The effect of garlic (Allium sativum) on hepatic and renal functions in male rabbits exposed to zinc oxide
Effect of garlic on zinc-induced hepato-renal toxicity
DOI:
https://doi.org/10.62310/liab.v6i1.244Keywords:
Allium sativum, Zinc oxide, Oxidative stress, Pathophysiology, Toxicity, AntioxidantAbstract
Heavy metals, including zinc, are known for their high toxicity. Although zinc is an essential trace element, excessive concentrations can lead to systemic toxicity, with adverse effects on various organs, particularly the liver and kidneys – two major target organs. This study investigated the hepatotoxicity and nephrotoxicity associated with zinc oxide (ZnO) and the protective role of Allium sativum (garlic) in male rabbits exposed to ZnO. A daily dose of 30 mg of ZnO and/or 5 g garlic were administered orally to 4 groups of rabbits for 60 days. The first group was used as a control, while the others were used as treatment groups. Biochemical, hepatic, renal, enzymatic, organ weights, and histological parameters were assessed. The results revealed a significant decrease in total bilirubin and triglyceride levels in the group treated with garlic. Cholesterol, uric acid, lactate dehydrogenase, and the relative weight of the liver were non significantly reduced. However, a non significant increase in urea, creatinine, alkaline phosphatase, and the relative weight of the kidney was observed in the garlic treated group. Zinc oxide administration induced a significant decrease in total bilirubin, triglycerides, and alkaline phosphatase levels. The levels of direct bilirubin, cholesterol, urea, creatinine, and lactate dehydrogenase were significantly increased in ZnO treated group compared to the control. The combination of garlic and zinc oxide led to mixed outcomes, with both amelioration and enhancement of certain parameters. Histological examination of the liver and kidney revealed severe morphological and tissue damage in ZnO treated rabbits, whereas co-treatment with garlic reduced tissue damage, indicating partial protection. Overall, these findings suggest that garlic possesses hepatoprotective and nephroprotective properties against zinc- induced toxicity, likely due to its strong antioxidant potential.
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Ahmed M, Laing MD, Nsahlai IV. (2013). In vitro anthelmintic activity of crude extracts of selected medicinal plants against Haemonchus contortus from sheep. Journal of Helminthology 87(2): 174-179. https://doi.org10.1017/S0022149X1200020X
Ahmed RA. (2018). Hepatoprotective and antiapoptotic role of aged black garlic against hepatotoxicity induced by cyclophosphamide. The Journal of Basic and Applied Zoology 79: 8. https://doi.org/10.1186/s41936-018-0017-7
Al-Qattan KK, Thomson M, Al-Mutawa'a S, Al-Hajeri D, Drobiova H, Ali M. (2006). Nitric oxide mediates the blood-pressure lowering effect of garlic in the rat two-kidney, one-clip model of hypertension. Journal of Nutrition 136(3): 774S-776S. https://doi.org/10.1093/jn/136.3.774S
Al-Ragi MJ, Karieb SS, Fathallah N, Zaïri A. (2024). Effect of zinc oxide nanoparticles on liver functions in albino mice. Cureus 16(2): e54822. https://doi.org/10.7759/cureus.54822
Amen MHM, Daraji HJK. (2011). Influence of dietary supplementation with zinc on sex hormones concentrations of broiler breeder chiken. Pakistan Journal of Nutrition 10(11): 1089-1093. https://doi.org/10.3923/pjn.2011.1089.1093
Attal S, Bouchemma F. (2021). Effects of methanol extract of laurel (Laurus nobilis) on lead-induced cytotoxicity in Wistar rats. MSc thesis. University of Frères Mentouri, Constantine 1, Algeria.
