The Remedial Effect of Ziziphus lotus Extract against Oxidative Stress Induced by Deltamethrin Pesticide in Rats
DOI:
https://doi.org/10.35516/jjps.v18i2.2445Keywords:
Natural products, Ziziphus lotus, Biochemical alterations, Deltamethrin, Oxidative stressAbstract
This study investigated the antioxidant properties of natural compounds derived from the medicinal plant Ziziphus lotus, traditionally used for treating liver disorders. The research focused on its potential to mitigate biochemical alterations induced by the pesticide Deltamethrin in rats. Thirty male Wistar albino rats were exposed to Deltamethrin (7 μl/kg/day), after which they received aqueous extract of Ziziphus lotus at three different doses (100, 200, and 400 mg/kg/day) via oral gavage. After 33 days of treatment, the animals were sacrificed, and blood samples were collected for serum biochemical analysis. Liver tissues were preserved for assessment of antioxidant activity. The extraction process yielded 20%, with a high polyphenol content of 12.04 ± 0.142 mg AGE/mL (Gallic Acid Equivalents per millilitre of extract). The DPPH assay confirmed strong antioxidant potential of the extract, with an IC₅₀ value of 0.62 ± 0.146 μg/mL. In vivo results showed that Deltamethrin exposure led to significant reductions in body weight and increases in serum levels of Aspartate Transaminase (AST), Alanine Transaminase (ALT), Alkaline Phosphatase (ALP), alpha-amylase, cholesterol, creatinine, and urea (p < 0.05 vs. control), indicating hepatotoxicity and nephrotoxicity. Additionally, antioxidant defence markers such as reduced glutathione (GSH) were diminished, while malondialdehyde (MDA) levels increased, reflecting enhanced lipid peroxidation. Treatment with Ziziphus lotus extract at all three doses ameliorated several liver and kidney function markers and restored body weight. The presence of bioactive secondary metabolites in the extract contributed to its significant biological activities, notably its potent antioxidant effects demonstrated both in vitro and in vivo.
References
Hassan R R., Micheal M, W., Badr A M., Hassan M E. and Abdel-Wahhab M A., Impact of sub chronic administration of deltamethrin on autoimmune activity in rat. Pestic Biochem Physiol. 2024; 203: 106008. DOI: https://doi.org/10.1016/j.pestbp.2024.106008
Lindsay S W., Thomas M B. and Kleinschmidt I. Threats to the effectiveness of insecticide-treated bednets for malaria control: thinking beyond insecticide resistance. Lancet Glob. Health 2021; 9:325-1331. DOI: https://doi.org/10.1016/S2214-109X(21)00216-3
Deng F., Sun J., Dou R., Yu X., Wei Z., Yang C., Zeng X. and Zhu L. Contamination of pyrethroids in agricultural soils from the yangtze river delta, China. Sci. Total Environ. 2020; 731: 139181. DOI: https://doi.org/10.1016/j.scitotenv.2020.139181
Ilyas W M., Chavan G. and Gadkari C. Deltamethrin poisoning mimicking organophosphate poisoning: a case report. Cureus. 2023; 15(1): e34303. DOI: https://doi.org/10.7759/cureus.34303
Lu Q., Sun Y., Ares I., Anadón A., Martínez M., Martínez-Larrañaga M R., Yuan Z, Wang X. and Martínez M A. Deltamethrin toxicity: A review of oxidative stress and metabolism. Envi Res. 2019; 170: 260-281. DOI: https://doi.org/10.1016/j.envres.2018.12.045
Tuzmen N., Candan N., Kaya E. and Demiryas N. Biochemical effects of chlorpyrifos and deltamethrin on altered antioxidative defense mechanisms and lipid peroxidation in rat liver. Cell Biochem. Funct. 2008; 26:119-124. DOI: https://doi.org/10.1002/cbf.1411
Kumar A., Sasmal D. and Sharma. Mechanism of deltamethrin induced thymic and splenic toxicity in mice and its protection by piperine and curcumin: in vivo study. Drug Chem. Toxicol. 2018; 41(1):33-41. DOI: https://doi.org/10.1080/01480545.2017.1286352
Boldi A M. Libraries from natural product-like scaffolds. Curr Opin Chem Biol. 2004; 8: 281-286. DOI: https://doi.org/10.1016/j.cbpa.2004.04.010
Newman D J., Cragg G M. and Snader K M. Natural products as sources of new drugs over the period 1981− 2002. J. Nat. Prod. 2003; 66: 1022-1037. DOI: https://doi.org/10.1021/np030096l
Djahra A B., Benkaddour M. and Benkherara S. Evaluation of antimicrobial activity of medicinal plant Cotula cinerea against pathogenic strains. Ponte J, 2020a; 76(4):316-322. DOI: https://doi.org/10.21506/j.ponte.2020.4.25
Djahra, A B., Benkaddour M., Zeghib K., Benkherara S., Shaieb I., Ghania A. and Bdida S. Biofungicide activity of Datura stramonium leaf extract against phytopathogenic fungi. Int. J. Bio. Agric. Res. 2019; 2(1):1-5.
