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Cumulative Effects of Paraoxon and Leptin on Oxidative Damages in Rat Tissues: Prophylactic and Therapeutic Roles of N-Acetylcysteine

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Abstract

Exposure to paraoxon (POX) and leptin (LP) could cause an imbalance between oxidants and antioxidants in an organism, which can be prevented by introduction of exogenous antioxidants such as N-acetylcysteine (NAC). The aim of this study was to evaluate synergic or additive effects of administration of exogenous LP plus POX on the antioxidant status, as well as the prophylactic and therapeutic roles of NAC in various rat tissues. Fifty-four male Wistar rats were divided into nine groups treated with different compounds: Control (no treatment), POX (0.7 mg/kg), NAC (160 mg/kg), LP (1 mg/kg), POX+LP, NAC-POX, POX-NAC, NAC-POX+LP, and POX+LP-NAC. In the last five groups, only the order of administered compounds differed. After 24 h, plasma and tissues were sampled and examined. The results showed that administration of POX plus LP significantly increased biochemical indices in plasma and antioxidant enzymes activities and decreased glutathione content in the liver, erythrocytes, brain, kidney, and heart. In addition, cholinesterase and paraoxonase 1 activities in the POX+LP-treated group were decreased and malondialdehyde level was increased in the liver, erythrocytes, and brain. However, administration of NAC rectified induced changes although not to the same extent. Our study suggests that POX or LP administration engage the oxidative stress system per se; however, their combination did not produce significantly greater effects. Moreover, both prophylactic and therapeutic treatments of rats with NAC supported the antioxidant defense against oxidative damage in tissues, most probably through both its free radical scavenging ability and maintaining intracellular GSH levels. It can therefore be suggested that NAC has particularly protective effects against POX or/and LP toxicity.

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Abbreviations

ALP:

alkaline phosphatase

ALT:

alanine transaminase

AST:

aspartate transaminase

CAT:

catalase

GSH:

reduced glutathione

GST:

glutathione S-transferase

IL-1:

interleukin-1

IL-6:

interleukin-6

LDL-L:

low-density lipoprotein-cholesterol

LP:

leptin

MDA:

malondialdehyde

NAC:

N-acetyl-L-cysteine

OP:

organophosphorus pesticides

PON1:

paraoxonase 1

POX:

paraoxon

ROS:

reactive oxygen species

SOD:

superoxide dismutase

References

  1. Jalili, C., Farzaei, M. H., Roshankhah, S., and Salahshoor, M. R. (2019) Resveratrol attenuates malathion-induced liver damage by reducing oxidative stress, J. Lab. Physicians, 11, 212-219, https://doi.org/10.4103/JLP.JLP_43_19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Imam, A., Sulaiman, N. A., Oyewole, A. L., Chengetanai, S., Williams, V., Ajibola, M. I., Folarin, R. O., Muhammad, A. U. S., Shittu, S.-T. T., and Ajao, M. S. (2018) Chlorpyrifos-and dichlorvos-induced oxidative and neurogenic damage elicits neuro-cognitive deficits and increases anxiety-like behavior in wild-type rats, Toxics, 6, 71, https://doi.org/10.3390/toxics6040071.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Zare, Z., Tehrani, M., Zarbakhsh, S., Farzadmanesh, H., Shafia, S., Abedinzade, M., Ghanaat, A., and Mohammadi, M. (2020) Effects of paraoxon exposure on expression of apoptosis-related genes, neuronal survival, and astrocyte activation in rat prefrontal cortex, Neurotox. Res., 37, 356-365, https://doi.org/10.1007/s12640-019-00106-x.

    Article  CAS  PubMed  Google Scholar 

  4. Faro, L., Costas-Ferreira, C., Pantoja, A., and Durán, R. (2022) Protective effects of antioxidants on striatal dopamine release induced by organophosphorus pesticides, Pest. Biochem. Physiol., 182, 105035, https://doi.org/10.1016/j.pestbp.2022.105035.

    Article  CAS  Google Scholar 

  5. Alimohammadi, M., Soodi, M., and Gholami Fesharaki, M. (2019) Organophosphate pesticide exposure reduced serum paraoxonase 1 (PON1) activity which correlated with oxidative stress in pesticide factory workers, Arch Hyg Sci., 8, 88-97, https://doi.org/10.29252/ArchHygSci.8.2.88.

    Article  CAS  Google Scholar 

  6. Jafari, M., Salehi, M., Asgari, A., Ahmadi, S., Abbasnezhad, M., Hajihoosani, R., and Hajigholamali, M. (2012) Effects of paraoxon on serum biochemical parameters and oxidative stress induction in various tissues of Wistar and Norway rats, Environ. Toxicol. Pharmacol., 34, 876-887, https://doi.org/10.1016/j.etap.2012.08.011.

