxidants viz. superoxide dismutase (SOD), glutathione S-transferase (GST), catalase (CAT), glutathione reductase (GR), α, β-esterase, and acetylcholine esterase (AChE) were assessed. There was no significant change in GST levels in the melatonin-treated groups. Melatonin modulates cypermethrin-induced changes in the activities of esterase and AChE, whereas SOD, CAT, and GR activity was significantly increased in melatonin-treated samples when compared to control. In conclusion, the results of the current study revealed that SP toxicity activated oxidant systems in all antioxidant systems in some tissues of insects. Melatonin administration led to a marked increase in antioxidant activity and inhibited GST and AChE in most of the tissues studied.

Protective Effect of Alpha-Lipoic Acid on Cypermethrin-Induced Oxidative Stress in Wistar Rats

Cypermethrin (CY), a class II pyrethroid pesticide, is globally used to control insects in the household and in agriculture. Despite beneficial roles, its uncontrolled and repetitive application leads to unintended effects in non-target organisms. In light of the relevant anti-oxidant properties of alpha-lipoic acid (ALA), in the work described herein we tested the effect of a commercially available ALA formulation on cypermethrin CY)-induced oxidative stress in Wistar rats. The rats were orally administered with 53.14 mg/kg of ALA and 35.71 mg/kg of CY for 60 days. The treatment with CY did not induce changes in either locomotor activities or in body weight. Differences were observed on superoxide dismutase (SOD), catalase (CAT) and lipid peroxidation that were re-established by ALA treatment at similar levels of the placebo group. Furthermore, ALA formulation increased glutathione (GSH) level and glutathione peroxidase (GPx) activity. Because of the widespread use of CY, higher amounts of pesticide residues are present in food, and a diet supplementation with ALA could be an active free radical scavenger protecting against diseases associated with oxidative stress.

Deleterious effects of cypermethrin on rat liver and kidney: Protective role of sesame oil

The involvement of reactive oxygen species (ROS) has been implicated in the toxicity of various pesticides. Our study was designed to investigate the induction of oxidative stress by cypermethrin; a Type II pyrethroid in rat liver and kidney. In addition, the protective role of sesame oil against the toxicity of cypermethrin was investigated. Animals were divided into four equal groups; the first group used as control while groups 2, 3 and 4 were treated with sesame oil (5 mL/kg b.w), cypermethrin (12 mg/kg b.w) and the combination of both sesame oil (5 mL/kg b.w) plus cypermethrin (12 mg/kg b.w), respectively. Rats were daily administered with their respective doses for 30 days by gavage. Repeated oral administration of cypermethrin was found to reduce the level of glutathione (GSH) and the activities of the antioxidant enzymes. While, the level of TBARS was elevated indicating the presence of oxidative stress. The activities of LDH, AST and ALT were decreased in the liver extract while increased in the plasma of the cypermethrin-treated group. Also, the levels of urea and creatinine were significantly increased after treatment with cypermethrin. Liver and kidney injury was confirmed by the histological changes. In conclusion, the administration of sesame oil provided significant protection against cypermethrin-induced oxidative stress, biochemical changes, histopathological damage and genomic DNA fragmentation.

Protective effect of curcumin on cypermethrin-induced oxidative stress in Wistar rats

The aim of present study was to investigate the protective effect of curcumin on cypermethrin-induced changes in blood biochemical markers and tissue antioxidant enzyme in rats. Rats were divided into six groups of six each: group I used as control and II and III groups were used as vehicle control. While, groups IV, V and VI were orally treated with curcumin (100 mg/kg body weight), cypermethrin (25 mg/kg body weight) and cypermethrin plus curcumin, respectively for 28 days. Serum biochemical markers were measured in the serum, and the levels of lipid peroxidation and antioxidant enzyme activity were determined in the liver, kidney and brain. Cypermethrin administration caused elevated level of blood biochemical markers in serum and lipid peroxidation in liver, kidney and brain. While the activities of non-enzymatic and enzymatic antioxidants levels were decreased except superoxide dismutase in liver, kidney and brain tissues. The presence of curcumin with cypermethrin significantly decreased the blood biochemical markers and lipid peroxidation but significantly increased the reduced glutathione, catalase and glutathione peroxidase level and preserved the normal histological architecture of the liver, kidney and brain. Our results indicate that curcumin can be potent protective agent against cypermethrin-induced biochemical alterations and oxidative damage in rats.