Benkherara S., Bordjiba O., Harrat S. and Djahra A B. Antidiabetic potential and chemical constituents of Haloxylon scoparium aerial part, an endemic plant from Southeastern Algeria. Int. j. second. metab. 2021; 8:398-413. DOI: https://doi.org/10.21448/ijsm.990569
Djahra A B., Benkaddour M., Benkherara S. and Ouahiba B. Antioxidant and hepatoprotective Potential of Coriandrum sativum L. against hepatic injury by Lambda-cyhalothrin insecticide. J. Drug Deliv. Ther. 2020b; 10:182-188. DOI: https://doi.org/10.22270/jddt.v10i3-s.4186
Zeghib K. and Boutlelis D. A. Food additive (sodium benzoate)-induced damage on renal function and glomerular cells in rats; modulating effect of aqueous extract of Atriplex halimus L. Iran J Pharm Res. 2021; 20:296.
Chebil L., Acylation des flavonoïdes par les lipases de Candida antarctica et de Pseudomonas cepacia: études cinétique, structurale et conformationnelle. Ph.D. Thesis. National Polytechnic Institute of Lorraine. Franch. 2006: 230.
Velioglu Y., Mazza G., Gao L. and Oomah B. Antioxidant activity and total phenolics in selected fruits, vegetables, and grain products. J. Agric. Food Chem. 1998; 46: 4113-4117. DOI: https://doi.org/10.1021/jf9801973
Bravo L., Polyphenols: chemistry, dietary sources, metabolism, and nutritional significance. Nutr rev.1998; 56:317-333. DOI: https://doi.org/10.1111/j.1753-4887.1998.tb01670.x
Anderson K J., Teuber S S., Gobeille A., Cremin P., Waterhouse A L. and Steinberg FM. Walnut polyphenolics inhibit in vitro human plasma and LDL oxidation. J Nutr. 2001; 131: 2837-2842. DOI: https://doi.org/10.1093/jn/131.11.2837
[19] Matkowski A. and Piotrowska M. Antioxidant and free radical scavenging activities of some medicinal plants from the Lamiaceae. Fitoterapia, 2006; 77:346-353. DOI: https://doi.org/10.1016/j.fitote.2006.04.004
Li H B., Cheng K W., Wong C C., Fan K W., Chen F. and Jiang Y. Evaluation of antioxidant capacity and total phenolic content of different fractions of selected microalgae. Food Chem., 2007; 102:771-776. DOI: https://doi.org/10.1016/j.foodchem.2006.06.022
Benhammou N., Bekkara F A. and Panovska T K. Antiradical capacity of the phenolic compounds of Pistacia lentiscus L. and Pistacia atlantica desf. Adv. Food Sci. 2007; 29:155-161.
Litchfield J. and Wilcoxon F. A simplified method of evaluating dose-effect experiments. J Pharmacol Exp Ther. 1949; 96:99-113. DOI: https://doi.org/10.1016/S0022-3565(25)03549-9
Boutlelis D A. 2014. Etude phytochimique et activité antimicrobienne, antioxydante, antihépatotoxique du Marrube blanc ou Marrubium vulgare L. Ph.D. Thesis, Annaba University Algeria, 2014, p 114.
Djahra A B., Zoubiri F., Benkaddour M. and Gouasmia S. Antioxidant and Hepatoprotective Activity of Ephedra alata Extracts against Intoxication with Deltamethrin Pesticide in Male Rats. Pharmacophore. 2023; 14(1):19-24. DOI: https://doi.org/10.51847/JvqlbdZpR6
Bradford, M. M., A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976; 72: 248-254. DOI: https://doi.org/10.1006/abio.1976.9999
Weckbecker G. and Cory J G. Ribonucleotide reductase activity and growth of glutathione-depleted mouse leukemia L1210 cells in vitro. Can lett. 1988; 40:257-264. DOI: https://doi.org/10.1016/0304-3835(88)90084-5
Quintanilha A T. Membrane effects of vitamin E deficiency: bioenergetic and surface charge density studies of skeletal muscle and liver mitochondria. 1981. University of California.
