ORIGINAL RESEARCH
Protective Effect of Chlorella, Spirulina, and Astaxanthin Against Methotrexate- Induced Oxidative Biochemical Alterations in Liver and Kidney of Mice
 
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1
Laboratory of Cell Toxicology, Department of Biology, Faculty of Sciences, Badj-Mokhtar Annaba University, BP.12, 23000 Annaba, Algeria
 
2
Environmental Research Centre, Boughazi Saïd, PB23000 Annaba, Algeria
 
 
Submission date: 2024-06-15
 
 
Final revision date: 2024-08-22
 
 
Acceptance date: 2024-09-09
 
 
Online publication date: 2024-12-30
 
 
Publication date: 2025-11-04
 
 
Corresponding author
Ghozlene Issaad   

Laboratory of Cell Toxicology, Department of Biology, Faculty of Sciences, Badj-Mokhtar Annaba University, BP.12, 23000 Annaba, Algeria
 
 
Pol. J. Environ. Stud. 2025;34(6):7179-7188
 
KEYWORDS
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ABSTRACT
In this study, we examined the beneficial effects of Chlorella, Spirulina, and astaxanthin on methotrexate-induced oxidative injury in the kidney and liver. Astaxanthin, spirulina, and chlorella were administered orally to male mice for 8 days, and on the 5th day, methotrexate was intraperitoneally injected into the mice. The results revealed that methotrexate caused a significant decrease in body weight and food and water intake, along with a significant increase in serum AST, ALT, urea, and creatinine levels compared with controls. Methotrexate-induced oxidative effects were revealed by a marked decrease in catalase and glutathione S-transferase (GST) activity. Chlorella, Spirulina extracts, and astaxanthin markedly reversed the above-altered parameters, suggesting, therefore, their potential use for alleviating the harmful effects of methotrexate in mice. The observed biochemical changes in the treated animals compared with those of controls were supported by the liver and kidney histopathological changes.
CONFLICT OF INTEREST
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
REFERENCES (45)
1.
HAMED K.M., DIGHRIRI I.M., BAOMAR A.F., ALHARTHY B.T., ALENAZI F.E., ALALI G.H., ALOTAIBI Y., ALHUMAIDAN B.S., ALHADDAD Z.A., HUMADI A.A., ALZAHRANI S.A., ALOBAID R.H. Overview of methotrexate toxicity: a comprehensive literature review. Cureus, 14 (9), 2022. https://doi.org/10.7759/cureus....
 
2.
ALJOHANI N.I. Role of folinic acid in methotrexate-based prophylaxis of graft-versus-host disease following hematopoietic stem cell transplantation. Hematology, 26 (1), 620, 2021. https://doi.org/10.1080/160784....
 
3.
CAPPELLI L.C., SHAH A.A. The relationships between cancer and autoimmune rheumatic diseases. Best Practice & Research Clinical Rheumatology, 34 (1), 101472, 2020. https://doi.org/10.1016/j.berh....
 
4.
MOTAFEGHI F., MORTAZAVI P., ZABIHI J., SOROORI A., SAMADI MOJAVERI P., SHOKRZADEH M. Protective Effect of Resveratrol on Cytotoxicity, Genotoxicity, and Oxidative Stress Caused by Cyclophosphamide and Methotrexate in Bone Marrow Stem Cell Line and Blood Lymphocytes of the Rat. Applied In Vitro Toxicology, 9 (4), 129, 2023. https://doi.org/10.1089/aivt.2....
 
5.
ERTAŞ B., TURAN F.B., ÖZBEYLI D., YANARDAĞ R., SAÇAN Ö., ŞENER G. Protective effects of Petroselinum crispum (Parsley) extract against methotrexate-induced hepatotoxicity. European Journal of Biology, 80 (2), 173, 2021. https://doi.org/10.26650/EurJB....
 
6.
MARIN G.-E., NEAG M.-A., BURLACU C.-C., BUZOIANU A.D. The Protective Effects of Nutraceutical Components in Methotrexate-Induced Toxicity Models - An Overview. Microorganisms, 10 (10), 2053, 2022. https://doi.org/10.3390/microo....
 
7.
AFARANI M.S., MOHAMMADI M., SHOKRI M.M., MOHAMMADZADEH S. Investigation of protective effect of Matricaria chamomilla L. Extract on methotrexate-induced hepatotoxicity in Wistar rat. Brazilian Archives of Biology and Technology, 63, e20180626, 2020. https://doi.org/10.1590/1678-4....
 
