Abstract:
Background: Astaxanthin, a marine-derived carotenoid, possesses potent antioxidant and anti-inflammatory properties with potential therapeutic effects in liver diseases. Specific Background: Diazinon, a widely used organophosphorus pesticide, induces hepatotoxicity through oxidative stress and inflammation. Knowledge Gap: Although astaxanthin’s antioxidant potential is recognized, its protective role against diazinon-induced liver injury remains underexplored. Aim: This study investigated the hepatoprotective effects of astaxanthin against diazinon-induced liver toxicity in male rats. Results: Thirty rats were divided into five groups and treated with diazinon alone or in combination with astaxanthin (50 mg/kg and 100 mg/kg), vitamin C, or distilled water for 30 days. Diazinon exposure significantly elevated serum ALT, AST, and IL-1β levels, reduced hepatic GPx activity, and caused histopathological liver damage. Astaxanthin pre-treatment, particularly at 100 mg/kg, significantly attenuated these effects by normalizing enzyme levels, reducing inflammatory markers, enhancing antioxidant activity, and preserving liver histology. Novelty: This study is among the first to demonstrate astaxanthin’s dose-dependent hepatoprotective effect against organophosphate-induced toxicity. Implications: Astaxanthin shows promise as a therapeutic agent for mitigating liver damage caused by environmental toxins, warranting further clinical and mechanistic investigations.
Highlights:
Astaxanthin lowers AST, ALT, IL-1β in treated rats.
Liver histology improved with astaxanthin pre-treatment.
Shows promise as hepatoprotective agent against diazinon toxicity.
Keywords: Diazinon, Astaxanthin, vitamin C, Antioxidants, hepatotoxicity
References
C. García‐Ruiz and J. C. Fernández‐Checa, “Mitochondrial oxidative stress and antioxidants balance in fatty liver disease,” Hepatol. Commun., vol. 2, no. 12, pp. 1425–1439, 2018.
A. Ranjan and T. Jindal, Toxicology of organophosphate poisoning. Springer, 2022.
M. Zeinali, N. T. Meybodi, S. A. Rezaee, H. Rafatpanah, and H. Hosseinzadeh, “Protective effects of chrysin on sub-acute diazinon-induced biochemical, hematological, histopathological alterations, and genotoxicity indices in male BALB/c mice,” Drug Chem. Toxicol., vol. 41, no. 3, pp. 270–280, 2018.
W. Lu et al., “Antioxidant activity and healthy benefits of natural pigments in fruits: A review,” Int. J. Mol. Sci., vol. 22, no. 9, p. 4945, 2021.
P. Irato and G. Santovito, “Enzymatic and non-enzymatic molecules with antioxidant function,” 2021, MDPI.
Y. Nishida et al., “Astaxanthin: past, present, and future,” Mar. Drugs, vol. 21, no. 10, p. 514, 2023.
J. Li, C. Guo, and J. Wu, “Astaxanthin in liver health and disease: a potential therapeutic agent,” Drug Des. Devel. Ther., pp. 2275–2285, 2020.
V. Lala, M. Zubair, and D. Minter, “Liver function tests,” StatPearls, 2023.
S. B. Coco-Bassey et al., “Glutathione, glutathione peroxidase and some hematological parameters of HIV-seropositive subjects attending clinic in University of Calabar teaching hospital, Calabar, Nigeria,” BMC Infect. Dis., vol. 19, pp. 1–10, 2019.
N. Nazar, M. H. Mehmood, R. Siddique, and M. N. Faisal, “Assessment of antiarthritic potential of Asparagus dumosus using formaldehyde and CFA-induced arthritic models in rats via modulation of oxidative stress biomarkers and mRNA expression of IL-1b, IL-6, RANKL, OPG, TNF-α and COX-2,” Inflammopharmacology, vol. 32, no. 1, pp. 825–847, 2024.
E. A. Sampedro-Carrillo, “Sample preparation and fixation for histology and pathology,” Immunohistochem. Immunocytochem. Methods Protoc., pp. 33–45, 2021.
G.-H. Danaei, A. Amali, M. Karami, M.-B. Khorrami, B. Riahi-Zanjani, and M. Sadeghi, “The significance of thymoquinone administration on liver toxicity of diazinon and cholinesterase activity; a recommendation for prophylaxis among individuals at risk,” BMC Complement. Med. Ther., vol. 22, no. 1, p. 321, 2022.
L. Ezzi et al., “Toxicopathic changes and genotoxic effects in liver of rat following exposure to diazinon,” Environ. Sci. Pollut. Res., vol. 23, pp. 11163–11170, 2016.
H. Beydilli et al., “Evaluation of the protective effect of silibinin against diazinon induced hepatotoxicity and free-radical damage in rat liver,” Iran. Red Crescent Med. J., vol. 17, no. 4, 2015.
A.-T. H. Mossa, T. M. Heikal, and E. A. A. Omara, “Physiological and histopathological changes in the liver of male rats exposed to paracetamol and diazinon,” Asian Pac. J. Trop. Biomed., vol. 2, no. 3, pp. S1683–S1690, 2012.
A. Laderian, M. Ghasemi, P. Mortazavi, Z. Mousavi, and M. Ale‐Ebrahim, “Hepatoprotective effect of astaxanthin against cholestasis liver fibrosis induced by bile duct ligation in adult Wistar rats,” J. Biochem. Mol. Toxicol., vol. 38, no. 8, p. e23788, 2024.
S. M. Abou-Zeid et al., “Astaxanthin mitigates thiacloprid-induced liver injury and immunotoxicity in male rats,” Mar. Drugs, vol. 19, no. 9, p. 525, 2021.
F. M. Mohammadrezaei, Z. G. Ganji, A. Nili-Ahmadabadi, and A. H. Moghaddam, “Therapeutic Potential of Astaxanthin Against Cadmium-Induced Hepatic Failure: An Experimental Study: Astaxanthin and Cadmium Hepatotoxicity,” Iran. J. Pharm. Sci., vol. 18, no. 1, pp. 1–7, 2022.
R. Azadian, A. Mohammadalipour, M. R. Memarzadeh, M. Hashemnia, and M. H. Aarabi, “Examining hepatoprotective effects of astaxanthin against methotrexate-induced hepatotoxicity in rats through modulation of Nrf2/HO-1 pathway genes,” Naunyn. Schmiedebergs. Arch. Pharmacol., vol. 397, no. 1, pp. 371–380, 2024.
L. Wang and L. Zhuang, “Astaxanthin ameliorates the lipopolysaccharides-induced subfertility in mouse via Nrf2/HO-1 antioxidant pathway,” Dose-Response, vol. 17, no. 3, p. 1559325819878537, 2019.
S. R. Ivanović, N. Borozan, D. Ć. Miladinović, I. Živković, and S. Borozan, “The relationship between the cholinergic mechanism of toxicity and oxidative stress in rats during subacute diazinon poisoning,” Toxicol. Appl. Pharmacol., vol. 473, p. 116598, 2023, doi: 10.1016/j.taap.2023.116598.
K. Li, W. Wang, and W. Xiao, “Astaxanthin : A promising therapeutic agent for organ fibrosis,” vol. 188, no. October 2022, 2023, doi: 10.1016/j.phrs.2023.106657.
P. Monmeesil, W. Fungfuang, P. Tulayakul, and U. Pongchairerk, “The effects of astaxanthin on liver histopathology and expression of superoxide dismutase in rat aflatoxicosis,” J. Vet. Med. Sci., vol. 81, no. 8, pp. 1162–1172, 2019.