Effects of Silybum marianum Aqueous Extract and L-carnitine on Stereological Changes in Diazinon-Treated Rat Liver

Forough Masoumi, Mehrdad Shariati, Mokhtar Mokhtari


As an organophosphorus, Diazinon (DZN) impairs liver tissue function by inhibiting acetylcholinesterase and causing oxidative stress. In this study, the effects of Silybum marianum aqueous extract (SMAE) and L-carnitine (LC) on the stereological and histopathological changes of the liver in DZN-treated male rats were investigated. The rats in this study were placed into 9 groups of 8 each containing control, placebo, and a combination of DZN, SMAE, and LC. The animals received SMAE and chemicals orally for 30 days. At last, the liver tissue of all animals was removed. Then, tissue sections from the liver were provided to study the stereological markers including liver volume and weight, hepatocytes’ volume, central venous volume, sinusoidal volume, connective tissue volume, inflammation rate, and a number of the hepatocytes’ nuclei. Also, the sample tissues were evaluated histopathologically. Treatment with DZN significantly reduced the liver volume and weight, hepatocyte volume, central venous volume, sinusoidal volume, and hepatocyte nucleus number compared to placebo and control but it significantly increased the inflammation and volume of liver’s connective tissue. However, co-administration of SMAE and LC with DZN improved liver volume and weight, hepatocyte volume, central venous volume, sinusoidal volume, connective tissue volume, and hepatocyte nucleus number alone compared to the DZN treatment. Liver inflammation was also significantly decreased compared to the DZN treatment but comparing to the placebo and control groups, it increased significantly. Simultaneous administration of SMAE and LC has protective effects on liver tissue and can reduce DZN-induced liver injury in rats.


Diazinon, L-carnitine, Liver, Rat, Silybum marianum

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Abdel-Daim MM, Taha R, Ghazy EW, El-Sayed YS. 2016. Synergistic ameliorative effects of sesame oil and alpha-lipoic acid against subacute diazinon toxicity in rats: hematological, biochemical, and antioxidant studies. Can J Physiol Pharmacol 94:81–88.

Abenavoli L, Izzo AA, Milić N, Cicala C, Santini A, Capasso R. 2018. Milk thistle (Silybum marianum): A concise overview on its chemistry, pharmacological, and nutraceutical uses in liver diseases. Phyther Res. 32:2202–2213.

Anbarkeh FR, Nikravesh MR, Jalali M, Sadeghnia HR, Sargazi Z, Mohammdzadeh L. 2014. Single dose effect of diazinon on biochemical parameters in testis tissue of adult rats and the protective effect of vitamin E. Iran J Reprod Med. 12:731–736.

Beydilli H, Yilmaz N, Cetin ES, Topal Y, Celik OI, Sahin C, Topal H, Cigerci IH, Sozen H. 2015. Evaluation of the protective effect of silibinin against diazinon induced hepatotoxicity and free-radical damage in rat liver. Iran Red Crescent Med J. 17:1–7.

Bijak M. 2017. Silybin, a major bioactive component of milk thistle (Silybum marianum L. Gaernt.)—chemistry, bioavailability, and metabolism. Molecules. 22:1942.

Duysen EG, Cashman JR, Schopfer LM, Nachon F, Masson P, Lockridge O. 2012. Differential sensitivity of plasma carboxylesterase-null mice to parathion, chlorpyrifos and chlorpyrifos oxon, but not to diazinon, dichlorvos, diisopropylfluorophosphate, cresyl saligenin phosphate, cyclosarin thiocholine, tabun thiocholine, and carbofu. Chem Biol Interact. 195:189–198.

Eroglu S, Pandir D, Uzun FG, Bas H. 2013. Protective role of vitamins C and E in diclorvos-induced oxidative stress in human erythrocytes in vitro. Biol Res. 46:33–38.

Ghoreyshi S, Omri B, Chalghoumi R, Bouyeh M, Seidavi A, Dadashbeiki M, Lucarini M, Durazzo A, van den Hoven R, Santini A. 2019. Effects of dietary supplementation of L-carnitine and excess lysine-methionine on growth performance, carcass characteristics, and immunity markers of broiler chicken. Animals. 9:362.

Hodges RE, Minich DM. 2015. Modulation of metabolic detoxification pathways using foods and food-derived components: a scientific review with clinical application. J Nutr Metab. 2015:1–23.

Hussei AS, Abd El- OM, Hemdan HS. 2014. Protective effect of L-carnitine on metabolic disorders, oxidative stress, antioxidant status and inflammation in a rat model of insulin resistance. Int J Biol Chem. 8:21–36.