Banerjee SK, Maulik M, Manchanda SC, Dinda AK, Das TK, Maulik SK. (2001). Garlic-induced alteration in rat liver and kidney morphology and associated changes in endogenous antioxidant status. Food and Chemical Toxicology 39(8): 793-797. https://doi.org/10.1016/S0278-6915(01)00018-7
Banerjee SK, Maulik SK. (2002). Effect of garlic on cardiovascular disorders : a review. Nutrition Journal 1(4): 1-14. https://doi.org/10.1186/1475-2891-1-4
Bashandy SAE, Ahmed-Farid OAH, Moussa SA, Omara EA, Jaleel GAA, Ibrahim FAA. (2021). Efficacy of zinc oxide nanoparticles on HCC-induced biochemical and trace element alterations in rats. Journal of Applied Pharmaceutical Science 11(05): 108-117. https://doi.org/10.7324/japs.2021.110515
Becker PM, Van Wikselaar PG, Mul MF, Pol A, Engel B, Wijdenes JW, Van der Peet-Schwering CMC, Wisselink HJ, Stockhofe-Zurwieden N. (2012). Actinobacillus pleuropneumoniae is impaired by the garlic volatile allyl methyl sulfide (AMS) in vitro and in-feed garlic alleviates pleuropneumonia in a pig model. Veterinary Microbiology 154(3-4): 316-324. https://doi.org/10.1016/j.vetmic.2011.07.011
Calvo-Gómez O, Morales-López J, López MG. (2004). Solid-phase microextraction-gas chromatographic-mass spectrometric analysis of garlic oil obtained by hydrodistillation. Journal of Chromatography A 1036(1): 91-93. https://doi.org/10.1016/j.chroma.2004.02.072
Chan KC, Yin MC, Chao WJ. (2007). Effect of diallyl trisulfide-rich garlic oil on blood coagulation and plasma activity of anticoagulation factors in rats. Food and Chemical Toxicology 45(3): 502-507. https://doi.org/10.1016/j.fct.2006.10.005
Chidoka CP, Amadikwa UA. (2014). Protective effect of Allium sativa extract against carbon tetrachloride- induced hepatic oxidative stress and hyperlipidemia in rats. African Journal of Biotechnology 13(15): 1671-1678. https://doi.org/10.5897/AJB2013.13338
Chouit Z. (2017). Evaluation and characterization of the neurological, hepatic, and renal risks associated with exposure to heavy metals (lead and cadmium) in the body. University of Mohamed Esseddik Ben Yahia, Jijel, Algeria.
Cruz C, Correa-Rotter R, Sánchez-González DJ, Hernández-Pando R, Maldonado PD, Martínez- Martínez CM, Medina-Campos ON, Tapia E, Aguilar D, Chirino YI, Pedraza-Chaverri J. (2007). Renoprotective and antihypertensive effects of S-allylcysteine in 5/6 nephrectomized rats. American Journal of Physiology - Renal Physiology 293: 1691-1698. https://doi.org/10.1152/ajprenal.00235.2007
Dorrigiv M, Zereiyan A, Hosseinzadeh H. (2020). Garlic (Allium sativum) as an antidote or a protective agent against natural or chemical toxicities : a comprehensive update review. Phytotherapy Research 34(8): 1770-1797. https://doi.org/10.1002/ptr.6645
Dudeja PK, Brasitus TA. (1993). Inactivation of rat small intestinal brush-border membrane alkaline phosphatase by oxygen free radicals. Gastroenterology 105(2): 357-366. https://doi.org/10.1016/0016-5085(93)90708-k
Ejiogu PC. (2024). The effect of garlic formulation on some hematological parameters and organ weight of male and female Wister albino rats. GSC Advanced Research and Reviews 19(02): 104-109. https://doi.org/10.30574/gscarr.2024.19.2.0132
