Ameliorative effects of the ethanolic extract of Allium saralicum R.M. Fritsch on CCl4-induced nephrotoxicity in mice: A stereological examination

Hamidreza Sherkatolabbasieh, Lida Hagh-Nazari, Shiva Shafiezadeh, Nader Goodarzi, Mohammad Mehdi Zangeneh, Akram Zangeneh


The present study was carried out to investigate the nephroprotective effect of the ethanolic extract of Allium saralicum R.M. Fritsch (ASRMF) in mice. Thirty-five male mice were divided into five groups (n=7). Group 1 (positive control) received 1 mL/kg olive oil intraperitoneally (i.p.) and 0.5 mL distilled water orally; Group 2 (negative control) received CCl4 (50% in olive oil, 1 mg/kg; i.p.); Groups 3, 4 and 5 received CCl4 and 200, 800 and 1600 µg/kg of ASRMF extract, respectively. The renal volume and cortex in Groups 1 and 2 were increased by 55% and 62% (p≤0.001) following CCl4 administration, respectively, and were improved after ASRMF administration. The volume of proximal convoluted tubules (PCTs), glomeruli, vessels and interstitial tissue increased 80%, 150%, 83% and 64% (p≤0.05), respectively, in CCl4-treated mice, and decreased significantly with 800 and 1600 µg/kg of ASRMF. The length of PCTs and vessels increased 51% and 45% and decreased (p≤0.05) with 200, 800 and 1600 µg/kg of ASRMF, respectively. CCl4-treated mice lost 22.5% of glomeruli; the loss was inhibited significantly (p≤0.05) by ASRMF. Urea and creatinine concentrations were increased (p≤0.05) in CCl4-induced nephrotoxicity as compared to the controls, whereas different doses of ASRMF restored the levels of these biomarkers compared to the negative controls. In conclusion, ASRMF has a potent nephroprotective property and can improve renal structural and serum biomarkers in CCl4-induced nephrotoxicity in mice.

Received: September 14, 2016; Revised: November 18, 2016; Accepted: November 21, 2016; Published online: November 28, 2016

How to cite: Sherkatolabbasieh H, Hagh-Nazari L, Shafiezadeh S, Goodarzi N, Zangeneh MM, Zangeneh A. Ameliorative effects of the ethanolic extract of Allium saralicum R.M. Fritsch on CCl4-induced nephrotoxicity in mice: A stereological examination. Arch Biol Sci. 2017;69(3):535-43.


carbon tetrachloride; Allium saralicum; kidney; nephrotoxicity; stereology

Full Text:



Abraham P, Wilfred G, Cathrine SP. Oxidative damage to the lipids and proteins of the lungs, testis and kidney of rats during carbon tetrachloride intoxication. Clin Chim Acta. 1999;289:177-9.

Rechnagel RO, Glende EA, Dolak JA, Waller RL. Mechanisms of carbon tetrachloride toxicity. J Pharmacol Exp Ther. 1989;43:139-54.

Kumar G, Banu GS, Pandian MR. Evaluation of the antioxidant activity of Trianthemaportula castrum L. Ind J Pharmacol. 2005;37:331-3.

Khan MR, Ahmed D. Protective effects of Digeramuricata (L.) Mart. on testis against oxidative stress of carbon tetrachloride in rat. Food Chem Toxicol. 2009;47:1393-99.

Khan MR, Rizvi W, Khan GN, Khan RA, Shaheen S. Carbon tetrachloride induced nephrotoxicity in rat: protective role of Diger amuricata. J Ethnopharmacol. 2009;122:91-9.

Slater TF. Free radical mechanisms in tissue injury. Biochem J. 1984;222:1-15.

Halliwell B, Gutteridge J. Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem J. 1984;219:1-14.

Halliwell B, Gutteridge JMC. Cellular responses to oxidative stress: adaptation, damage, repair, senescence and death. In: Halliwell B, Gutteridge JMC, editors. Free Radicals in Biology and Medicine. Oxford: Oxford University Press Inc; 2007. 187-267 p.

Satyanarayana. PS, Singh D, Chopra K. Quercetin, a biflavonoid, protects against oxidative stress-related renal dysfunction by cyclosporine in rats. Methods Find Exp Clin Pharmacol. 2001;23:175-81.

Manna P, Mahua S, Parames CS. Aqueous extract of Terminalia arjuna prevents carbon tetrachloride-induced hepatic and renal disorders. BMC Complement Altern Med. 2006;6:33.

Adewole SO, Salako AA, Doherty OW, Naicker T. Effect of melatonin on carbon tetrachloride-induced kidney injury in Wistar rats. Afr J Biomed Res. 2007;10:153-64.

Perez AJ, Courel M, Sobrado J, Gonzalez L. Acute renal failure by tropical application of carbon tetrachloride. Lancet. 1987;1:515-6.

Ko KM, Ip SP, Poon MK, Wu SS, Che CT, Ng KH, Kong YC. Effect of a lignan-enriched Fructus schisandrae extract on hepatic glutathione status in rats: protection against carbon tetrachloride toxicity. Planta Medica. 1995;61:134-7.

Rajesh MG, Latha M.S. Protective activity of Glycyrrhizaglabra Linn. on carbon tetrachloride-induced peroxidative damage. Indian J Pharmacol. 2004;36:284-7.

Block E. Garlic and Other Alliums: The Lore and the Science. Cambridge: Royal Society of Chemistry; 2010. 121 p.

Davies D. Alliums: The Ornamental Onions. Portland: Timber Press; 1992. 58 p.