8.
ÁVILA-ROMÁN J., GARCÍA-GIL S., RODRÍGUEZ-LUNA A., MOTILVA V., TALERO E. Anti-inflammatory and anticancer effects of microalgal carotenoids. Marine Drugs, 19 (10), 531, 2021. https://doi.org/10.3390/md1910....
 
9.
ASLANKOC R., OZMEN O., YALCIN A. Astaxanthin ameliorates damage to the cerebral cortex, hippocampus and cerebellar cortex caused by methotrexate. Biotechnic & Histochemistry, 97 (5), 382, 2022. https://doi.org/10.1080/105202....
 
10.
CHAUDHARI S.P., BAVISKAR D.T. Anti-inflammatory Activity of Chlorella vulgaris in Experimental models of Rats. International Journal of Pharmaceutical Investigation, 11 (4), 2021. https://doi.org/10.5530/ijpi.2....
 
11.
REGUEIRAS A., HUGUET Á., CONDE T., COUTO D., DOMINGUES P., DOMINGUES M.R., COSTA A.M., DA SILVA J.L., VASCONCELOS V., URBATZKA R. Potential anti-obesity, anti-steatosis, and anti-inflammatory properties of extracts from the microalgae chlorella vulgaris and chlorococcum amblystomatis under different growth conditions. Marine Drugs, 20 (1), 9, 2021. https://doi.org/10.3390/md2001....
 
12.
ALADAILEH S.H., KHAFAGA A.F., ABD ELHACK M.E., AL-GABRI N.A., ABUKHALIL M.H., ALFWUAIRES M.A., BIN-JUMAH M., ALKAHTANI S., ABDEL-DAIM M.M., LOTFI A., ABDELNOUR S., ALEYA L. Spirulina platensis ameliorates the sub chronic toxicities of lead in rabbits via anti-oxidative, anti-inflammatory, and immune stimulatory properties. Science of the Total Environment, 701, 134879, 2020. https://doi.org/10.1016/j.scit....
 
13.
PEREIRA C.P.M., SOUZA A.C.R., VASCONCELOS A.R., PRADO P.S. Antioxidant and anti‑inflammatory mechanisms of action of astaxanthin in cardiovascular diseases. International Journal of Molecular Medicine, 47 (1), 37, 2021. https://doi.org/10.3892/ijmm.2....
 
14.
CHANG M.X., XIONG F. Astaxanthin and its effects in inflammatory responses and inflammation-associated diseases: recent advances and future directions. Molecules, 25 (22), 5342, 2020. https://doi.org/10.3390/molecu....
 
15.
ELLMAN G.L., COURTNEY K.D., ANDRES JR V., FEATHERSTONE R.M. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochemical Pharmacology, 7 (2), 88, 1961. https://doi.org/10.1016/0006-2....
 
16.
SOHEILI M., KHOSRAVI-DARANI K. The potential health benefits of algae and micro algae in medicine: a review on Spirulina platensis. Current Nutrition & Food Science, 7 (4), 279, 2011. https://doi.org/10.2174/157340....
 
17.
VILLARÓ S., CIARDI M., MORILLAS-ESPAÑA A., SÁNCHEZ-ZURANO A., ACIÉN-FERNÁNDEZ G., LAFARGA T. Microalgae derived astaxanthin: Research and consumer trends and industrial use as food. Foods, 10 (10), 2303, 2021. https://doi.org/10.3390/foods1....
 
18.
HABIG W.H., PABST M.J., JAKOBY W.B. Glutathione S-transferases the first enzymatic step in mercapturic acid formation. Journal of Biological Chemistry, 249 (22), 7130, 1974. https://doi.org/10.1016/S0021-....
 
19.
AEBI H. Catalase in vitro. In Methods in Enzymology, 105, 121, 1984. https://doi.org/10.1016/S0076-....
 
20.
BANCROFT J.D., GAMBLE M. Theory and practice of histological techniques. 6th Edition, Churchill Livingstone. London: Elsevier health Sciences, pp. 112, 2008.
 