    Article  CAS  PubMed  Google Scholar 

  7. Charron, M. J., Williams, L., Seki, Y., Du, X. Q., Chaurasia, B., Saghatelian, A., Summers, S. A., Katz, E. B., Vuguin, P. M., and Reznik, S. E. (2020) Antioxidant effects of N-acetylcysteine prevent programmed metabolic disease in mice, Diabetes, 69, 1650-1661, https://doi.org/10.2337/db19-1129.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Lasram, M. M., Bini Douib, I., Bouzid, K., Annabi, A., Naziha, E. E., Dhouib, H., El Fazaa, S., Abdelmoula, J., and Gharbi, N. (2014) Effects of N-acetyl-L-cysteine, in vivo, against pathological changes induced by malathion, Toxicol. Mech. Methods, 24, 294-306, https://doi.org/10.3109/15376516.2014.886003.

    Article  CAS  PubMed  Google Scholar 

  9. Yurumez, Y., Cemek, M., Yavuz, Y., Birdane, Y. O., and Buyukokuroglu, M. E. (2007) Beneficial effect of N-acetylcysteine against organophosphate toxicity in mice, Biol. Pharm. Bull., 30, 490-494, https://doi.org/10.1248/bpb.30.490.

    Article  CAS  PubMed  Google Scholar 

  10. Tahmasebi, K., Jafari, M., Izadi, F., Asgari, A., Bahadoran, H., Heydari, J., and Khazaie, S. (2020) Evaluation of prophylactic and therapeutic roles of N-acetylcysteine on biochemical and oxidative changes induced by acute poisoning of diazinon in various rat tissues, Curr. Chem. Biol., 14, 100-116, https://doi.org/10.2174/2212796814999200818094328.

    Article  CAS  Google Scholar 

  11. Shunmoogam, N., Naidoo, P., and Chilton, R. (2018) Paraoxonase (PON)-1: a brief overview on genetics, structure, polymorphisms and clinical relevance, Vasc. Health Risk Manag., 14, 137-143, https://doi.org/10.2147/VHRM.S165173.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Blanca, A. J., Ruiz‐Armenta, M. V., Zambrano, S., Salsoso, R., Miguel‐Carrasco, J. L., Fortuño, A., Revilla, E., Mate, A., and Vázquez, C. M. (2016) Leptin induces oxidative stress through activation of nadph oxidase in renal tubular cells: antioxidant effect of L-Carnitine, J. Cell Biochem., 117, 2281-2288, https://doi.org/10.1002/jcb.25526.

    Article  CAS  PubMed  Google Scholar 

  13. Berry, A., Bellisario, V., Panetta, P., Raggi, C., Magnifico, M. C., Arese, M., and Cirulli, F. (2018) Administration of the antioxidant N-acetyl-cysteine in pregnant mice has long-term positive effects on metabolic and behavioral endpoints of male and female offspring prenatally exposed to a high-fat diet, Front. Behav. Neurosci., 12, 48, https://doi.org/10.3389/fnbeh.2018.00048.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Obradovic, M., Sudar-Milovanovic, E., Soskic, S., Essack, M., Arya, S., Stewart, A. J., Gojobori, T., and Isenovic, E. R. (2021) Leptin and obesity: role and clinical implication, Front. Endocrinol., 12, 585887, https://doi.org/10.3389/fendo.2021.585887.

    Article  Google Scholar 

  15. Bełtowski, J., Wojcicka, G., and Jamroz, A. (2003) Leptin decreases plasma paraoxonase 1 (PON1) activity and induces oxidative stress: the possible novel mechanism for proatherogenic effect of chronic hyperleptinemia, Atherosclerosis, 170, 21-29, https://doi.org/10.1016/S0021-9150(03)00236-3.

    Article  CAS  PubMed  Google Scholar 

  16. Khazaie, S., Jafari, M., Heydari, J., Asgari, A., Tahmasebi, K., Salehi, M., and Abedini, M. S. (2019) Modulatory effects of vitamin C on biochemical and oxidative changes induced by acute exposure to diazinon in rat various tissues: prophylactic and therapeutic roles, J. Anim. Physiol. Anim. Nutr., 103, 1619-1628, https://doi.org/10.1111/jpn.13144.

    Article  CAS  Google Scholar 

  17. Fruhbeck, G., and Gómez-Ambrosi, J. (2001) Modulation of the leptin-induced white adipose tissue lipolysis by nitric oxide, Cell Signal., 13, 827-833, https://doi.org/10.1016/S0898-6568(01)00211-X.

