Veterinary Research Forum
Vet Res Forum

Silymarin protects the structure of kidney in the neonatal rats exposed to maternal cadmium toxicity: A stereological study

Document Type : Original Article

Authors

Gholamreza Hamidian 1
Shadmehr Mirdar 2
Pourya Raee 1, 1, 3
Kiyana Asghari 1
Maryam Jarrahi 2

1 Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran

2 Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, University of Mazandaran, Babolsar, Iran

3 Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

https://doi.org/10.30466/vrf.2019.84202.2108
Abstract
The present study aimed to investigate the protective effect of silymarin on maternal cadmium toxicity complications in the kidney of neonatal rats. Forty adults Wistar female rats were selected and placed with male rats for copulation. The pregnant animals were randomly divided into five groups (n = 8) including control, sham, silymarin, cadmium, and silymarin + cadmium. The animals received 400 mg L-1 cadmium and 100 mg kg-1 silymarin (sub-cutaneously, three days per week, three weeks). Two-day neonates were dissected and their right kidneys were fixed in 10.00% buffered formalin solution and processed by standard paraffin embedding. Tissue sections were stained by hematoxylin and eosin and analyzed histologically and stereologically. The data were statistically analyzed by SPSS using a one-way ANOVA test and Tukey's post-hoc. The results showed that silymarin significantly increased the neonatal rats' weight compared to the control group. Cadmium significantly decreased the weight of neonatal rats' kidneys. The results of histological studies indicated that cadmium caused subacute glomerulosclerosis, severe damage to urinary tubules such as tubular necrosis, and severe hyperemia in the medulla, but silymarin could preserve these complications. Stereological results revealed that cadmium decreased the total volume of kidney, medulla, and proximal and distal tubules and increased interstitial tissue and indicated the protective effects of silymarin on maternal cadmium toxicity complications in the kidney tissue of neonatal rats. It can be concluded that the administration of silymarin during pregnancy may be used as a useful and effective way of protecting the maternal cadmium toxicity complications in the kidney tissue of neonatal rats.

Keywords

Cadmium
Kidney
Rat
Silymarin
Stereology

  1.  