El-mahmood MA. (2009). Efficacy of crude extracts of garlic (Allium sativum Linn) against nosocomial Escherichia coli, Staphylococcus aureus, Streptococcus pneumoniea and Pseudomonas aeruginosa. Journal of Medicinal Plants Research 3(4): 179-185. https://doi.org/10.5897/JMPR.9000547
Farid A, Yousry M, Safwat G. (2022). Garlic (Allium sativum Linnaeus) improved inflammation and reduced cryptosporidiosis burden in immunocompromised mice. Journal of Ethnopharmacology 292: 115174. https://doi.org/10.1016/j.jep.2022.115174
Fischer PW, Giroux A, L’Abbé MR. (1981). The effect of dietary zinc on intestinal copper absorption. The American Journal of Clinical Nutrition 34(9): 1670-1675. https://doi.org/10.1093/ajcn/34.9.1670
Fossati P, Prencipe L. (1982). Serum triglycerides determined colorimetrically with an enzyme that produces hydrogen peroxide. Clinical Chemistry 28(10): 2077-2080. https://doi.org/10.1093/clinchem/28.10.2077
Fossati P, Principe L, Berti G. (1980). Use of 3.5-dichloro-2-hydroxybenzene sulfonic acid / 4 amino phenazone chromogenic system in direct enzymatic assays of uric acid in serum and urine. Clinical Chemistry 26(2): 227-231. https://doi.org/10.1093/clinchem/26.2.227
Gendler S. (1984). Uric acid. In: Kaplan A, Pesce AJ, Kazmierczak SC, editors, Clinical Chemistry. St Louis, MO : CV Mosby. Pp. 1268-1273.
Gorinstein S, Drzewiecki J, Leontowicz H, Leontowicz M, Najman K, Jastrzebski Z, Zachwieja Z, Barton H, Shtabsky B, Katrich E, Trakhtenberg S. (2005). Comparative of the bioactive compounds and antioxidants potentials of fresh and cooked Polish, Ukranian and Israeli garlic. Journal of Agricultural and Food Chemistry 53(7): 2726-2732. https://doi.org/10.1021/jf0404593
Hamdy DA, Ismail MAM, El-Askary HM, Abdel-Baki AS, Al-Quraishy S, Mohamed F, Ahmed MM, Fouad FM, Hassan AO, Abdel-Tawab H. (2024). Green synthesis of zinc oxide/Allium sativum nano-composite and its efficacy against murine cryptosporidiosis. Microscopy Research and Technique 87(8): 1912-1925. https://doi.org/10.1002/jemt.24541
Hamlaoui-Gasmi S, Mokni M, Limam N, N'guessan P, Carrier A, Limam F, Amir M, Aouani E, Marzouki L. (2012). Grape seed and skin extract mitigates garlic-induced oxidative stress in rat liver. Canadian Journal of Physiology and Pharmacology 90(5): 547-556. https://doi.org/10.1139/y2012-025
Harauma A, Moriguchi T. (2006). Aged garlic extract improves blood pressure in spontaneously hypertensive rats more safely than raw garlic. Journal of Nutrition 136: 769S-773S. https://doi.org/10.1093/jn/136.3.769s
Hosseini M, Amani R, Razavimehr V, Moshrefi AH, Aghajanikhah MH. (2018). Histopathologic and biochemical study of zinc oxide nanoparticles effect on renal tissue in rats. Journal of Ilam, University of Medical Sciences 26(3): 177-186. https://doi.org/10.29252/sjimu.26.3.177
Kaplan A, Pesce AJ, Kazmierczak SC. (1984). Bilirubin. In: Kaplan A, Pesce AJ, Kazmierczak SC, editors, Clinical Chemistry. St Louis, MO : CV Mosby. Pp. 1238-1241.
