Skip to main content
SpringerLink
Log in

The nephroprotective effects of allicin and ascorbic acid against cisplatin-induced toxicity in rats

  • Research Article
  • Published:
Environmental Science and Pollution Research Aims and scope Submit manuscript

Abstract

Cisplatin (CDDP) may induce nephrotoxicity through oxidative stress, DNA damage, and inflammation. This study was performed to evaluate the antioxidant and anti-inflammatory effects of allicin and ascorbic acid (AA) and investigate the nephroprotective efficacy of their combination against CDDP-induced intoxication. Rats were divided into seven groups: control, allicin (10 mg/kg for 14 days), AA (20 mg/kg for 14 days), CDDP (7 mg/kg as a single dose on the seventh experimental day), CDDP-allicin, CDDP-AA, and CDDP-allicin-AA (at the aforementioned doses). The administration of CDDP induced marked body weight loss and renal damage, manifested by significant increases (p < 0.05) in serum creatinine, urea, and uric acid levels and significant reductions in serum Na, Ca, and phosphorus concentrations, in addition to severe alterations in serum and renal tissue levels of tumor necrosis factor-α in comparison with control rats. Moreover, CDDP-intoxicated rats exhibited significantly (p < 0.05) higher lipid peroxidation, as well as lower levels of reduced glutathione and activities of glutathione peroxidase, superoxide dismutase, and catalase enzymes in the renal tissue, compared with control rats. The administration of allicin or AA significantly reduced (p < 0.05) the CDDP-induced changes in all the aforementioned parameters. Interestingly, allicin achieved comparable nephroprotection to AA in most assessed parameters; however, the restoration of normal serum and renal tissue concentrations of these parameters was more frequent in the CDDP-AA group. In conclusion, both allicin and AA showed significant nephroprotective effects against CDDP intoxication and their combination exhibited better protection than either agent alone. These results are probably mediated by their antioxidant and anti-inflammatory activities.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

AA:

ascorbic acid

CAT:

catalase

CDDP:

cis-diamminedichloroplatinum II

GPx:

glutathione peroxidase

GSH:

reduced glutathione

MDA:

malondialdehyde

NO:

nitric oxide

ROS:

reactive oxygen species

SOD:

superoxide dismutase

TAC:

total antioxidant capacity

TNF-α:

tumor necrosis factor-α

References

  • Abdel-Daim MM, Abdelkhalek NK, Hassan AM (2015) Antagonistic activity of dietary allicin against deltamethrin-induced oxidative damage in freshwater Nile tilapia; Oreochromis niloticus. Ecotoxicol Environ Saf 111:146–152

    CAS  Google Scholar 

  • Abdel-Daim MM, Khalifa HA, Ahmed AA (2017) Allicin ameliorates doxorubicin-induced cardiotoxicity in rats via suppression of oxidative stress, inflammation and apoptosis. Cancer Chemother Pharmacol 80:745–753

    CAS  Google Scholar 

  • Abdel-Daim MM, Ahmed A, Ijaz H, Abushouk AI, Ahmed H, Negida A, Aleya L, Bungau SG (2019) Influence of Spirulina platensis and ascorbic acid on amikacin-induced nephrotoxicity in rabbits. Environ Sci Pollut Res 1–7

  • Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126

    CAS  Google Scholar 

  • Alam R, Fawzi EM, Alkhalf MI, Alansari WS, Aleya L, Abdel-Daim MM (2018) Anti-inflammatory, immunomodulatory, and antioxidant activities of allicin, norfloxacin, or their combination against Pasteurella multocida infection in male New Zealand rabbits. Oxidative Med Cell Longev 2018:1–10

    Google Scholar 

  • Ali BH, Al Moundhri MS, Tag Eldin M, Nemmar A, Tanira MO (2007) The ameliorative effect of cysteine prodrug L-2-oxothiazolidine-4-carboxylic acid on cisplatin-induced nephrotoxicity in rats. Fundam Clin Pharmacol 21:547–553

    CAS  Google Scholar 

  • Antunes LM, Darin JD, Bianchi MD (2000) Protective effects of vitamin C against cisplatin-induced nephrotoxicity and lipid peroxidation in adult rats: a dose-dependent study. Pharmacol Res 41:405–411