    Article  CAS  PubMed  Google Scholar 

  18. Beltowski, J., Jamroz-Wisniewska, A., Borkowska, E., and Wojcicka, G. (2005) Differential effect of antioxidant treatment on plasma and tissue paraoxonase activity in hyperleptinemic rats, Pharmacol. Res., 51, 523-532, https://doi.org/10.1016/j.phrs.2005.01.007.

    Article  CAS  PubMed  Google Scholar 

  19. Bradford, M. M. (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding, Anal. Biochem., 72, 248-254, https://doi.org/10.1016/0003-2697(76)90527-3.

    Article  CAS  PubMed  Google Scholar 

  20. Van Kampen, E., and Zijlstra, W. G. (1966) Determination of Hemoglobin and Its Derivatives, In Adv. Clin. Chem., pp. 141-187, Elsevier, https://doi.org/10.1016/S0065-2423(08)60414-X.

  21. Friedewald, W. T., Levy, R. I., and Fredrickson, D. S. (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge, Clin. Chem., 18, 499-502, https://doi.org/10.1093/clinchem/18.6.499.

    Article  CAS  PubMed  Google Scholar 

  22. Gudarzi, S., Jafari, M., Pirzad Jahromi, G., Eshrati, R., Asadollahi, M., and Nikdokht, P. (2020) Evaluation of modulatory effects of saffron (Crocus sativus L.) aqueous extract on oxidative stress in ischemic stroke patients: a randomized clinical trial, Nutr. Neurosci., 25, 1137-1146, https://doi.org/10.1080/1028415X.2020.1840118.

    Article  PubMed  Google Scholar 

  23. Yamagishi, S.-I., Edelstein, D., Du, X.-L., Kaneda, Y., Guzmán, M., and Brownlee, M. (2001) Leptin induces mitochondrial superoxide production and monocyte chemoattractant protein-1 expression in aortic endothelial cells by increasing fatty acid oxidation via protein kinase A, J. Biol. Chem., 276, 25096-25100, https://doi.org/10.1074/jbc.M007383200.

    Article  CAS  PubMed  Google Scholar 

  24. Balasubramaniyan, V., Sailaja, J. K., and Nalini, N. (2003) Role of leptin on alcohol-induced oxidative stress in Swiss mice, Pharmacol. Res., 47, 211-216, https://doi.org/10.1016/S1043-6618(02)00317-1.

    Article  CAS  PubMed  Google Scholar 

  25. Mousavi, S. R., Jafari, M., Rezaei, S., Agha-alinejad, H., and Sobhani, V. (2020) Evaluation of the effects of different intensities of forced running wheel exercise on oxidative stress biomarkers in muscle, liver and serum of untrained rats, Lab. Animal., 49, 119-125, https://doi.org/10.1038/s41684-020-0503-7.

    Article  PubMed  Google Scholar 

  26. Eshrati, R., Jafari, M., Gudarzi, S., Nazari, A., Samizadeh, E., and Ghafourian Hesami, M. (2021) Comparison of ameliorative effects of Taraxacum syriacum and N-acetylcysteine against acetaminophen-induced oxidative stress in rat liver and kidney, J. Biochem., 169, 337-350, https://doi.org/10.1093/jb/mvaa107.

    Article  CAS  PubMed  Google Scholar 

  27. Isik, I., and Celik, I. (2008) Acute effects of methyl parathion and diazinon as inducers for oxidative stress on certain biomarkers in various tissues of rainbowtrout (Oncorhynchus mykiss), Pestic. Biochem. Physiol., 92, 38-42, https://doi.org/10.1016/j.pestbp.2008.06.001.

    Article  CAS  Google Scholar 

  28. Abdou, H., and El Mazoudy, R. (2010) Oxidative damage, hyperlipidemia and histological alterations of cardiac and skeletal muscles induced by different doses of diazinon in female rats, J. Hazard Mater., 182, 273-278, https://doi.org/10.1016/j.jhazmat.2010.06.026.

    Article  CAS  PubMed  Google Scholar 

  29. Astiz, M., de Alaniz, M. J., and Marra, C. A. (2009) Antioxidant defense system in rats simultaneously intoxicated with agrochemicals, Environ. Toxicol. Pharmacol., 28, 465-473, https://doi.org/10.1016/j.etap.2009.07.009.

    Article  CAS  PubMed  Google Scholar 

  30. Varo, I., Navarro, J., Nunes, B., and Guilhermino, L. (2007) Effects of dichlorvos aquaculture treatments on selected biomarkers of gilthead sea bream (Sparus aurata L.) fingerlings, Aquaculture, 266, 87-96, https://doi.org/10.1016/j.aquaculture.2007.02.045.

    Article  CAS  Google Scholar 

  31. Jafari, M., Salehi, M., Ahmadi, S., Asgari, A., Abasnezhad, M., and Hajigholamali, M. (2012) The role of oxidative stress in diazinon-induced tissues toxicity in Wistar and Norway rats, Toxicol. Mech. Methods, 22, 638-647, https://doi.org/10.3109/15376516.2012.716090.