Jones RR, Barone-Adesi F, Koutros S, Lerro CC, Blair A, Lubin J, Heltshe SL, Hoppin JA, Alavanja MCR, Beane Freeman LE. 2015. Incidence of solid tumours among pesticide applicators exposed to the organophosphate insecticide diazinon in the Agricultural Health Study: an updated analysis. Occup Environ Med. 72:496–503.

Karimi A, Majlesi M, Rafieian-Kopaei M. 2015. Herbal versus synthetic drugs; beliefs and facts. J nephropharmacology. 4:27–30.

Li D, Huang Q, Lu M, Zhang L, Yang Z, Zong M, Tao L. 2015. The organophosphate insecticide chlorpyrifos confers its genotoxic effects by inducing DNA damage and cell apoptosis. Chemosphere. 135:387–393.

Messarah M, Amamra W, Boumendjel A, Barkat L, Bouasla I, Abdennour C, Boulakoud MS, Feki A El. 2013. Ameliorating effects of curcumin and vitamin E on diazinon-induced oxidative damage in rat liver and erythrocytes. Toxicol Ind Health. 29:77–88.

Murali P, George SK, Ally K, Dipu MT. 2015. Effect of L-carnitine supplementation on growth performance, nutrient utilization, and nitrogen balance of broilers fed with animal fat. Vet World. 8:482–486.

Nasri H. 2013. Renoprotective effects of garlic. J Ren Inj Prev. 2:27–28.

Negahdary M, Bezhgi M, Ajdary M. 2015. Effects of Silymarin on Oxidative Stress Markers in Rats Treated with Magnesium Oxide Nanoparticles. Annu Res Rev Biol. 5:254–261.

Newcomb RD, Gleeson DM, Yong CG, Russell RJ, Oakeshott JG. 2005. Multiple mutations and gene duplications conferring organophosphorus insecticide resistance have been selected at the Rop-1 locus of the sheep blowfly, Lucilia cuprina. J Mol Evol. 60:207–220.

Pearson JN, Patel M. 2016. The role of oxidative stress in organophosphate and nerve agent toxicity. Ann N Y Acad Sci. 1378:17–24.

Prokić M, Borković-Mitić S, Krizmanić I, Gavrić J, Despotović S, Gavrilović B, Radovanović T, Pavlović S, Saičić Z. 2017. Comparative study of oxidative stress parameters and acetylcholinesterase activity in the liver

of Pelophylax esculentus complex frogs. Saudi J Biol Sci. 24:51–58.

Sajadi SM, Nasrollahzadeh M, Maham M. 2016. Aqueous extract from seeds of Silybum marianum L. as a green material for preparation of the Cu/Fe3O4 nanoparticles: A magnetically recoverable and reusable catalyst for the reduction of nitroarenes. J Colloid Interface Sci. 469:93–98.

Scherle W. 1970. A simple method for volumetry of organs in quantitative stereology. Mikroskopie. 26:57–60.

Slotkin TA, Seidler FJ. 2012. Developmental neurotoxicity of organophosphates targets cell cycle and apoptosis, revealed by transcriptional profiles in vivo and in vitro. Neurotoxicol Teratol. 34:232–241.

Soto-Méndez MJ, Aguilera CM, Mesa MD, Campaña-Martín L, Martín-Laguna V, Solomons NW, Schümann K, Gil Á. 2016. Strong associations exist among oxidative stress and antioxidant biomarkers in the circulating, cellular and urinary anatomical compartments in Guatemalan children from the Western Highlands. Vrana KE, editor. PLoS One. 11:e0146921.

Surai P. 2015. Silymarin as a Natural Antioxidant: An Overview of the Current Evidence and Perspectives. Antioxidants. 4:204–247.

Trefts E, Gannon M, Wasserman DH. 2017. The liver. Curr Biol. 27:R1147–R1151.

Valko M, Jomova K, Rhodes CJ, Kuča K, Musílek K. 2016. Redox- and non-redox-metal-induced formation of free radicals and their role in human disease. Arch Toxicol. 90:1–37.

Xiong F, Guan Y-S. 2017. Cautiously using natural medicine to treat liver problems. World J Gastroenterol. 23:3388–3395.

Zahkouk SA, El-Gendy AM, Eid FA, El-Tahway NA, El-Shamy SA. 2015. Physiological and Histological Studies on the Heart of Male Albino Rats Exposed to Electromagnetic Field and the Protective Role of Silymarin and/Orvitamin E. Egypt J Hosp Med. 58:94–108.

Zare S, Hossein Dabbaghmanesh M, Noorafshan A, Koohpeyma F, Bakhshayeshkaram M, Montazeri-Najafabady N. 2019. Protective effect of vitamin E and vitamin C alone and in combination on testicular damage induced by sodium metabisulphite in rats: A stereological study. Andrologia. 51:e13193.


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