National Research Council (NRC) [Internet]. Guide for the Care and Use of Laboratory Animals. Washington: National Academy of Sciences; 1996 [cited 2016 Nov 21]. Available from:

Silva MA, Merzel J. Stereological determination of the volume of the rat hemimandible tissues. Anat Rec. 2001;263:255-9.

Gundersen, HJ, Bendtsen TF, Korbo L, Marcussen N, Møller A, Nielsen K. Some new, simple and efficient stereological methods and their use in pathological research and diagnosis. APMIS. 1988;96:379-94.

Braendgaard H, Gundersen HJ. The impact of recent stereological advances on quantitative studies of the nervous system. J Neurosci Methods. 1986;18:39-78.

Nyengaard JR. Stereologic methods and their application in kidney research. J Am Soc Nephrol. 1999;10(5):1100-23.

Mandarim-de-Lacerda CA. Stereological tools in biomedical research. An Acad Bras Cienc. 2003;75(4):469-86.

Sterio DC. The unbiased estimation of number and sizes of arbitrary particles using the dissector. J Microsc. 1984;134:127-36.

Thrall KD, Vucelick ME, Gies RA. Comparative metabolism of carbon tetrachloride in rats, mice, and hamsters using gas uptake and PBPK modeling. J Toxicol Environ Health. 2000;60:531-48.

Ohta Y, Kongo M, Sasaki E, Nishida K, Ishiguro I. Therapeutic effect of melatonin on carbon tetrachloride-induced acute liver injury in rats. J Pineal Res. 2000;28:119-26.

Naziroglu M, Cay M, Ustundag B, Aksakal M, Yekeler H. Protective effects of vitamin E on carbon tetrachloride-induced liver damage in rats. Cell Biochem Funct. 1999;17:253-9.

Mukai T, Mera K, Nishida K. A novel method for preparation of animal models of liver damage: liver targeting of carbon tetrachloride in rats. Biol Pharm Bull. 2002;25:1494-7.

Sanzgiri UY, Srivatsan V, Muralidhara S, Dallas CE, Bruckner JV. Uptake, distribution, and elimination of carbon tetrachloride in rat tissues following inhalation and ingestion exposures. Toxicol Appl Pharmacol. 1997;143:120-9.

Ronis M.J, Huang J, Longo V, Tindberg N, Ingelman-Sundberg M, Badger TM. Expression and distribution of cytochrome P450 enzymes in male rat kidney: Effects of ethanol, acetone and dietary conditions. Biochem Pharmacol. 1998;55:123-9.

Rush GF, Smith JH, Newton JF, Hook JB. Chemically induced nephrotoxicity: role of metabolic activation. Crit Rev Toxicol. 1984;13:99-160.

Chaiyasut C, Kusirisin W, Lailerd N, Lerttrakarnnon P, Suttajit M, Srichairatanakool S. Effects of phenolic compounds of fermented Thai indigenous plants on oxidative stress in streptozotocin-induced diabetic rats. J Evid Based Complementary Altern Med. 2011;2011:1-10.

Priyadarshini M,Aatif M, Bano B. Alpha-linolenic acid protects against gentamicin induced toxicity. Res Report Biochem. 2012;2:25-9.

Ren J, Chung SH. Anti-inflammatory effect of α-linolenic acid and its mode of action through the inhibition of nitric oxide production and inducible nitric oxide synthase gene expression via NF-κB and mitogen-activated protein kinase pathways. J Agric Food Chem.2007;55:5073-80.

Rajeswari G, Murugan M, Mohan VR. GC-MS analysis of bioactive components of Hugoniamystax L. (Linaceae). Res J Pharm Biol Chem Sci. 2012;3:301-8.

Lin HM, Tseng HC, Wang CJ, Lin JJ, Lo CW, Chou FP. Hepatoprotective effects of Solanum nigrum Linn. extract against CCl4-induced oxidative damage in rats. Chem Biol Interact. 2008;171:283-93.

Striker GE, Smockler EA, Kohnen PW, Nagle RB. Structural and functional changes in rat kidney during CCl4intoxication. Am J Pathol. 1968;53:769-89.

Khan M.R, Zehra, H. Amelioration of CCl4-induced nephrotoxicity by Oxalis corniculata in rat. Exp Toxicol Pathol. 2013;65:327-34.

Khan M.R, Siddigue F. Antioxidant effects of Citharexylum spinosum in CCl4 induced nephrotoxicity in rat. Exp Toxicol Pathol. 2012;64:349-55.

Khan RA, Khan MR. Prevention of CCl4-induced nephrotoxicity with Sonchus asper in rat. Food Chem Toxicol. 2010;48:2469-76.

Laurinavicius A, Laurinaviciene A, Dasevicius D, Elie N, Plancoulaine B, Herlin P. Digital image analysis in pathology: Benefits and obligation. Anal Cell Pathol. 2012;35:75-8.

Pantanowitz L. Digital images and the future of digital pathology. J Pathol Inform. 2010;1:15.

Klapczynski M, Gagne GD, Morgan SJ, Larson KJ, LeRoy BE, Blomme EA, Cox BF, Shek E W. Computer-assisted imaging algorithms facilitate histomorphometric quantification of kidney damage in rodent renal failure models. J Pathol Inform. 2012;3:20.

Boyce JT, Boyce RW, Gundersen HJ. Choice of morphometric methods and consequences in the regulatory environment. Toxicol Pathol. 2010;38:1128-33.


  • There are currently no refbacks.


Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.