Similar effects on the T and E2 levels were observed in male and female walking catfish Clarias batrachus exposed to herbicide pretilachlor Soni and Verma, Our findings of gonadal histology and sex steroids recommended that exposure to Harness ® reduced the capacity of gonadal resistance to oxidative stress and induced impaired gonadal growth.

In the present study, the lycopene-supplemented diet has a potential role in the alleviation of the reproductive damage induced by Harness ® exposure.

It showed the ability to attenuate the histological impairments of gonads and, to some extent, restore the control levels of T and E2. In this context, lycopene is defined as one of the utmost encouraging antioxidants contrary to reproductive toxicity Zhao et al.

Consistent with our results, lycopene amended the induced reproductive dysfunction by enhancing T and E2 levels, sperm features, and histological characteristics in African catfish Clarias gariepinus Sayed E.

Lycopene supplementation efficiency has also been demonstrated in humans and animals with favorable results of improvement in male infertility and an increase in sperm count and viability Durairajanayagam et al.

Lycopene might relieve the seminiferous tubule and spermatogenic cell injuries in mice Zhao et al. Lycopene also enhanced sperm motility, number, density, and testosterone levels in mice exposed to pollutants Boeira et al.

Lycopene also displayed an ability to ameliorate the ovarian histological disorders in rats Haq et al. In light of the present findings, it can be concluded that herbicide Harness ® acts as an endocrine disruptor in O.

niloticus ; it alters the thyroid, gonadal tissues and T3, T4, and reproductive steroid hormonal hemostasis through the stimulation of oxidative stress. The present study also indicated that lycopene supplementation worked as a potent antioxidant and was able to alleviate oxidative stress and thyroid and reproductive toxicity caused by herbicide Harness ® exposure.

The use of Harness ® in agriculture fields is a risk factor for the health and productivity of tilapia species as well as the health of human consumers; consequently, the usage of this herbicide in weed management demands to be considered cautiously. The data that support the findings of this study are available upon reasonable request.

The animal study was reviewed and approved by the Research Ethics Committee of the Molecular Biology Research and Studies Institute MBR , Assiut University, Assiut, Egypt.

Experimental design: RI and AHS. Experiment and analysis: RI, MH, and AHS. Data interpretation: RI, MH, and AHS. Writing and revision: RI and AHS. All authors contributed to the article and approved the Submitted version.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors, and the reviewers.

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Lin, C. Characterization, molecular modelling and developmental expression of zebrafish manganese superoxide dismutase. Fish shellfish Immunol. Linnewiel, K. Lubzens, E. Perhaps, due to the large oxidative-species-generating capacity of the brain, its limited antioxidative ability, and abundance of polyunsaturated fatty acids, the brain cells are susceptible to oxidative damage Oxidative stress is driven by ROS when the cells' ability to neutralize them is overwhelmed, or when the antioxidant system including enzymes such as catalase, and glutathione peroxidase is impaired PA overload causes over-activity of the respiratory chain and increases ROS production via Complexes III and IV, as well as uncoupling of ATP synthesis Our data shows that PA causes OS by significantly lowering the catalase and glutathione peroxidase activities Fig.

PA also caused a copious increase in the MDA level an index of lipid peroxidation coupled with abatement in GSH level in the brain of the untreated PA-challenged rats. The inhibition of catalase and glutathione peroxidase specific activities, following the PA challenge is consistent with the observations of Alnahdi et al.

Further, the activity of MPO was evaluated in the brain to substantiate other sources of ROS and inflammation following PA administration. Myeloperoxidase is produced by polymorphonuclear cells with pro-inflammatory and pro-oxidative functions. It is secreted by activated monocytes, microglia, and macrophages as a direct response to oxidative stress.

It also increases the production of pro-inflammatory cytokines 34 , The MPO in conjugation with hydrogen peroxide might cause the elevation of MDA and activate inflammation via the up-regulation of inducible nitric oxide synthase iNOS 34 , Upregulation of MPO following the PA challenge in this study, lends more credence to its ability to elicit cellular stress when taken in excess.

Nevertheless, lycopene administration essentially abated the occurrence of OS by normalizing the activities of CAT, GPx, and MPO as well as augmenting the level of GSH in the treated groups. Accordingly, the MDA level decreased meaningfully in the lycopene-treated rats when compared with the untreated group.

