Jundishapur Scientific Medical Journal

Jundishapur Scientific Medical Journal

Investigating the Antioxidant Effects of Hesperidin on Liver Tissue in Mice with Acute Malathion Toxicity

Document Type : Original Article

Authors
1 Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran.
2 Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran..
3 Assistant Professor of Anatomical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
Abstract
Background and Objectives Malathion is an organophosphate compound that can cause severe damage to organs such as the liver. It exerts its toxic effects through inhibition of cholinesterase and induction of oxidative stress. Hesperidin, a flavonoid with antioxidant and anti-inflammatory properties, may have a protective role against this damage. The aim of this study was to investigate the protective effect of hesperidin against acute malathion-induced liver injury in female Syrian mice.
Subjects and Methods In this experimental study, 32 female Syrian mice were randomly divided into four groups: negative control, malathion, hesperidin, and treatment (malathion + hesperidin). Malathion (3 mg/kg) and hesperidin (20 mg/kg) were administered intraperitoneally for 35 consecutive days. At the end of the treatment period, following anesthesia, cardiac blood sampling and liver tissue collection were performed. Data were analyzed using SPSS version 24, with statistical significance set at (p<0.05).
Results In the malathion group, histopathological alterations in liver tissue were observed, and serum levels of ALT, AST, ALP, and both total and direct bilirubin were significantly increased (P<0.05). In the treatment group, these markers were significantly reduced, and histological improvement of liver tissue was evident (P<0.05). Total antioxidant capacity (TAC) decreased in the malathion group while it increased in the hesperidin and treatment groups (P<0.05). Additionally, malondialdehyde (MDA) levels were significantly elevated in the malathion group but significantly reduced in the malathion+hesperidin group (P<0.05).
Conclusion Malathion induced histopathological changes and enzymatic disturbances in the liver, whereas hesperidin effectively mitigated these effects. Therefore, hesperidin may serve as a protective agent against malathion-induced hepatotoxicity.
Keywords
Subjects