    Article  CAS  PubMed  Google Scholar 

  32. Nurulain, S. M., Ojha, S., Tekes, K., Shafiullah, M., Kalasz, H., and Adem, A. (2015) Efficacy of N-acetylcysteine, glutathione, and ascorbic acid in acute toxicity of paraoxon to Wistar rats: survival study, Oxid. Med. Cell Longev., 2015, 329306, https://doi.org/10.1155/2015/329306.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Gholamloo, M., and Jafari, M. (2017) Study of effect of N-acetyl cysteine on reduction of paraoxon-induced oxidative stress in brain and heart tissues [in Persian], Health Res., 2, 77-85, https://doi.org/10.18869/acadpub.hrjbaq.2.2.77.

    Article  Google Scholar 

  34. Salehi, M., Jafari, M., Asgari, A., and Rasouli, J. (2016) The impact of N-acetyl cysteine on paraoxon-induced oxidative stress in rat liver and kidney [in Persian], J. Fasa Univ. Med. Sci., 6, 35-43.

    CAS  Google Scholar 

  35. Kim, J.-R., Ryu, H.-H., Chung, H. J., Lee, J. H., Kim, S. W., Kwun, W. H., Baek, S.-H., and Kim, J. H. (2006) Association of anti-obesity activity of N-acetylcysteine with metallothionein-II down-regulation, Exp. Mol. Med., 38, 162-172, https://doi.org/10.1038/emm.2006.20.

    Article  CAS  PubMed  Google Scholar 

  36. Aviram, M., Rosenblat, M., Billecke, S., Erogul, J., Sorenson, R., Bisgaier, C. L., Newton, R. S., and La Du, B. (1999) Human serum paraoxonase (PON 1) is inactivated by oxidized low density lipoprotein and preserved by antioxidants, Free Radic Biol. Med., 26, 892-904, https://doi.org/10.1016/S0891-5849(98)00272-X.

    Article  CAS  PubMed  Google Scholar 

  37. Jarvik, G. P., Tsai, N. T., McKinstry, L. A., Wani, R., Brophy, V. H., Richter, R. J., Schellenberg, G. D., Heagerty, P. J., Hatsukami, T. S., and Furlong, C. E. (2002) Vitamin C and E intake is associated with increased paraoxonase activity, Arterioscler. Thromb. Vasc. Biol., 22, 1329-1333, https://doi.org/10.1161/01.ATV.0000027101.40323.3A.

    Article  CAS  PubMed  Google Scholar 

  38. Sarandol, E., Serdar, Z., Dirican, M., and Safak, O. (2003) Effects of red wine consumption on serum paraoxonase/arylesterase activities and on lipoprotein oxidizability in healthy-men, J. Nutr. Biochem., 14, 507-512, https://doi.org/10.1016/S0955-2863(03)00099-8.

    Article  CAS  PubMed  Google Scholar 

  39. Kleemola, P., Freese, R., Jauhiainen, M., Pahlman, R., Alfthan, G., and Mutanen, M. (2002) Dietary determinants of serum paraoxonase activity in healthy humans, Atherosclerosis, 160, 425-432, https://doi.org/10.1016/S0021-9150(01)00594-9.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors would like to thank H. Mahdavi and J. Rasouli for their technical assistance.

Funding

This work was financially supported by the Chemical Injuries Research Center of Baqiyatallah University of Medical Sciences, Tehran, Iran (grant no. 1393-225).

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran

    Saeed Khazaie, Maryam Golamloo, Javad Heydari & Fatemeh Salem

  2. Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

    Mahvash Jafari

  3. Exercise Physiology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

    Alireza Asgari

  4. Neurosciences Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

    Maryam Salehi

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  1. Saeed Khazaie
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  2. Mahvash Jafari
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Contributions

Saeed Khazaie, Maryam Golamloo, Javad Heydari, Maryam Salehi, and Fatemeh Salem: Resources, visualization, investigation, formal analysis, software; Mahvash Jafari: Project administration, formal analysis, conceptualization, methodology, writing – reviewing and editing; Alireza Asgari: Supervision, conceptualization, reviewing, and editing.

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Correspondence to Mahvash Jafari.

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The authors declare no conflict of interest in financial or any other sphere. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Khazaie, S., Jafari, M., Golamloo, M. et al. Cumulative Effects of Paraoxon and Leptin on Oxidative Damages in Rat Tissues: Prophylactic and Therapeutic Roles of N-Acetylcysteine. Biochemistry Moscow 88, 165–178 (2023). https://doi.org/10.1134/S0006297923020013

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