Lee K W., Kim Y J., Lee H J. and Lee C Y. Cocoa has more phenolic phytochemicals and a higher antioxidant capacity than teas and red wine. J. Agric. Food Chem. 2003; 51:7292-7295. DOI: https://doi.org/10.1021/jf0344385
Salah B. Aspect Phytochimique et Activités Antibactérienne, Antioxydante ,Antihépatotoxique et Antinéphrotoxique de la plante Hammada scoparia (Pomel) Iljin de la région de Biskra (Sud-Est Algérien). Ph.D. Thesis. University of Annaba. Algeria. 2019. 143p.
Djemai Zoughlache S., Etude de l’activité biologique des extraits du fruit de Zizyphus lotus L. Ph.D. Thesis. University of Batna. Algeria. 2009: 196.
Djahra, A B., Benkaddour M., Benkherara S., Oualabi K., Ghania A. and Jdidi K. Evaluation of total phenolic contents and antioxidant potentials of ten medicinal plants from Algerian Sahara. Int. J. Bio. Agric. Res. 2018; 1(2):28-36.
Ibtissam L. and Djahra A. B. Phytochemical investigation of Helianthemum lippii L. aerial Dum. Cours part and evaluation for its antioxidant activities. Int. j. second. metab. 2022; 9:229-237. DOI: https://doi.org/10.21448/ijsm.999518
Jovanovic S V., Steenken S., Tosic M., Marjanovic B. and Simic M G. Flavonoids as antioxidants. J. Am. Chem. Soc. 1994; 116:4846-4851. DOI: https://doi.org/10.1021/ja00090a032
Siddhuraju P. and Becker K. The antioxidant and free radical scavenging activities of processed cowpea (Vigna unguiculata (L.) Walp.) seed extracts. Food chem. 2007; 101:10-19. DOI: https://doi.org/10.1016/j.foodchem.2006.01.004
Yuet Ping K., Darah I., Chen Y., Sreeramanan S. and Sasidharan S. Acute and subchronic toxicity study of Euphorbia hirta L. methanol extract in rats. BioMed research international. 2013; Vol 2013: 1-14 DOI: https://doi.org/10.1155/2013/182064
Ukwuani A., Abubakar M., Hassan S. and Agaie B. Toxicological studies of hydromethanolic leaves extract of Grewia crenata. Int J Pharm Sci Drug Res. 2012; 4:245-249. DOI: https://doi.org/10.25004/IJPSDR.2012.040405
Kehrer J P. Free radicals as mediators of tissue injury and disease. Crit. Rev. Toxicol. 1993; 23:21-48. DOI: https://doi.org/10.3109/10408449309104073
Mongi S., Mahfoud M., Amel B. and Kamel J. Protective effects of vitamin C against haematological and biochemical toxicity induced by deltamethrin in male Wistar rats. Ecotoxicol Environ Saf. 2011; 74:1765-1769. DOI: https://doi.org/10.1016/j.ecoenv.2011.04.003
Mossa A T H., Heikal T M. and Omara E A A. Liver damage associated with exposure to aspirin and diazinon in male rats and the ameliorative effect of selenium. Biomedicine & Aging Pathology. 2014; 4:137-145. DOI: https://doi.org/10.1016/j.biomag.2014.01.004
Boutlelis D A., Mounia B., Salah B., Hakim B., Rebiai A., Laib I., Chaima B., Djemaa F. and Islam R. Bio-Synthesis of Zinc Nanoparticle Using Helianthemum Lippii L. Extract and Improving in Rats Their Hepatoprotective Effects against Carbon Tetrachloride Induced Liver Damage. Ann Rom Soc Cell Biol. 2022; 26:1949-1963.
Prieto-Simón B., Campàs M., Andreescu S. and Marty J.L. Trends in flow-based biosensing systems for pesticide assessment. Sens. 2006; 6:1161-1186. DOI: https://doi.org/10.3390/s6101161
Singh B., Saxena A., Chandan B., Anand K., Suri O., Suri K. and Satti N. Hepatoprotective activity of verbenalin on experimental liver damage in rodents. Fitoterapia. 1998; 69:135-140.
Drotman R. and Lawhorn G. Serum enzymes as indicators of chemically induced liver damage. Drug Chem. Toxicol. 1978; 1:163-171. DOI: https://doi.org/10.3109/01480547809034433
Hayes, A W., and Kruger C L. (Eds.). Hayes' Principles and Methods of Toxicology (6e éd.). CRC Press. 2014: 2184. DOI: https://doi.org/10.1201/b17359
Ettinger S J. Pocket companion to the fourth edition of Textbook of veterinary internal medicine. WB Saunders Company, Philadelphia. 1995: 877.