Karale S, Kamath JV. (2017). Protective role of daidzein against cyclophosphamide induced nephrotoxicity in experimental rats. International Journal of Pharmacy and Pharmaceutical Sciences 9(6): 103-107. https://doi.org/10.22159/ijpps.2017v9i6.18516
Khorsandi L, Heidari-Moghadam A, Jozi Z. (2018). Nephrotoxic effects of low-dose zinc oxide nanoparticles in rats. Journal of Nephropathology 7(3): 158-165. https://doi.org/10.15171/jnp.2018.35
Kloucek P, Smid J, Flesar J, Havlik J, Titera D, Rada V, Drabek O, Kokoska L. (2012). In vitro inhibitory activity of essential oil vapors against Ascosphaera apis. Natural Product Communications 7(2): 253-256. https://doi.org/10.1177/1934578x1200700237
Lanzotti V, Barile E, Antignani V, Bonanomi G, Scala F. (2012). Antifungal saponins from bulbs of garlic, Allium sativum L. var. Voghiera. Phytochemistry 78: 126-134. https://doi.org/10.1016/j.phytochem.2012.03.009
Lee TW, Bae E, Kim JH, Jang HN, Cho HS, Chang SH, ParkDJ. (2019). The aqueous extract of aged black garlic ameliorates colistin-induced acute kidney injury in rats. Renal Failure 41(1): 24-33. https://doi.org/10.1080/0886022x.2018.1561375
Leelarungrayub N, RattanapanoneV, Chanarat N, Gebicki JM. (2006).Quantitative evaluation of the antioxidant properties of garlic and shallot preparations. Nutrition 22(3): 266-274. https://doi.org/10.1016/j.nut.2005.05.010
Liu S, Sun Y, Li W, Yu H, Li X, Liu Z, Zeng J, Zhou Y, Chen C, Jia J. (2010). The antibacterial mode of action of allitridi for its potential use as a therapeutic agent against Helicobacter pylori infection. FEMS Microbiology Letters 303(2): 183-189. https://doi.org/10.1111/j.1574-6968.2009.01877.x
Liu S, Zhou H, Shi Y, Yi S, Wang X, Li J, Liao B, Cao J, Li G. (2024). Zinc oxide nanoparticles induce renal injury by initiating oxidative stress, mitochondrial damage and apoptosis in renal tubular epithelial cells. Biological Trace Element Research 202: 481-492. https://doi.org/10.1007/s12011-023-03683-3
Martoja R, Martoja M. (1967). Introduction to animal histology techniques. Paris, France: Masson et Cie.
Mastoor-Tehrani S, Samadian F, Esmaily H, Kargar A, Markazi N, Anvari S, Ziaie S. (2024). The role of zinc supplementation in alleviating inflammatory biomarkers in patients undergoing hemodialysis: a randomized placebo controlled, crossover trial. Iranian Journal of Pharmaceutical Research 23(1): e147887. https://doi.org/10.5812/ijpr-147887
Matcos GG, Rebollar PG, Deblas C. (2010). Minerals, vitamins and additives, the nutrition of the rabbit. CABI publishing, wallingfood 119-150. https://doi.org/10.1079/9781845936693.0119
Meriga B, Mopuri R, Muralikrishna T. (2012). Insecticidal, antimicrobial and antioxidant activities of bulb extracts of Allium sativum. Asian Pacific Journal of Tropical Medicine 5(5): 391-395. https://doi.org/10.1016/s1995-7645(12)60065-0
Murray RL, Kaplan A, Peace AL.(1984). Creatinine. In: Kaplan A, Pesce AJ, Kazmierczak SC, editors, Clinical Chemistry. St Louis, MO : CV Mosby. Pp. 1261-1266.
Naito HK. (1984). Cholesterol. In: Kaplan A, Pesce AJ, Kazmierczak SC, editors, Clinical Chemistry. St Louis, MO : CV Mosby. Pp. 1194-1206.
Nwokocha CR, Ozolua RI, Owu DU, Nwokocha MI, Ugwu AC. (2011). Antihypertensive properties of Allium sativum (garlic) on normotensive and two kidney one clip hypertensive rats. Nigerian Journal of Physiological Sciences 26(2): 213-218. https://pubmed.ncbi.nlm.nih.gov/22547193/
Oyebadejo S, Eno-obong B, Ajayi O, Victor A, Ekaete U. (2014). Histopathological study of the liver of alloxan induced diabetic rats and macerated Allium sativum (garlic) : ameliorative effect. Asian Journal of Biomedical and Pharmaceutical Sciences 04(34): 72-77. https://doi.org/10.15272/ajbps.v4i34.268
Pei X, Jiang H, Xu G, Li C, Li D, Tang S. (2022). Lethality of zinc oxide nanoparticles surpasses conventional zinc oxide via oxidative stress, mitochondrial damage and calcium overload: a comparative hepatotoxicity study. International Journal of Molecular Sciences 23(12): 6724. https://doi.org/10.3390/ijms23126724
Pesce A. (1984). Lactate dehydrogenase. In: In: Kaplan A, Pesce AJ, Kazmierczak SC, editors, Clinical Chemistry. St Louis, MO : CV Mosby. Pp. 1124-117.
