N-Acetylcysteine Mediated Regulation of MnSOD, UCP-2 and Cytochrome C Associated with Amelioration of Monocrotophos-Induced Hepatotoxicity in Rats

Jump To References Section

Authors

  • Department of Zoology, Maharshi Dayanand University, Rohtak – 124001, Haryana ,IN
  • Department of Zoology, Maharshi Dayanand University, Rohtak – 124001, Haryana ,IN
  • Department of Biochemistry, Maharshi Dayanand University, Rohtak – 124001, Haryana ,IN
  • Department of Zoology, Maharshi Dayanand University, Rohtak – 124001, Haryana ,IN

DOI:

https://doi.org/10.18311/ti/2022/v29i4/30325

Keywords:

Antioxidants, Hepatotoxicity, N-Acetylcysteine, Pesticide.
Pesticide toxicity and amelioration

Abstract

Pesticides are now a risk to the environment and public health. Monocrotophos (MCP) is known to cause organ toxicity and impart degenerative effects at cellular levels. N-acetylcysteine (NAC) is a natural antioxidant having various prophylactic properties. Male Wistar rats were given NAC (200 mg/kg b.wt), MCP (0.9 mg/kg b.wt) and NAC followed by MCP; intragastrically for 28 consecutive days. Regulation of MnSOD, UCP-2 and cytochrome c was analyzed by western blotting and polymerase chain reaction. Histology, electron microscopy and weight parameters were evaluated in the liver. MCP exposure significantly decreased body weight gain, relative liver weight, and structural changes. Altered MnSOD protein expression, decreased transcription of UCP-2 and MnSOD, and released cytochrome c indicated that oxidative stress is involved in MCP exposure. Treatment of NAC to MCP-exposed rats normalized the weight and structural changes, restored MnSOD and UCP-2 levels and prevented the release of cytochrome c. The present study suggests that the regulation of UCP-2, MnSOD and cytochrome c is involved in NAC efficacy against MCP toxicity. These findings illustrate that NAC can serve as a potential therapeutic agent for toxicity and oxidative stress in mammals. 

Downloads

Download data is not yet available.

Published

2023-02-07

How to Cite

Singh, J., Phogat, A., Kumar, V., & Malik, V. (2023). N-Acetylcysteine Mediated Regulation of MnSOD, UCP-2 and Cytochrome C Associated with Amelioration of Monocrotophos-Induced Hepatotoxicity in Rats. Toxicology International, 29(4), 515–525. https://doi.org/10.18311/ti/2022/v29i4/30325
Received 2022-05-24
Accepted 2022-08-08
Published 2023-02-07

 

References

Sarhan OMM, Al-Sahhaf ZY. Histological and biochemical effects of diazinon on liver and kidney of rabbits. Life Science Journal. 2011; 8(4):1183–1189.

Singh S, Kumar V, Kanwar R, Wani AB, Gill JPK, Ramamurthy PC, Singh J, Garg VK. Toxicity and detoxification of monocrotophos from ecosystem using different approaches: A review. Chemosphere. Elsevier; 2021; 130051. https://doi.org/10.1016/j.chemosphere.2021.130051. DOI: https://doi.org/10.1016/j.chemosphere.2021.130051

Chien MY, Yang CM, Chen CH. Organochlorine pesticide residue in Chinese herbal medicine. J Pestic Sci. 2022; 47(1):30–34. https://doi.org/10.1584/jpestics.d21-052. DOI: https://doi.org/10.1584/jpestics.D21-052

Phogat A, Singh J, Kumar V, Malik V. Toxicity of the acetamiprid insecticide for mammals: a review. Environ Chem Lett. 2022; 20(2):1453–1478. https://doi.10.1007/s10311-021-01353-1. DOI: https://doi.org/10.1007/s10311-021-01353-1

Konradsen F. Acute pesticide poisoning–a global public health problem. Dan Med Bull. Citeseer; 2007; 54(1):58–59.

Lushchak VI, Matviishyn TM, Husak VV, Storey JM, Storey KB. Pesticide toxicity: a mechanistic approach. Excli J. 2018; 17:1101–1136. https://doi.org/10.17179/excli2018-1710.