Consistent with earlier reports on the attenuation of OS indices in the hippocampus of diabetic rats 30 , our observations further substantiate the antioxidant effect of lycopene and its ability to inhibit lipid peroxidation, break the chain of ROS production, and induce antioxidant enzymes 16 , Excessive PA has putative detrimental effects on whole-body metabolism, especially de novo lipogenesis Indeed, disruption of PA homeostatic balance has been implicated in atherosclerosis and neurodegenerative disease 37 , Our data revealed a significant reduction in the brain phospholipids and cholesterol contents with a concomitant increase in TAG level in the PA untreated group Fig.

This trend suggests that PA might cause an imbalance in lipid metabolism in the brain. The mechanism behind these observations is unclear. Excessive PA is desaturated and incorporated into the cell membrane.

The desaturation process is necessary to maintain the concentration of phospholipids at the physiological range This disturbance might be responsible for the lowering of phospholipids levels observed in this study. The net result is disruption of TAG and cholesterol production.

As observed in this study, TAG level increased in the PA-untreated group, and TAG elevation is prodromal to inflammatory responses Lycopene has been shown to possess the ability to reduce intracellular lipids owning to its hypolipidemic effect Cholesterol level decreased in the PA control group relative to control in our study.

The underlying mechanism behind this observation is unclear. However, reduction of cholesterol level might limit the level of precursor for estrogen 2 E2 -a hormone produced by females, which is known to possess an anti-inflammatory effect by inhibiting the proliferation of TNF-α, IL-1β, and IL-6, while enhancing the synthesis of IL 41 , This observation might be responsible for the inflammatory responses exhibited by the PA group and might be another mechanism behind greater susceptibility to metabolic inflammation in females Nevertheless, treatment with lycopene reversed the PA-induced reduction in cholesterol level.

Neuroinflammation is driven by the master regulator of inflammation—NF-κB 43 via TLR4, which culminates into the secretion of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α 5. In this study, upregulation of the NF-κB -p65, parallels with concomitant increments in the expression of gene targets such as IL-1β, and IL-6 Fig.

Our observations are consistent with other studies 33 , 44 , wherein PA caused the upregulation of pro-inflammatory mediators.

Besides, upregulation of IL-1β in the CNS during HFD feeding might contribute to neuroinflammation and blood—brain-barrier BBB disruption IL relative expression, on the other hand, decrease in the PA control group, suggesting that PA overload might decrease the expression of anti-inflammatory cytokines, which may aggravate neuronal damage Nevertheless, our results showed normalization of IL level in the lycopene-treated groups suggesting its ability to enhance anti-inflammatory cytokine production.

Regardless of perturbations imposed on the inflammatory pathways by PA, lycopene essentially and abated inflammatory response in the groups treated with lycopene, especially the 0. This observation did not only authenticate the anti-inflammatory effect of lycopene but its neuroprotective effects 23 , 30 , perhaps due to its lipophilicity and ability to easily cross the blood—brain barrier to modulate cellular processes.

Disruption of biochemical processes often results in histological impairments and this represents the basis for tissue damage and loss of function In the present study, the brain of animals in the PA group showed severe vacuolation and excessive microglial population Fig.

Vacuolation in the brain cytoplasm is a degenerative feature arising from xenobiotic insult 47 and is mostly caused by damaged myelin sheath in the brain, suggesting that PA could initiate a complex yet unresolved process that induces demyelination of the CNS.

Groups treated with lycopene, however showed normal brain architecture when compared with the untreated group, thereby substantiating the neuroprotective role of lycopene against PA-induced neuroinflammation.

Conclusively, excessive PA intake caused the alteration of neuro-behavioural enzymes activities and induced OS by inhibiting the antioxidant system.

Furthermore, it might also cause dysregulation of lipid metabolism, as well as upregulation of the mRNA levels of pro-inflammatory cytokines.

Nevertheless, lycopene showed tremendous ameliorative effects of PA-induced neuroinflammation in rats. This is characterized by normalization of neurobehavioral enzymes, attenuation of OS indices, modulation of lipid metabolism, and abatement of inflammatory cytokines.

The conclusion is summarized as a graphics in Fig. Lycopene All- Trans and TRIzol were purchased from Solarbio Life Science and Co. Beijing, China. Louis, Missouri, United States.

All other chemicals used were of pure and analytical grade. The relative expressions of mRNA coding for IL-1β, IL-6, IL, NF-κB -p65 and GAPDH were quantified using the primer sequences synthesized by ShineGene Bio-Technologies, Inc.

Shanghai, Xuhui District China. Total cholesterol, triacylglycerol and phospholipids kits were sourced from Labkits® Diagnostics Company Barcelona, Spain. Thirty 30 female Wistar rats 8 weeks of age were purchased and kept in the Animal Housing Unit of the Department of Biochemistry, Federal University of Agriculture, Abeokuta FUNAAB , Ogun State, Nigeria.

