Allethrin induced toxicity in the male reproductive tract of rats contributes to disruption in the transcription of genes involved in germ cell production

Madhubabu, Golla; Yenugu, Suresh

doi:10.1002/tox.21864

Cited by 12 publications

(13 citation statements)

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“…There was also a significant reduction in expression of antioxidant genes (CAT, GPx, SOD1, and CYP1B1) that was observed in the 100 mg/kg NP group. It has been reported that increased oxidative stress leads to antioxidant responses that involve modulation of the activity of antioxidant enzymes (Madhubabu and Yenugu, 2014), further supporting our findings. Of note, sperm cells as well as sperm plasma membrane contain very high proportions of polyunsaturated fatty acids (PUFA) (Yan et al, 2013).…”

Section: Discussionsupporting

confidence: 92%

4-Nonylphenol induces disruption of spermatogenesis associated with oxidative stress-related apoptosis by targeting p53-Bcl-2/Bax-Fas/FasL signaling

Duan

Butler

et al. 2016

Environ. Toxicol.

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4-Nonylphenol (NP) is a ubiquitous environmental chemical with estrogenic activity. Our aim was to test the hypothesis that pubertal exposure to NP leads to testicular dysfunction. Herein, 24 7-week-old rats were randomly divided into four groups and treated with NP (0, 25, 50, or 100 mg/kg body weight every 2 days for 20 consecutive days) by intraperitoneal injection. Compared to untreated controls, the parameters of sperm activation rate, curvilinear velocity, average path velocity, and swimming velocity were significantly lower at doses of 100 mg/kg, while sperm morphological abnormalities were higher, indicating functional disruption and reduced fertilization potential. High exposure to NP (100 mg/kg) resulted in disordered arrangement of spermatoblasts and reduction of spermatocytes in seminiferous tubules, while tissues exhibited a marked decline in testicular fructose content and serum FSH, LH, and testosterone levels. Oxidative stress was induced by NP (50 or 100 mg/kg) as evidenced by elevated MDA, decreased SOD and GSH-Px, and inhibited antioxidant gene expression (CAT, GPx, SOD1, and CYP1B1). In addition, NP treatment decreased proportions of Ki-67-positive cells and increased apoptosis in a dose-dependent manner. Rats treated with 100 mg/kg NP exhibited significantly increased mRNA expression of caspase-1, -2, -9, and -11, decreased caspase-8 and PCNA1 mRNA expression, downregulation of Bcl-2/Bax ratios and upregulation of Fas, FasL, and p53 at the protein and mRNA levels. Taken together, NP-induced apoptosis, hormonal deficiencies, and depletion of fructose potentially impairs spermatogenesis and sperm function. p53-independent Fas/FasL-Bax/Bcl-2 pathways may be involved in NP-induced oxidative stress-related apoptosis. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 739-753, 2017.

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Section: Discussionsupporting

confidence: 92%

4-Nonylphenol induces disruption of spermatogenesis associated with oxidative stress-related apoptosis by targeting p53-Bcl-2/Bax-Fas/FasL signaling

Duan

Butler

et al. 2016

Environ. Toxicol.

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“…We demonstrated that allethrin induces oxidative stress, apoptosis, and calcium release in testicular cells in vitro . Nasal or oral administration of allethrin‐induced oxidative stress and perturbed antioxidant enzyme levels in the male reproductive tract tissues . Further, allethrin toxicity resulted in downregulation of genes involved in sperm maturation and increased the phosphorylation of MAPK to favor tumor initiation .…”

Section: Introductionmentioning

confidence: 63%

“…We earlier reported that exposure of rats to allethrin‐based mosquito coil smoke caused lipid peroxidation and perturbation of antioxidant system in the male reproductive tract . Similar observations were also made when rats were orally exposed to allethrin . Since, the molecular mechanisms that may operate during allethrin toxicity responsible for reduced sperm production are not reported, using a rat model, we attempt to analyze the effect of oral administration of allethrin on genes that control spermatogenesis and steroidogenesis.…”

Section: Introductionmentioning

confidence: 99%

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Allethrin toxicity causes reproductive dysfunction in male rats