Arora K. Toxic Effects of Monocrotophos (an organophosphate) on Histoarchitecture of Liver–Histopathological Studies. Int J Biotechnol Biochem. 2009; 5(4):445–450.

Sankhwar ML, Yadav RS, Shukla RK, Singh D, Ansari RW, Pant AB, Parmar D, Khanna VK. Monocrotophos induced oxidative stress and alterations in brain dopamine and serotonin receptors in young rats. Toxicol Ind Health. 2016; 32(3):422–436.

https://doi.org/10.1177/0748233713500834. DOI: https://doi.org/10.1177/0748233713500834

Devi S, Singh J, Kumar V, Malik V. Monocrotophos induced Biochemical and Histopathological alterations in the Kidney tissues of Mice. Chem Biol Lett. 2019; 6(2):39–45.

Malik V, Singh J, Kumar A, Kumar V. Protective effect of coenzyme Q10 nanoparticles against monocrotophos induced oxidative stress in kidney tissues of rats. Biologia. 2021; 76:1849-1857. https://doi.org/10.1007/s11756-021-00732-x. DOI: https://doi.org/10.1007/s11756-021-00732-x

Loevinsohn M. Insecticide use and increased mortality in rural Central Luzon, Philippines. The Lancet. 1987; 329(8546):1359–1362. https://doi.org/10.1016/s0140-6736(87)90659-3. DOI: https://doi.org/10.1016/S0140-6736(87)90659-3

Hirshhorn N. Study of the occupational health of Indonesian farmers who spray pesticides. The Indonesian National IPM Program, FAO, Jakarta. 1993; 23:12–16.

Singh J, Phogat A, Prakash C, Chhikara SK, Singh S, Malik V, Kumar V. N-Acetylcysteine Reverses Monocrotophos Exposure-Induced Hepatic Oxidative Damage via Mitigating Apoptosis, Inflammation and Structural Changes in Rats. Antioxidants (Basel). 2021; 11(1):90. https://doi.org/10.3390/antiox11010090. DOI: https://doi.org/10.3390/antiox11010090

Matsunaga K, Fukunaga S, Abe J, Takeuchi H, Kitamoto S, Tomigahara Y. Comparative hepatotoxicity of a herbicide, epyrifenacil, in humans and rodents by comparing the dynamics and kinetics of its causal metabolite. J Pestic Sci. 2021; 46(4):333–341. https://doi.org/10.1584/jpestics.d21-026. DOI: https://doi.org/10.1584/jpestics.D21-026

Yaduvanshi SK, Ojha A, Pant SC, Lomash V, Srivastava N. Monocrotophos induced lipid peroxidation and oxidative DNA damage in rat tissues. Pestic Biochem Phys. 2010; 97(3):214–222. https://doi.org/10.1016/j.pestbp.2010.02.004. DOI: https://doi.org/10.1016/j.pestbp.2010.02.004

Sunmonu TO, Oloyede OB. Monocrotophos–induced enzymatic changes as toxicity bio-markers in Wistar Rat liver. Agriculture and Biology Journal of North America. 2012; 2151:7525. DOI: https://doi.org/10.5251/abjna.2012.3.7.302.305

Karumuri SB, Singh H, Naqvi S, Mishra A, Flora SJS. Impact of chronic low dose exposure of monocrotophos in rat brain: Oxidative/ nitrosative stress, neuronal changes and cholinesterase activity. Toxicol Rep. 2019; 6:1295–1303. https://doi.org/10.1016/j.toxrep.2019.11.005. DOI: https://doi.org/10.1016/j.toxrep.2019.11.005

Nagaraju R, Joshi AKR, Vamadeva SG, Rajini PS. Deregulation of hepatic lipid metabolism associated with insulin resistance in rats subjected to chronic monocrotophos exposure. J Biochem Mol Toxicol 2020; 34(8):e22506. https://doi/abs/10.1002/jbt.22506. DOI: https://doi.org/10.1002/jbt.22506

Begum K, Rajini PS. Augmentation of hepatic and renal oxidative stress and disrupted glucose homeostasis by monocrotophos in streptozotocin-induced diabetic rats. Chem-Biol Interact. 2011; 193(3):240–245. https://doi.org/10.1016/j.cbi.2011.07.003. DOI: https://doi.org/10.1016/j.cbi.2011.07.003