The animals were acclimatized for two weeks before the commencement of the experiment. They were housed in plastic cages with good ventilation and supplied with standard pellets and clean water ad libitum. All animals were handled humanely according to the guidelines for use of experimental animals, and the study conformed to the Animal Research: Reports of In vivo Experiments ARRIVE guidelines for use of experimental animals Ethical approval FUNABCH was obtained for the study from the Ethical Committee of the Department of Biochemistry, FUNAAB.

Neuroinflammation was induced via administration of 5 mM PA intraperitoneally i. for five weeks. The ratio of PA to BSA was After the first five weeks, animals were grouped and treated as shown in Table 1 without halting PA administration together with the lycopene treatment , for two weeks.

The total study duration was for seven weeks. The lycopene was reconstituted in Olive oil and administered to the animal via oral gavage. The Acetylcholine esterase AchE activity was determined as briefly described.

A working reagent 2 mL total volume , containing 0. The method is based on the formation of the yellow anion- 5, 5-dithiol-bis-acid-nitrobenzoic, measured by absorbance at nm for 3 min.

The reaction was initiated by the addition of 0. Monoamine oxidase-A MAO-A activity was estimated using benzyl-amine as the substrate Briefly, the reaction mixture µL containing 0.

Finally, the supernatant was diluted five times with 1 M NaOH, and the absorbance read at nm. Adenosine deaminase ADA activity was assayed, as a direct measurement of the formation of ammonia produced when adenosine deaminase reacts with an excess of adenosine Concisely, 50 µL of the sample was reacted with 21 mM of buffered adenosine; pH 6.

Nucleotide triphosphatase NTPDase activity was determined in the brain homogenate by NTPDase enzymatic assay as described by Schetinger et al. A reaction medium containing 5 mM KCl, 1. The reaction was initiated by the addition of 10 µL of ATP 1.

Briefly, µL of diluted 1. The whole reaction mixture was thoroughly mixed, and the absorbance measured at nm against blank within 30 min.

The activity of NTPDase in the sample was extrapolated from the phosphate standard curve. Briefly, 70 μL of assay buffer containing Afterwards, samples 10 μL was added, vortexed thoroughly and incubated at 37 °C for 45 min. The superoxide dismutase SOD activity was based on the inhibition of the auto-oxidation of pyrogallol according to Marklund and Marklund Briefly, 20 µL of the sample was allowed to incubate with µL of mM Tris—HCl buffer, pH 8.

Then, 50 µL of 10 mM pyrogallol was added to initiate the reaction, monitored for 3 min at nm. Briefly, 0. In short, 25 µL of the homogenate was added to 75 µL GPx working reagent containing 4 mM GSH, 10 mM NaN3, 2.

The absorbance was taken 10 min later at nm. Myeloperoxidase MPO activity was assayed for in the post-nuclear fraction of the brain tissue as described by Klebanoff et al. Briefly, 10µL of the homogenate was reacted with 10 µL of 4 M guaiacol and mM H 2 O 2 in 0.

The lipid peroxidation MDA level was determined by measuring the formation of thiobarbituric acid reactive substances TBARS , according to the method of Buege and Aust The tube was immediately placed on ice to cool, centrifuged at rpm for 10 min and the absorbance of clear supernatant measured against blank at nm.

Reduced glutathione GSH level was assayed according to Ellman 61 method. Then, the homogenate was centrifuged at rpm for 10 min. Brain triacylglycerol TAG , cholesterol CHOL , and phospholipids PHOL were evaluated after the lipid was extracted from the brain tissue as described previously 62 using the commercial test kits.

The chloroform layer µL was then transferred into another Eppendorf tube, dried on a water bath at 60 °C. Triton-X 10 µL was added to the extract to precipitate any protein and dried again. The lipid content TAG, CHOL, and PHOL was then estimated with the test kits according to the manuals.

Brain total mRNA was extracted in the TRIzol, The mRNA was converted to cDNA, and amplified using EasyScript one-time RT PCR Supermix Cat No: AE , produced by TransGen Biotech Co. The relative expression was normalised against GAPDH. Primer sequences for the target genes are shown in Table 2. All these analyses were done using Statistical Package for Social Sciences SPSS version 20 IBM SPSS Software, United Kingdom The band densities of the gene expression analyses were quantified using Image-J, while all the graphs were plotted using Graph Pad Prism version 6 San Diego, CA 92, Tomassoni, D.

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Abstract Background: Infertility is a major worldwide problem which is caused by several factors such as environmental, physiological, and genetic conditions.