Plum LM, Rink L, Haase H. (2010). The essential toxin: impact of zinc on human health. International Journal of Environmental Research and Public Health 7(4): 1342-1365. https://doi.org/10.3390/ijerph7041342
Pundir RK, Jain P, sharma CH. (2010). Antimicrobial activity of ethanolic extracts of Syzygium aromaticum and Allium sativum against food associated bacteria and fungi. Ethnobotanical Leaflets 14(3): 344-360. https://opensiuc.lib.siu.edu/ebl/vol2010/iss3/11
Raguvaran R, Manuja A, Manuja BK. (2015). Zinc oxide nanoparticules: opportunities and challenges in veterinary scienses. Immunome research 11(2): 95. https://doi.org/10.4172/1745-7580.1000095
Rana SV, Pal R, Vaiphei K, Singh K. (2006). Garlic hepatotoxicity: safe dose of garlic. Tropical Gastroenterology 27(1): 26-30. https://pubmed.ncbi.nlm.nih.gov/16910057/
Rosalki SB, Foo AY, Burlina A, Prellwitz W, Stieber P, Neumeier D, Klein G, Poppe WA, Bodenmüller H. (1993). Multicenter evaluation of Iso-ALP test kit for measurement of bone alkaline phosphatase activity in serum and plasma. Clinical Chemistry 39(4): 648-652. https://doi.org/10.1093/clinchem/39.4.648
Sandstead HH. (1995). Requirements and toxicity of essential trace elements, illustrated by zinc and copper. The American Journal of Clinical Nutrition 61(3): 621S-624S. https://doi.org/10.1093/ajcn/61.3.621s
Searcy RL, Reardon JE, Foreman JA. (1967). A new photometric method for serum urea nitrogen determination. American Journal of Medical Technology 33(1): 15-20. https://pubmed.ncbi.nlm.nih.gov/6037908/
Sener G, Sakarcan A, Yegen BC. (2007). Role of garlic in the prevention of ischemia-reperfusion injury. Molecular Nutrition and Food Research 51(11): 1345-1352. https://doi.org/10.1002/mnfr.200700078
Sengupta A, Ghosh S, Bhattacharjee S. (2004). Allium vegetables in cancer prevention: an overview. Asian Pacific Journal of Cancer Prevention 5(3): 237-245. https://pubmed.ncbi.nlm.nih.gov/15373701/
Shang A, Cao S, Xu X, Gan R, Tang G, Corke H, Mavumengwana V, Li H. (2019). Bioactive compounds and biological functions of garlic (Allium sativum L.). Foods 8(7): 246. https://doi.org/10.3390/foods8070246
Sheir MA, Almaski AM, Almughamisi MA, Abduljawad SH, Elsebaie EM, Ahmed RA. (2025). Nephroprotective effect of aged black garlic extract as a functional flock medicinal on sodium benzoate-induced chronic kidney disease in albino rats. Life 15(2): 217. https://doi.org/10.3390/life15020217
Singh P, Singh J, Singh S, Singh BR. (2014). Medicinal values of garlic (Allium sativum L.) in human life: an overview. Greener Journal of Agricultural Sciences 4(6): 265-280. http://dx.doi.org/10.15580/gjas.2014.6.031914151
Singh TU, Kumar D, Tandan SK, Mishra SK. (2009). Inhibitory effect of essential oils of Allium sativum and Piper longum on spontaneous muscular activity of liver fluke, Fasciola gigantica. Experimental Parasitology 123(4): 302-308. https://doi.org/10.1016/j.exppara.2009.08.002
Sok DE. (1999). Oxidative inactivation of brain alkaline phosphatase responsible for hydrolysis of phosphocholine. Journal of Neurochemistry 72(1): 355-362. https://doi.org/10.1046/j.1471-4159.1999.0720355.x
Stohs SJ, Bagchi D. (1995). Oxidative mechanisms in the toxicity of metal ions. Free Radical Biology and Medicine 18(2): 321-336. https://doi.org/10.1016/0891-5849(94)00159-H
Suriyavadhana M, Pakutharivu T. (2011). Evaluation of acute and sub acute toxicity of ethanol extracts of Entada pursaetha, Toddalia aculeata, and Ziziphus mauritiana. World Journal of Life Sciences and Medical Research 1(2): 43-47.