Elbini Dhouib I, Jallouli M, Annabi A, Gharbi N, Elfazaa S, Lasram MM. A minireview on N-acetylcysteine: An old drug with new approaches. Life Sci. 2016; 151:359–363. https://doi.org/10.1016/j.lfs.2016.03.003. DOI: https://doi.org/10.1016/j.lfs.2016.03.003

Bavarsad Shahripour R, Harrigan MR, Alexandrov AV. N-acetylcysteine (NAC) in neurological disorders: mechanisms of action and therapeutic opportunities. Brain Behav. 2014; 4(2):108–122. https://doi.org/10.1002/brb3.208. DOI: https://doi.org/10.1002/brb3.208

Abdel-Daim MM, Dessouki AA, Abdel-Rahman HG, Eltaysh R, Alkahtani S. Hepatorenal protective effects of taurine and N-acetylcysteine against fipronil-induced injuries: The antioxidant status and apoptotic markers expression in rats. Sci Total Environ. 2019; 650:2063–2073. https://doi.org/10.1016/j.scitotenv.2018.09.313. DOI: https://doi.org/10.1016/j.scitotenv.2018.09.313

Ghafarizadeh A, Malmir M, Naderi Noreini S, Faraji T. Antioxidant effects of N-acetylcysteine on the male reproductive system: A systematic review. Andrologia. 2021; 53(1):e13898. https://doi.org/10.1111/and.13898. DOI: https://doi.org/10.1111/and.13898

Singh J, Phogat A, Kumar V, Malik V. N-acetylcysteine ameliorates monocrotophos exposure-induced mitochondrial dysfunctions in rat liver. Toxicol Mech Methods. 2022; 1–29. https://doi.org/10.1080/15376516.2022.2064258. DOI: https://doi.org/10.1080/15376516.2022.2064258

Ahmad I, Shukla S, Kumar A, Singh BK, Kumar V, Chauhan AK, Singh D, Pandey HP, Singh C. Biochemical and molecular mechanisms of N-acetyl cysteine and silymarin-mediated protection against maneb- and paraquat-induced hepatotoxicity in rats. Chem Biol Interact. 2013; 201(1–3):9–18. https://doi.org/10.1016/j.cbi.2012.10.027. DOI: https://doi.org/10.1016/j.cbi.2012.10.027

Galal AAA, Ramadan RA, Metwally MMM, El-Sheikh SMA. Protective effect of N-acetylcysteine on fenitrothion-induced toxicity: The antioxidant status and metabolizing enzymes expression in rats. Ecotoxicol Environ Saf. 2019; 171:502–510. https://doi.org/10.1016/j.ecoenv.2019.01.004. DOI: https://doi.org/10.1016/j.ecoenv.2019.01.004

Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193(1):265–275. DOI: https://doi.org/10.1016/S0021-9258(19)52451-6

Waite DT, Sommerstad H, Grover R, Kerr L, Westcott ND. Pesticides in ground water, surface water and spring runoff in a small Saskatchewan watershed. Environmental Toxicology and Chemistry: An International Journal. 1992; 11(6):741–748. DOI: https://doi.org/10.1002/etc.5620110603

Huang Y, Shi T, Luo X, Xiong H, Min F, Chen Y, Nie S, Xie M. Determination of multi-pesticide residues in green tea with a modified QuEChERS protocol coupled to HPLC-MS/MS. Food Chem. 2019; 275:255–264. https://doi.org/10.1016/j.foodchem.2018.09.094. DOI: https://doi.org/10.1016/j.foodchem.2018.09.094

Mansour SA, Mossa ATH. Oxidative damage, biochemical and histopathological alterations in rats exposed to chlorpyrifos and the antioxidant role of zinc. Pestic Biochem Physiol. 2010; 96(1):14–23. https://doi.org/10.1016/j.pestbp.2009.08.008. DOI: https://doi.org/10.1016/j.pestbp.2009.08.008

Sunmonu TO, Oloyede OB. Performance and haematological indices in rats exposed to monocrotophos contamination. Hum Exp Toxicol. 2010; 29(10):845–850. https://doi.org/10.1177/0960327110363441. DOI: https://doi.org/10.1177/0960327110363441