Madhubabu

Yenugu

2017

Environmental Toxicology

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Pyrethroids are widely used for domestic and agricultural purposes and their use is increasing, especially in developing countries. Uncontrolled use of these insecticides resulted in their entry into the food chain thereby causing toxicity to different organ systems. Allethrin is one of the widely used pyrethroids, but its toxicological effects are underreported when compared to other pyrethroids. Further, its effects on the male reproductive tract remain uncharacterized. In this study, its toxicity on the male reproductive tract was evaluated by administering 25-150 mg/kg body weight allethrin to adult rats for 60 days. The mRNA expression of factors that are important in spermatogenesis (Scf, c-Kit, Hsf2, Ovol1, Brdt, Kdm3A, Ybx-2, and Grth) and steroidogenesis (StAR, 3β-HSD, 17β-HSD) was significantly downregulated. Decreased levels of testosterone, reduced sperm count and daily sperm production was also observed due to allethrin toxicity. However, sperm quality parameters assessed by computer-assisted sperm analyzer were not affected. Spermatozoa obtained from allethrin-treated rats failed to undergo acrosome reaction. Results of this study indicate that allethrin affects spermatogenesis and sperm function, thus lending further support to the growing evidence of its toxicity.

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“…It has been demonstrated that allethrin (125 µM) induced apoptosis in testicular carcinoma cells (LC 450 ) 6 . The allethrin (5-100 µM) induced cell death in human corneal epithelial cells through mitochondrial dependent pathways of apoptosis 7 .…”

Section: Introductionmentioning

confidence: 99%

Prophylactic Role of Piperine and Curcumin in Allethrin Altered Hematological and Biochemical Parameters in Swiss Albino Mice

Kumar¹,

Divakar²,

Sasmal³

et al. 2015

Pharmacologia

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Background: Over the years, pyrethroids, including allethrin, are widely used for domestic and agricultural purposes and are found to be neurotoxic. However, effects on hematological and biochemical parametersare not elucidated. Thus, the first objective of the present study was to investigate the effect of allethrin on the hematological and biochemical parameters of Swiss albino mice. Further, for the amelioration of its effect, two different bioactive herbal extracts piperine (alkaloid) and curcumin (polyphenols) were evaluated. Methods: Animals were divided into six groups; the first group was used as a control. Groups 2, 3, 4, 5 and 6 were orally treated with allethrin (15 mg kgG .wt.), respectively for 28 days. Results: Administration of allethrin brought about a significant decrease in leukocytes, polymorphs, serum albumin, HDL, glucose and CPK and whereas, lymphocytes, haemoglobin, ALT, AST, serum creatinine, blood urea, total cholesterol, LDL, VLDL, triglycerides was found to be significantly increased following allethrin treatment. Gravimetric indices (body weight and organ weight) slightly declined following allethrin treatment. Further, the histopathological observations in allethrin treated mice showed the damage in all vital organs (kidney, liver, lungs, brain and heart) of Swiss albino mice. Administration of piperine and curcumin exhibited signi cant reversal of allethrin altered hematological and biochemical parameters. ALT, AST, serum creatinine, blood urea, serum albumin, HDL, glucose found to be comparable to that of the control group after piperine and curcumin administration. The presence of piperine and curcumin with allethrin preserved the normal histological architecture of the liver, kidney, lungs, brain and heart. Conclusion: These results indicate that piperine and curcumin can be a potent protective agent against allethrinalteredbiochemical and hematological alterations in mice.

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Allethrin induced toxicity in the male reproductive tract of rats contributes to disruption in the transcription of genes involved in germ cell production

Cited by 12 publications

References 55 publications

4-Nonylphenol induces disruption of spermatogenesis associated with oxidative stress-related apoptosis by targeting p53-Bcl-2/Bax-Fas/FasL signaling

4-Nonylphenol induces disruption of spermatogenesis associated with oxidative stress-related apoptosis by targeting p53-Bcl-2/Bax-Fas/FasL signaling

Allethrin toxicity causes reproductive dysfunction in male rats

Prophylactic Role of Piperine and Curcumin in Allethrin Altered Hematological and Biochemical Parameters in Swiss Albino Mice

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