AL-Zorri S G A. Some Physiological And Histological Effect Of Alcoholic Extract Tribulus Terrestris In Diabetic Female Rabbits. Ph.D. Thesis. Baghdad University. 2006: 180.
Abd Ali A R S. and Ismail H. The protective effect of honey against amikacin-induced nephrotoxicity in rats. Iraqi J Pharm Sci. 2012; 21: 85-93. DOI: https://doi.org/10.31351/vol21iss2pp85-93
Zeghib K., Boutlelis D A., Menai S. and Debouba M. Protective effect of Atriplex halimus extract against benzene-induced haematotoxicity in rats. Ukr Bioch J. 2021; 93:66-76. DOI: https://doi.org/10.15407/ubj93.04.066
Gatseva P D. and Argirova M D. High-nitrate levels in drinking water may be a risk factor for thyroid dysfunction in children and pregnant women living in rural Bulgarian areas. Int J Hyg Environ Health. 2008; 211:555-559. DOI: https://doi.org/10.1016/j.ijheh.2007.10.002
Jublanc C. and Bruckert E. Hypothyroidism and cardiovascular disease: role of new risk factors and coagulation parameters. In Seminars in Vascular Medicine, 2004: 145-151. DOI: https://doi.org/10.1055/s-2004-835372
Pearce E N. Hypothyroidism and dyslipidemia: modern concepts and approaches. Curr. Cardiol. Rep. 2004; 6:451-456. DOI: https://doi.org/10.1007/s11886-004-0054-3
Jahn C E., Schaefer E J., Taam L A., Hoofnagle J H., Lindgren F T., Albers J J., Jones E A. and Brewer H. B. Lipoprotein abnormalities in primary biliary cirrhosis: association with hepatic lipase inhibition as well as altered cholesterol esterification. World J Gastroenterol. 1985; 89: 1266-1278. DOI: https://doi.org/10.1016/0016-5085(85)90642-0
James G. and Pickering R. The protective effect of a novel compound RU 18492, on galactosamine-induced hepatotoxicity in the rat. Arzneimittel-forschung. 1976; 26: 2197-2199.
Venukumar M. and Latha M. Antioxidant activity of curculigo orchioides in carbon tetrachloride—induced hepatopathy in rats. Int J Clin Biochem Res. 2002; 17:80-87. DOI: https://doi.org/10.1007/BF02867976
Zeghib K. and Djahra A. Protective role of aqueous extract of Atriplex halimus L. Against benzene-induced damage on renal function and glomerular cells in rats. Asian J Pharm Clin Res. 2019; 12:387-392. DOI: https://doi.org/10.22159/ajpcr.2019.v12i3.30741
Sayyah M., Hadidi N. and Kamalinejad M. Analgesic and anti-inflammatory activity of Lactuca sativa seed extract in rats. J. Ethnopharmacol. 2004; 92:325-329. DOI: https://doi.org/10.1016/j.jep.2004.03.016
Qanwil, T., Malik, A., Mushtaq, A., Alamgeer, Muhamad Fayyaz Ur Rehman, M., & Gohar, U. F. Hypolipidemic and Vasoprotective Potential of Caralluma edulis: A Histological and Biochemical Study. Jordan Journal of Pharmaceutical Sciences. 2025; 18(1): 21–35. DOI: https://doi.org/10.35516/jjps.v18i1.2464
Shrestha, M., K.C., S., Sah, B. S., Kumar Jha, P., Khaitu, S., Pandey, B., Kishor Yadav, R., Gautam, A., & Yadav, B. Hydroethanolic Leaf Extract of Murraya Koenigii: Phytochemical Constituents and Biological Evaluation of its Toxicity and Antipyretic Activity in Wistar Albino Rats. Jordan Journal of Pharmaceutical Sciences. 2024; 17(4): 811–817. DOI: https://doi.org/10.35516/jjps.v17i4.2532
AlMallah, B., Al Laham, S., Alkhatib, R., & Al-Manadili, A. Evaluation of the Therapeutic Effect of Cardamom Extract on Nephropathy Induced by Aspirin in Rats Model. Jordan Journal of Pharmaceutical Sciences. 2025; 18(1): 146–159. DOI: https://doi.org/10.35516/jjps.v18i1.2668