Wani WY, Gudup S, Sunkaria A, Bal A, Singh PP, Kandimalla RJL, Sharma DR, Gill KD. Protective efficacy of mitochondrial targeted antioxidant MitoQ against dichlorvos induced oxidative stress and cell death in rat brain. Neuropharmacology. 2011; 61(8):1193–1201. https://doi.org/10.1016/j.neuropharm.2011.07.008. DOI: https://doi.org/10.1016/j.neuropharm.2011.07.008

Kaur P, Radotra B, Minz R, Gill K. Impaired mitochondrial energy metabolism and neuronal apoptotic cell death after chronic dichlorvos (OP) exposure in rat brain. NeuroToxicology. 2007; 28(6):1208–1219. https://doi.org/10.1016/j.neuro.2007.08.001. DOI: https://doi.org/10.1016/j.neuro.2007.08.001

Li N, Ragheb K, Lawler G, Sturgis J, Rajwa B, Melendez JA, Robinson JP. DPI induces mitochondrial superoxide-mediated apoptosis. Free Radic Biol Med. 2003; 34(4):465–477. https://doi.org/10.1016/s0891-5849(02)01325-4. DOI: https://doi.org/10.1016/S0891-5849(02)01325-4

Zhu Y, Kalen AL, Li L, Lehmler HJ, Robertson LW, Goswami PC, Spitz DR, Aykin-Burns N. Polychlorinated-biphenyl-induced oxidative stress and cytotoxicity can be mitigated by antioxidants after exposure. Free Radic Biol Med. 2009; 47(12):1762–1771. https://doi.org/10.1016/j.freeradbiomed.2009.09.024. DOI: https://doi.org/10.1016/j.freeradbiomed.2009.09.024

Allam A, Abdeen A, Devkota HP, Ibrahim SS, Youssef G, Soliman A, Abdel-Daim MM, Alzahrani KJ, Shoghy K, Ibrahim SF, Aboubakr M. N-Acetylcysteine Alleviated the Deltamethrin-Induced Oxidative Cascade and Apoptosis in Liver and Kidney Tissues. Int J Environ Res Public Health. 2022; 19(2):638. https://doi.org/10.3390/ijerph19020638. DOI: https://doi.org/10.3390/ijerph19020638

Prakash C, Soni M, Kumar V. Biochemical and Molecular Alterations Following Arsenic-Induced Oxidative Stress and Mitochondrial Dysfunction in Rat Brain. Biol Trace Elem Res. 2015; 167(1):121–129. https://doi.org/10.1007/s12011-015-0284-9. DOI: https://doi.org/10.1007/s12011-015-0284-9

Soni M, Prakash C, Sehwag S, Kumar V. Protective effect of hydroxytyrosol in arsenic-induced mitochondrial dysfunction in rat brain. J Biochem Mol Toxicol. 2017; 31(7). https://doi.org/10.1002/jbt.21906. DOI: https://doi.org/10.1002/jbt.21906

Alhusaini A, Fadda LM, Ali HM, Hasan IH, Ali RA, Zakaria EA. Mitigation of acetamiprid-induced renotoxicity by natural antioxidants via the regulation of ICAM, NF-kB and TLR 4 pathways. Pharmacol Rep. 2019; 71(6):1088–1094. https://doi.org/10.1016/j.pharep.2019.06.008. DOI: https://doi.org/10.1016/j.pharep.2019.06.008

Ahmad A, Kumari P, Ahmad M. Apigenin attenuates edifenphos-induced toxicity by modulating ROS-mediated oxidative stress, mitochondrial dysfunction and caspase signal pathway in rat liver and kidney. Pestic Biochem Physiol. 2019; 159:163–172. https://doi.org/10.1016/j.pestbp.2019.06.010. DOI: https://doi.org/10.1016/j.pestbp.2019.06.010

Firouzian F, Pourshoja P, Nili-Ahmadabadi A, Ranjbar A. Hepatoprotective effect of N-acetylcystein loaded niosomes on liver function in paraquat-induced acute poisoning. Pestic Biochem Physiol. 2019; 160:146–153. https://doi.org/10.1016/j.pestbp.2019.08.001. DOI: https://doi.org/10.1016/j.pestbp.2019.08.001