    1. Kaur S, Sharma S. Assessment of biochemical alterations induced by acute and chronic doses of cadmium in albino mice. Asian J Pharmacol Toxicol 2015; 3(7): 1-4.
    2. Kostial K, Kello D, Jugo S, et al. Influence of age on metal metabolism and toxicity. Environ Health Perspect 1978; 25: 81-86.
    3. Korpela H, Loueniva R, Yrjänheikki E, et al. Lead and cadmium concentrations in maternal and umbilical cord blood, amniotic fluid, placenta, and amniotic membranes. Am J Obstet Gynecol 1986; 155(5): 1086-1089.
    4. Sarkar A, Ravindran G, Krishnamurthy V. A brief review on the effect of cadmium toxicity: From cellular to organ level. Int J Biotechnol Res 2013; 3(1): 17-36.
    5. Zhai Q, Tian F, Zhao J, et al. Oral administration of probiotics inhibits absorption of the heavy metal cadmium by protecting the intestinal barrier. Appl Environ Microbiol 2016; 82(14): 4429-4440.
    6. Matović V, Buha A, Ðukić-Ćosić D, et al. Insight into the oxidative stress induced by lead and/or cadmium in blood, liver and kidneys. Food Chem Toxicol 2015; 78: 130-140.
    7. El-Refaiy AI, Eissa FI. Histopathology and cytotoxicity as biomarkers in treated rats with cadmium and some therapeutic agents. Saudi J Biol Sci 2013; 20(3): 265-280.
    8. Yang H, Shu Y. Cadmium transporters in the kidney and cadmium-induced nephrotoxicity. Int J Mol Sci 2015; 16(1): 1484-1494.
    9. Druet P, Bernard A, Hirsch F, et al. Immunologically mediated glomerulonephritis induced by heavy metals. Arch Toxicol 1982; 50: 187-194.
    10. Coccini T, Barni S, Manzo L, et al. Apoptosis induction and histological changes in rat kidney following Cd-doped silica nanoparticle exposure: evidence of persisting effects. Toxicol Mech Methods 2013; 23(8): 566-575.
    11. Luo T, Liu G, Long M, et al. Treatment of cadmium-induced renal oxidative damage in rats by ‎administration of alpha-lipoic acid. Environ Sci Pollut Res Int 2017; 24(2): 1832-1844.‎
    12. Prozialeck WC. Evidence that E-cadherin may be a target for cadmium toxicity in epithelial cells. Toxicol Appl Pharmacol 2000; 164(3): 231-249.
    13. Elinder CG, Lind B, Kjellström T, et al. Cadmium in kidney cortex, liver, and pancreas from Swedish autopsies. Estimation of biological half time in kidney cortex, considering calorie intake and smoking habits. Arch Environ Health 1976; 31(6): 292-302.
    14. Il'yasova D, Schwartz GG. Cadmium and renal cancer. Toxicol Appl Pharmacol 2005; 207(2): 179-186.
    15. Nishijo M, Nakagawa H, Honda R, et al. Effects of maternal exposure to cadmium on pregnancy outcome and breast milk. Occup Environ Med 2002; 59(6): 394-397.
    16. Abouzeinab NS. Antioxidant effect of silymarin on cisplatin-induced renal oxidative stress in rats. J Pharmacol Toxicol 2015; 10(1): 1-19.
    17. Poppe L, Petersen M. Variation in the flavonolignan composition of fruits from different Silybum marianum chemotypes and suspension cultures derived therefrom. Phytochemistry 2016; 131: 68-75.
    18. Surai PF. Silymarin as a natural antioxidant: An overview of the current evidence and perspectives. Antioxidants (Basel) 2015; 4(1): 204-247.
    19. Hamidian Gh, Alboghobeish N, Najafzadeh Varzi H, et al. Unbiased stereological and histological study of silymarin effects on hamster adrenocortical structure in response to an exogenous glucocorticoid. J Cell Anim Biol 2009; 3(7): 107-112.
    20. Fraschini F, Demartini G, Esposti D. Pharmacology of silymarin. Clin Drug Investig 2002; 22: 51-65.
    21. Shahbazi F, Dashti-Khavidaki S, Khalili H, et al. Potential renoprotective effects of silymarin against nephrotoxic drugs: A review of literature. J Pharm Pharm Sci 2012; 15(1): 112-123.
    22. El-Khishin IA, El-Fakharany YMM, Abdel Hamid OI. Role of garlic extract and silymarin compared to dimercaptosuccinic acid (DMSA) in treatment of lead induced nephropathy in adult male albino rats. Toxicol Rep 2015; 2: 824-832.
    23. Khodeary MF, Sharaf El-Din AAI, El Kholy SMS, et al. Potential ameliorative role of silymarin against methyl parathion-induced oxidative stress and hepato-renal toxicity in albino rats. Mansoura J Forensic Med Clin Toxicol 2009; 17(1): 15-40.
    24. La Grange L, Wang M, Watkins R, et al. Protective effects of the flavonoid mixture, silymarin, on fetal rat brain and liver. J Ethnopharmacol 1999; 65(1): 53-61.
    25. Barański B, Stetkiewicz I, Trzcinka-Ochocka M, et al. Teratogenicity, fetal toxicity and tissue concentration of cadmium administered to female rats during organogenesis. J Appl Toxicol 1982; 2(5): 255-259.
    26. Nyengaard JR. Stereologic methods and their application in kidney research. J Am Soc Nephrol ‎‎1999; 10(5): 1100-1123.‎