1.Gin S, Prasad SB, Giri A, Sharma GD. Genotoxic effects of malathion: an organophosphorous insecticide using three mammalian biossays in vitro. Mutat Res. 2002;514:223-31.[ 10.1016/s1383-5718(01)00341-2] [PMID]
2.Elmorsy E, Al-Ghafari A, Al Doghaither H, Salama M, Carter WG. An Investigation of the Neurotoxic Effects of Malathion, Chlorpyrifos, and Paraquat to Different Brain Regions. Brain Sci. 2022;12(8). [10.3390/ brainsci12080975][PMID]
3.Severcan Ç, Ekremoglu M, Sen B, Pasaoglu O, Akyurek N, Severcan S, Pasaoglu H. Acute effects of different doses of malathion on the rat liver. Clinical and Experimental Hepatology. 2019 Sep 5;5(3):237-43. [10.5114/ceh.2019.87637][PMID]
4.Hernández-Toledano DS, Estrada-Muñiz E, Vega L. Genotoxicity of the organophosphate pesticide malathion and its metabolite dimethylthiophosphate in human cells in vitro. Mutation research Genetic toxicology and environmental mutagenesis. 2020;856-857:503233. [10.1016/j.mrgentox.2020.503233][PMID]
5.Buratti FM, D’Aniello A, Volpe MT, Meneguz A, Testai E. Malathion bioactivation in the human liver: the contribution of different cytochrome P450 isoforms. Drug metabolism and disposition. 2005 Mar 1;33(3):295-302. [10.1124/dmd.104.001693][PMID]
6.Karami-Mohajeri S, Hadian MR, Fouladdel S, Azizi E, Ghahramani MH, Hosseini R, et al. Mechanisms of muscular electrophysiological and mitochondrial dysfunction following exposure to malathion, an organophosphorus pesticide. Human & experimental toxicology. 2014;33(3):251-63. [10.1177/0960327113 493300][PMID]
7.Pyrzynska K. Hesperidin: A Review on Extraction Methods, Stability and Biological Activities. Nutrients. 2022;14(12). [10.3390/nu14122387][PMID]
8.Buzdağlı Y, Eyipınar CD, Kacı FN, Tekin A. Effects of hesperidin on anti-inflammatory and antioxidant response in healthy people: a meta-analysis and meta-regression. International journal of environmental health research. 2023;33(12):1390-405. [10.1080/09603123. 2022. 2093841][PMID]
9.Küçükler S, Çomaklı S, Özdemir S, Çağlayan C, Kandemir FM. Hesperidin protects against the chlorpyrifos‐induced chronic hepato‐renal toxicity in rats associated with oxidative stress, inflammation, apoptosis, autophagy, and up‐regulation of PARP‐1/VEGF. Environmental toxicology. 2021 Aug;36(8):1600-17. [10.1002/tox.23156][PMID]
10.Talebi SF, Kooshki A, Zarein M, Seify M, Dolatshahi B, Shoorei H, et al. Protective effect of hesperidin on malathion-induced ovarian toxicity in mice: The role of miRNAs, inflammation, and apoptosis. Toxicology reports. 2024;12:469-76. [10.1016/j.toxrep.2024. 04.003] [PMID]
11.Panahi P, Vosough-Ghanbari S, Pournourmohammadi S, Ostad SN, Nikfar S, Minaie B, et al. Stimulatory effects of malathion on the key enzymes activities of insulin secretion in langerhans islets, glutamate dehydrogenase and glucokinase. Toxicology mechanisms and methods. 2006;16(4):161-7. [10.1080/ 15376520500191623] [PMID]
12.Pari L, Karthikeyan A, Karthika P, Rathinam A. Protective effects of hesperidin on oxidative stress, dyslipidaemia and histological changes in iron-induced hepatic and renal toxicity in rats. Toxicology reports. 2015;2:46-55. [10.1016/j.toxrep.2014.11.003][PMID]
13.Dai C, Xiao X, Li D, Tun S, Wang Y, Velkov T, et al. Chloroquine ameliorates carbon tetrachloride-induced acute liver injury in mice via the concomitant inhibition of inflammation and induction of apoptosis. Cell death & disease. 2018;9(12):1164. [10.1038/s41419-018-1136-2] [PMID]
14.Gur C, Kandemir FM. Molecular and biochemical investigation of the protective effects of rutin against liver and kidney toxicity caused by malathion administration in a rat model. Environmental toxicology. 2023;38(3):555-65. [10.1002/tox.23700][PMID]
15.Singh D, Cho WC, Upadhyay G. Drug-Induced Liver Toxicity and Prevention by Herbal Antioxidants: An Overview. Frontiers in physiology. 2015;6:363. [][PMID]
16.Rezg R, Mornagui B, Kamoun A, El-Fazaa S, Gharbi NJCRB. Effect of subchronic exposure to malathion on metabolic parameters in the rat. 2007;330(2):143-7. [10.3389/fphys.2015.00363][PMID]
17.Lasram MM, Lamine AJ, Dhouib IB, Bouzid K, Annabi A, Belhadjhmida N, et al. Antioxidant and anti-inflammatory effects of N-acetylcysteine against malathion-induced liver damages and immunotoxicity in rats. Life sciences. 2014;107(1-2):50-8. [10.1016/j.lfs. 2014.04.033][PMID]
18.Flehi-Slim I, Chargui I, Boughattas S, El Mabrouk A, Belaïd-Nouira Y, Neffati F, et al. Malathion-induced hepatotoxicity in male Wistar rats: biochemical and histopathological studies. Environmental science and pollution research international. 2015;22(22):17828-38. [10.1007/s11356-015-5014-5][PMID]
19.Karabekir SC, Sozen ME, Ayan IC, Savas HB, Cuce G, Kalkan S. The ameliorative effects of hesperidin in rats developed hepatotoxicity with deltamethrin. Iranian journal of basic medical sciences. 2025;28(7):929-36. [10.22038/ijbms.2025.82598.17854][PMID]
20.Cheraghpour M, Imani H, Ommi S, Alavian SM, Karimi-Shahrbabak E, Hedayati M, et al. Hesperidin improves hepatic steatosis, hepatic enzymes, and metabolic and inflammatory parameters in patients with nonalcoholic fatty liver disease: A randomized, placebo-controlled, double-blind clinical trial. Phytotherapy research : PTR. 2019;33(8):2118-25. [10.1002/ptr.6406][PMID]
21.Caglayan C, Kandemir FM, Darendelioğlu E, Küçükler S, Ayna A. Hesperidin protects liver and kidney against sodium fluoride-induced toxicity through anti-apoptotic and anti-autophagic mechanisms. Life Sciences. 2021;281:119730. [10.1016/j.lfs.2021.119730][PMID]
22.Selmi S, Rtibi K, Grami D, Sebai H, Marzouki L. Malathion, an organophosphate insecticide, provokes metabolic, histopathologic and molecular disorders in liver and kidney in prepubertal male mice. Toxicology reports. 2018;5:189-95. [10.1016/j.toxrep. 2017.12 .021] [PMID]
23.Kalender S, Uzun FG, Durak D, Demir F, Kalender Y. Malathion-induced hepatotoxicity in rats: the effects of vitamins C and E. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 2010;48(2):633-8. [10.1016/j.fct.2009.11.044][PMID]
24.Saati AA. Hesperidin Alleviates Malathion-Induced nephrotoxicity in Rats: Impact on Oxidative Damage, Inflammation, Pyroptosis and Apoptosis. Bulletin of Egyptian Society for Physiological Sciences. 2025;45(1):95-108.
25.Hassan RA, Hozayen WG, Abo Sree HT, Al-Muzafar HM, Amin KA, Ahmed OM. Naringin and Hesperidin Counteract Diclofenac-Induced Hepatotoxicity in Male Wistar Rats via Their Antioxidant, Anti-Inflammatory, and Antiapoptotic Activities. Oxidative medicine and cellular longevity. 2021;2021:9990091. [10.1155/ 2021/ 9990091][PMID]
26.Al-Rikabi R, Al-Shmgani H, Dewir YH, El-Hendawy S. In vivo and in vitro Evaluation of the Protective Effects of Hesperidin in Lipopolysaccharide-Induced Inflammation and Cytotoxicity of Cell. Molecules (Basel, Switzerland). 2020;25(3). [10.3390/molecules25030478][PMID]
27.Çetin A, Çiftçi O, Otlu A. Protective effect of hesperidin on oxidative and histological liver damage following carbon tetrachloride administration in Wistar rats. Archives of medical science : AMS. 2016;12(3):486-93. [10.5114/aoms.2015.49484][PMID]
28.Mahmoud AM, Mohammed HM, Khadrawy SM, Galaly SR. Hesperidin protects against chemically induced hepatocarcinogenesis via modulation of Nrf2/ARE/HO-1, PPARγ and TGF-β1/Smad3 signaling, and amelioration of oxidative stress and inflammation. Chemico-biological interactions. 2017;277:146-58. [10.1016/j.cbi.2017. 09. 015][PMID]
29.Freyre EO, Valencia AT, Guzmán DD, Maldonado IC, Ledezma LE, Carrillo MF, Escorza MA. Oxidative stress as a molecular mechanism of exposure to organophosphorus pesticides: a review. Current Protein and Peptide Science. 2021 Dec 1;22(12):890-7.
 