Effect of some socio-economic activities on fish diversity of lagoon systems in Ogun waterside Local Government of Ogun State, Nigeria

Cypermethrin, a Type II pyrethroid pesticide is commonly used in agriculture and many other domestic applications for pest control. Studies have shown that cypermethrin induces lipid peroxidation and alters the antioxidant status in non-target organisms. Fenugreek, a source of several polyphenols and flavonoids is a potent antioxidant. Hence in the present study we have investigated the possible effect of germinated fenugreek extract supplementation in counteracting the cypermethrin induced oxidative stress in erythrocytes of rats. Male Wistar rats were treated with 25 mg/kg weight (1/10 LD50) of cypermethrin and aqueous extract of germinated fenugreek (GFaq) (10%) for 60 days. Our results show that lipid peroxidation, an index of oxidative stress, significantly increased in circulation in cypermethrin-treated rats. The activities of SOD, CAT, GPx, GST in RBCs also decreased concomitantly in the cypermethrin treated rats. Treatment with aqueous extract of germinated fenugreek brought the values to near normal showing that fenugreek ameliorates cypermethrin-induced oxidative stress. HPLC analysis of the aqueous extract of germinated fenugreek showed the presence of flavonoids.© 2010 International Formulae Group. All rights reserved.Keywords: Cypermethrin, fenugreek, antioxidants, lipid peroxidation, oxidative stress, flavonoids

Protective role of L-ascorbic acid against cypermethrin-induced oxidative stress and lipid peroxidation in Wistar rats

Cypermethrin is a synthetic pyrethroid insecticide used for pest control in agriculture and as an acaricide in man and animals. This study was undertaken with the objective to investigate the propensity of cypermethrin to induce oxidative stress in rats following repetitive dermal exposure and its possible attenuation by L-ascorbic acid. Results obtained showed that cypermethrin significantly (p < 0.05) increased malonaldehyde levels, activity of catalase in rat erythrocytes and plasma protein levels. Whereas, activities of glutathione (GSH), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) were significantly (p < 0.05) reduced in the cypermethrin exposed rats as compared to the control. Supplementation of L-ascorbic acid in cypermethrin-exposed rats decreased lipid peroxidation of erythrocytes, total plasma protein and catalase activity significantly (p < 0.05) compared to non-cypermethrin-exposed group. However, L-ascorbic acid did not alleviate the negative effects of cypermethrin on the activities of SOD and GSH. This study revealed that the presence of L-ascorbic acid diminishes the adverse effects of cypermethrin on some oxidative stress parameters.

Cypermethrin-induced oxidative stress in rat brain and liver is prevented by Vitamin E or allopurinol

Considering that the involvement of reactive oxygen species (ROS) has been implicated in the toxicity of various pesticides, this study was designed to investigate the possibility of oxidative stress induction by cypermethrin, a Type II pyrethroid. Either single (170 mg/kg) or repeated (75 mg/kg per day for 5 days) oral administration of cypermethrin was found to produce significant oxidative stress in cerebral and hepatic tissues of rats, as was evident by the elevation of the level of thiobarbituric acid reactive substances (TBARS) in both tissues, either 4 or 24 h after treatment. Much higher changes were observed in liver, increasing from a level of 60% at 4 h up to nearly 4 times the control at 24 h for single dose. Reduced levels (up to 20%) of total glutathione (total GSH), and elevation of conjugated dienes (∼60% in liver by single dose at 4 h) also indicated the presence of an oxidative insult. Glutathione-S-transferase (GST) activity, however, did not differ from control values for any dose or at any time point in cerebral and hepatic tissues. Pretreatment of rats with allopurinol (100 mg/kg, ip) or Vitamin E (100 mg/kg per day, ig, for 3 days and a dose of 40 mg/kg on the 4th day) provided significant protection against the elevation of TBARS levels in cerebral and hepatic tissues, induced by single high dose of oral cypermethrin administration within 4 h. Thus, the results suggest that cypermethrin exposure of rats results in free radical-mediated tissue damage, as indicated by elevated cerebral and hepatic lipid peroxidation, which was prevented by allopurinol and Vitamin E.