21.
GUNYELI I., SAYGIN M., OZMEN O. Methotrexate-induced toxic effects and the ameliorating effects of astaxanthin on genitourinary tissues in a female rat model. Archives of Gynecology and Obstetrics, 304, 985, 2021. https://doi.org/10.1007/s00404....
 
22.
EILAM Y., KHATTIB H., PINTEL N., AVNI D. Microalgae-Sustainable source for alternative proteins and functional ingredients promoting gut and liver health. Global Challenges, 7 (5), 2200177, 2023. https://doi.org/10.1002/gch2.2....
 
23.
NATARAJAN K., ABRAHAM P., KOTA R., ISAAC B. NF-κB-iNOS-COX2-TNF α inflammatory signaling pathway plays an important role in methotrexate induced small intestinal injury in rats. Food and Chemical Toxicology, 118, 766, 2018. https://doi.org/10.1016/j.fct.....
 
24.
SHIGA S., MACHIDA T., YANADA T., MACHIDA M., HIRAFUJI M., IIZUKA K. The role of nitric oxide in small intestine differs between a single and a consecutive administration of methotrexate to rats. Journal of Pharmacological Sciences, 143 (1), 30, 2020. https://doi.org/10.1016/j.jphs....
 
25.
TUFAN E., SIVAS G.G., GÜREL-GÖKMEN B., YILMAZ-KARAOĞLU S., DURSUN E., ÇALIŞKANAK E., MUHAN A., DILEK Ö., ŞENER G., TUNALI-AKBAY T. Whey protein concentrate ameliorates the methotrexate-induced liver and kidney damage. British Journal of Nutrition, 130 (10), 1704, 2023. https://doi.org/10.1017/S00071....
 
26.
AHMED Z.S.O., HUSSEIN S., GHANDOUR R.A., AZOUZ A.A., EL-SAKHAWY M.A. Evaluation of the effect of methotrexate on the hippocampus, cerebellum, liver, and kidneys of adult male albino rat: Histopathological, immunohistochemical and biochemical studies. Acta Histochemica, 123 (2), 151682, 2021. https://doi.org/10.1016/j.acth....
 
27.
DAVAN I., FAKURAZI S., ALIAS E., IBRAHIM N. ‘IZZAH, HWEI N.M., HASSAN H. Astaxanthin as a potent antioxidant for promoting bone health: an up-to-date review. Antioxidants, 12 (7), 1480, 2023. https://doi.org/10.3390/antiox....
 
28.
ELMELEH M.I., ATTIA T., ELGENDY H. Protective effect of Chlorella vulgaris and Spirulina platensis against Thioacetamide-Induced Hepatorenal toxicity in male rats. Journal of Current Veterinary Research, 5 (2), 79, 2023. https://doi.org/10.21608/jcvr.....
 
29.
LIANG F., AN X., WANG R., WU W., YANG L., ZHENG Y., ZHOU M. Microalgae-based drug delivery system for tumor microenvironment photo-modulating and synergistic chemo-photodynamic therapy of osteosarcoma. Engineered Regeneration, 5 (2), 199, 2024. https://doi.org/10.1016/j.engr....
 
30.
ERBAŞ E., ÜSTÜNDAĞ H., ÖZTÜRK E., PARLAK S.N., ATCALI T. Astaxanthin treatment reduces kidney damage and facilitates antioxidant recovery in lithium-intoxicated rats. Toxicon, 241, 107664, 2024. https://doi.org/10.1016/j.toxi....
 
31.
JALILI C., GHANBARI A., ROSHANKHAH S., SALAHSHOOR M.R. Toxic effects of methotrexate on rat kidney recovered by crocin as a consequence of antioxidant activity and lipid peroxidation prevention. Iranian Biomedical Journal, 24 (1), 39, 2020. https://doi.org/10.29252/ibj.2....
 
32.
ELSAWY H., ALZAHRANI A.M., ALFWUAIRES M., ABDEL-MONEIM A.M., KHALIL M. Nephroprotective effect of naringin in methotrexate induced renal toxicity in male rats. Biomedicine & Pharmacotherapy, 143, 112180, 2021. https://doi.org/10.1016/j.biop....
 
33.
SHALKAMI A.-G.S., HASSANEIN E.H.M., SAYED A.M., MOHAMED W.R., KHALAF M.M., HEMEIDA R.A.M. Hepatoprotective effects of phytochemicals berberine and umbelliferone against methotrexate-induced hepatic intoxication: experimental studies and in silico evidence. Environmental Science and Pollution Research, 28, 67593, 2021. https://doi.org/10.1007/s11356....
 