 
Authors retain the copyright and full publishing rights.
Published by Ahvaz Jundishapur University of Medical Science. This article is an open access article licensed under the Creative Commons Attribution-NonCommercial 4.0 (https://creativecommons.org/licenses/by-nc/4.0/).
 
30.Althobaiti SA. MitoQ alleviates malathion‑induced hepatorenal toxicity via oxidative stress and inflammation modulation. Molecular medicine reports. 2025;32(5). [10.3892/mmr.2025.13661][PMID]
31.Abdel-Salam OM, Youness ER, Mohammed NA, Yassen NN, Khadrawy YA, El-Toukhy SE, Sleem AA. Nitric oxide synthase inhibitors protect against brain and liver damage caused by acute malathion intoxication. Asian Pacific journal of tropical medicine. 2017 Aug 1;10(8):773-86.
32.Eid RA, Abadi AM, Alghamdi MA, El-Kott AF, Mohamed G, Al-Shraim M, et al. Echinops Asteraceae extract guards against malathion-induced liver damage via minimizing oxidative stress, inflammation, and apoptosis. Toxicon : official journal of the International Society on Toxinology. 2024;244:107750. [10.1016/j.toxicon. 2024. 107750][PMID]
33.Ghamry HI, Aboushouk AA, Soliman MM, Albogami SM, Tohamy HG, Okle OSE, et al. Ginseng(®) Alleviates Malathion-Induced Hepatorenal Injury through
Volume 25, Issue 1 - Serial Number 160
Issue in Progress
2026
Pages 1-11

  • Receive Date 21 October 2025
  • Revise Date 13 December 2025
  • Accept Date 17 February 2026