Tandon SK, Shibbu Singh S, Prasad S. (2008). Influence of garlic on the disposition and toxicity of lead and cadmium in the rat. Pharmaceutical Biology 39(6): 450-454. https://doi.org/10.1076/phbi.39.6.450.5887
Tugbobo OS, Ologunde CA, Orji EE. (2016). Anticlastogenic effect of Allium sativum extract against lead-induced necrosis in liver and kidney of albino rats. Asian Journal of Plant Science and Research 6(4): 1-5. https://hal.science/hal-03641007v1
Verma T, Manish S, Nitin B, Shyam RY, Kamal S, Nagendra SC. (2021). Review: plants used as antihypertensive. Natural Products and Bioprospecting 11(2): 155-184. https://doi.org/10.1007/s13659-020-00281-x
Wang KK, Cui HW, Sun JY, Qian LC, Weng X. (2012). Effect of zinc on growth performance and biochemical parameters of piglets. Turkish Journal of Veterinary and Animal Scienses 36(5): 519-526. https://doi.org/10.3906/vet-1010-553
Wei C, Luo Z, Hogstrand C, Xu Y, Wu L, Chen G, Pan Y, Song Y. (2018). Zinc reduces hepatic lipid deposition and activates lipophagy via Zn2+/MTF-1/PPARα and Ca2+/CaMKKβ/AMPK pathways. The FASEB Journal 32(12): 6666-6680. https://doi.org/10.1096/fj.201800463
Xu YC, Zheng H, Hogstrand C, Tan XY, Zhao T, Song YF, Wei XL, Wu LX, Luo Z. (2023). Novel mechanism for zinc inducing hepatic lipolysis via the HDAC3-mediated deacetylation of β-catenin at lysine 311. Journal of Nutritional Biochemistry 121: 109429. https://doi.org/10.1016/j.jnutbio.2023.109429
Yanagisawa H. (2008). Zinc deficiency and clinical practice validity of zinc preparations. Yakugaku Zasshi 128(3): 333-339. https://doi.org/10.1248/yakushi.128.333
Yanagisawa H, Miyazaki T, Nodera M, Miyajima Y, Suzuki T, Kido T. (2014). Zinc-excess intake causes the deterioration of renal function accompanied by an elevation in systemic blood pressure primarily through superoxide radical-induced oxidative stress. International Journal of Toxicology 33(4): 288-296. https://doi.org/10.1177/1091581814532958
Yang Q, Qian L, He S, Zhang C. (2024). Hesperidin alleviates zinc-induced nephrotoxicity via the gut-kidney axis in swine. Frontiers in Cellular and Infection Microbiology 14: 1390104. https://doi.org/10.3389/fcimb.2024.1390104
Yang T, Richards EM, Pepine CJ, Raizada MK. (2018). The gut microbiota and the brain-gut-kidney axis in hypertension and chronic kidney disease. Nature Reviews Nephrology 14: 442-456. https://doi.org/10.1038/s41581-018-0018-2
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