34.
PARTHASARATHY M., PRINCE S.E. Methotrexate-induced intestine and nephrotoxicity attenuated by Andrographis paniculata via ameliorating oxidative stress, inflammation and apoptosis. Advances in Traditional Medicine, 1, 2023. https://doi.org/10.1007/s13596....
 
35.
ALGENDY A.M., MANTAWY E.M., TADROS M.G., HELAL G.K. Methotrexate induced nephrotoxicity: possible underlying mechanisms and promising natural protective agents in experimental models. Archives of Pharmaceutical Sciences Ain Shams University, 7 (2), 457, 2023. https://doi.org/10.21608/aps.2....
 
36.
IBRAHIM I.A., SHALABY A.A., ABD ELAZIZ R.T., BAHR H.I. Chlorella vulgaris or Spirulina platensis mitigate lead acetate-induced testicular oxidative stress and apoptosis with regard to androgen receptor expression in rats. Environmental Science and Pollution Research, 28 (29), 39126, 2021. https://doi.org/10.1007/s11356....
 
37.
SAHINDOKUYUCU-KOCASARI F., AKYOL Y., OZMEN O., ERDEMLI-KOSE S.B., GARLI S. Apigenin alleviates methotrexate-induced liver and kidney injury in mice. Human & Experimental Toxicology, 40 (10), 1721, 2021. https://doi.org/10.1177/096032....
 
38.
DAR A.A., FEHAID A., ALKHATANI S., ALARIFI S., ALQAHTANI W.S., ALBASHER G., MONEIM A.E.A. The protective role of luteolin against the methotrexate-induced hepato-renal toxicity via its antioxidative, anti-inflammatory, and anti-apoptotic effects in rats. Human & Experimental Toxicology, 40 (7), 1194, 2021. https://doi.org/10.1177/096032....
 
39.
ABREU A.P., MARTINS R., NUNES J. Emerging Applications of Chlorella sp. and Spirulina (Arthrospira) sp. Bioengineering, 10 (8), 955, 2023. https://doi.org/10.3390/bioeng....
 
40.
SHABAN R.K. Physiological and Histological Effects Induced by Methotrexate Treatment on the Liver and Kidneys of Female Albino Rats and the Role of Pumpkin Seed Extract Against Them. European Journal of Modern Medicine and Practice, 4 (4), 348, 2024.
 
41.
RADHAKRISHNAN S., BHAVAN P.S., SEENIVASAN C., SHANTHI R., MURALISANKAR T. Replacement of fishmeal with Spirulina platensis, Chlorella vulgaris and Azolla pinnata on non-enzymatic and enzymatic antioxidant activities of Macrobrachium rosenbergii. The Journal of Basic & Applied Zoology, 67 (2), 25, 2014. https://doi.org/10.1016/j.joba....
 
42.
NAGUIB Y.M. Antioxidant activities of astaxanthin and related carotenoids. Journal of Agricultural and Food Chemistry, 48 (4), 1150, 2000. https://doi.org/10.1021/jf9911....
 
43.
CHAUHAN P., SHARMA H., KUMAR U., MAYACHARI A., SANGLI G., SINGH S. Protective effects of Glycyrrhiza glabra supplementation against methotrexate-induced hepato-renal damage in rats: An experimental approach. Journal of Ethnopharmacology, 263, 113209, 2020. https://doi.org/10.1016/j.jep.....
 
44.
WU L., MO W., FENG J., LI J., YU Q., LI S., DAI W. Astaxanthin attenuates hepatic damage and mitochondrial dysfunction in non-alcoholic fatty liver disease by up-regulating the FGF21/PGC‐1α pathway. British Journal of Pharmacology, 177 (16), 3760, 2020. https://doi.org/10.1111/bph.15....
 
45.
THANGARAJ M., SARAVANA B.P., THANASEKARAN J., JOEN-RONG S., MANUBOLU M., PATHAKOTI K. Phytochemicals of algae, Arthospira platensis (spirulina) Chlorella vulgaris (chlorella) and Azolla pinnata (azolla). GSC Biological and Pharmaceutical Sciences, 19 (2), 23, 2022. https://doi.org/10.30574/gscbp....
 
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