    27. Howard C, Reed M. Unbiased stereology: Three-dimensional measurement in microscopy, Oxford, UK. Bios Scientific Publishers; 1998: 39-54.
    28. Pazvant G, Sahin B, Kahvecioglu KO, et al. The volume fraction method for the evaluation of kidney: A stereo-logical study. Vet Fak Derg 2009: 56(4): 233-239.
    29. Nyengaard JR, Flyvbjerg A, Rasch R. The impact of renal growth, regression and regrowth in experimental diabetes mellitus on number and size of proximal and distal tubular cells in the rat kidney. Diabetologia 1993; 36: 1126-1131.
    30. Gundersen HJ, Jensen EB, Kiêu K, et al. The efficiency of systematic sampling in stereology-reconsidered. J Microsc 1999; 193(Pt3): 199-211.
    31. Bernhoft RA. Cadmium toxicity and treatment. Sci World J 2013; 394652. doi: 10.1155/2013/394652.
    32. Babaei Zarch A, Fallah Huseini H, Kianbakht S, et al. Effects of silymarin on cadmium-induced toxicity in rats. J Med Plants 2012; 11(43): 90-96.
    33. Sharma B, Singh S, Siddiqi NJ. Biomedical implications of heavy metals induced imbalances in redox systems.BioMed Res Int 2014; 640754. doi: 10.1155/2014/ 640754.
    34. Sabath E, Robles-Osorio ML. Renal health and the environment: Heavy metal nephrotoxicity. Nefrologia 2012; 32(3): 279-286.
    35. Sonawane BR, Nordberg M, Nordberg GF, et al. Placental transfer of cadmium in rats: Influence of dose and gestational age. Environ Health Perspect 1975; 12: 97-102.
    36. Reyes JL, Molina-Jijón E, Rodríguez-Muñoz R, et al. Tight junction proteins and oxidative stress in heavy metals-induced nephrotoxicity. Biomed Res Int 2013; 730789. doi: 10.1155/2013/730789.
    37. Prozialeck WC, Edwards JR. Mechanisms of cadmium-induced proximal tubule injury: New insights with implications for biomonitoring and therapeutic interventions. J Pharmacol Exp Ther 2012; 343(1): 2-12.
    38. Nair AR, Degheselle O, Smeets K, et al. Cadmium-induced pathologies: Where is the oxidative balance lost (or not)? Int J Mol Sci 2013; 14(3): 6116-6143.
    39. Johnston JE, Valentiner E, Maxson P, et al. Maternal cadmium levels during pregnancy associated with lower birth weight in infants in a North Carolina cohort. PLoS One 2014; 9: e109661. doi: 10.1371/ journal.pone.0109661.
    40. Rafati A, Hoseini L, Babai A, et al. Mitigating effect of resveratrol on the structural changes of mice liver and kidney induced by cadmium; A stereological study.Prev Nutr Food Sci 2015; 20(4): 266-275
    41. Dorian C, Gattone VH 2nd, Klaassen CD. Discrepancy between the nephrotoxic potencies of cadmium-metallothionein and cadmium chloride and the renal concentration of cadmium in the proximal convoluted tubules.Toxicol Appl Pharmacol 1995; 130(1): 161-168.
    42. Amien AI, Fahmy SR, Abd-Elgleel FM, et al. Renoprotective effect of Mangifera indica poly-saccharides and silymarin against cyclophosphamide toxicity in rats. J Basic Appl Zool 2015; 72: 154-162.
    43. Kaur AK, Wahi AK, Kumar B, et al. Milk thistle (Silybum marianum): A review. Int J Pharm Res Dev 2011; 3 :1-10.
    44. Adnan A, Bilge O, Sahin K, et al. The protective effect of silymarin on the antioxidant system at rat renal ischemia/reperfusion injury model. Afr J Pharm Pharmacol 2013; 7(6): 220-226.
    45. Radko L, Cybulski W. Application of silymarin in human and animal medicine. J PreClin Clin Res 2007; 1(1): 22-26.
    46. Tantituvanont A, Jiamchaisri P, Chunhacha P, et al. Silymarin inhibits cisplatin-mediated apoptosis via inhibition of hydrogen peroxide and hydroxyl radical generation. Songklanakarin J Sci Technol 2015; 37(2): 155-162.
    47. Karimi G, Vahabzadeh M, Lari P, et al. Silymarin, a promising pharmacological agent for treatment of diseases.Iran J Basic Med Sci 2011; 14(4): 308-317.
    48. Chtourou Y, Garoui el M, Boudawara T, et al. Protective role of silymarin against manganese-induced nephrotoxicity and oxidative stress in rat. Environ Toxicol 2014; 29(10): 1147-1154.
    49. Alcaraz-Contreras Y, Mendoza-Lozano RP, Martínez-Alcaraz ER, et al. Silymarin and dimercaptosuccinic acid ameliorate lead-induced nephrotoxicity and genotoxicity in rats. Hum Exp Toxicol 2016; 35(4): 398-403.
    50. Mohammad SI, Mustafa IA, Abdulqader SZ. Ameliorative effect of the aqueous extract of Zingiber officinale on the cadmium-induced liver and kidney injury in female rats.Jordan J Biol Sci 2013; 6(3): 231-234.
Veterinary Research Forum
Volume 11, Issue 2
Spring 2020
Pages 143-152

  • Receive Date 12 April 2018
  • Revise Date 02 February 2019
  • Accept Date 04 February 2019

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