    CAS  Google Scholar 

  • Arany I, Safirstein RL (2003) Cisplatin nephrotoxicity. Semin Nephrol 23:460–464

    CAS  Google Scholar 

  • Arunkumar PA, Viswanatha GL, Radheshyam N, Mukund H, Belliyappa MS (2012) Science behind cisplatin-induced nephrotoxicity in humans: a clinical study. Asian Pac J Trop Biomed 2:640–644

    CAS  Google Scholar 

  • Badary OA, Abdel-Maksoud S, Ahmed WA, Owieda GH (2005) Naringenin attenuates cisplatin nephrotoxicity in rats. Life Sci 76:2125–2135

    CAS  Google Scholar 

  • Beutler E, Duron O, Kelly BM (1963) Improved method for the determination of blood glutathione. J Lab Clin Med 61:882–888

    CAS  Google Scholar 

  • Borlinghaus J, Albrecht F, Gruhlke MC, Nwachukwu ID, Slusarenko AJ (2014) Allicin: chemistry and biological properties. Molecules 19:12591–12618

    Google Scholar 

  • Camano S, Lazaro A, Moreno-Gordaliza E, Torres AM, de Lucas C, Humanes B, Lazaro JA, Milagros Gomez-Gomez M, Bosca L, Tejedor A (2010) Cilastatin attenuates cisplatin-induced proximal tubular cell damage. J Pharmacol Exp Ther 334:419–429

    CAS  Google Scholar 

  • Chen W, Qi J, Feng F, Wang MD, Bao G, Wang T, Xiang M, Xie WF (2014) Neuroprotective effect of allicin against traumatic brain injury via Akt/endothelial nitric oxide synthase pathway-mediated anti-inflammatory and anti-oxidative activities. Neurochem Int 68:28–37

    CAS  Google Scholar 

  • Chirino YI, Pedraza-Chaverri J (2009) Role of oxidative and nitrosative stress in cisplatin-induced nephrotoxicity. Exp Toxicol Pathol 61:223–242

    CAS  Google Scholar 

  • Coulombe JJ, Favreau L (1963) A new simple semimicro method for colorimetric determination of urea. Clin Chem 9:102–108

    CAS  Google Scholar 

  • Davis CA, Nick HS, Agarwal A (2001) Manganese superoxide dismutase attenuates cisplatin-induced renal injury: importance of superoxide. J Am Soc Nephrol 12:2683–2690

    CAS  Google Scholar 

  • El Din AM, Sherif RN, El Khyat SM, Salem YG (2018) The potential combined effect of vitamins E and C on fluoride-induced hepatic toxicity in albino rats. Benha Med J 35:326

    Google Scholar 

  • El-Kashef DH, El-Kenawi AE, Suddek GM, Salem HA (2015) Protective effect of allicin against gentamicin-induced nephrotoxicity in rats. Int Immunopharmacol 29:679–686

    CAS  Google Scholar 

  • El-Naga RN (2014) Pre-treatment with cardamonin protects against cisplatin-induced nephrotoxicity in rats: impact on NOX-1, inflammation and apoptosis. Toxicol Appl Pharmacol 274:87–95

    CAS  Google Scholar 

  • Faubel S, Lewis EC, Reznikov L, Ljubanovic D, Hoke TS, Somerset H, Oh DJ, Lu L, Klein CL, Dinarello CA, Edelstein CL (2007) Cisplatin-induced acute renal failure is associated with an increase in the cytokines interleukin (IL)-1beta, IL-18, IL-6, and neutrophil infiltration in the kidney. J Pharmacol Exp Ther 322:8–15

    CAS  Google Scholar 

  • Fouad AA, Al-Sultan AI, Refaie SM, Yacoubi MT (2010) Coenzyme Q10 treatment ameliorates acute cisplatin nephrotoxicity in mice. Toxicology 274:49–56

    CAS  Google Scholar 

  • Frei B, England L, Ames BN (1989) Ascorbate is an outstanding antioxidant in human blood plasma. Proc Natl Acad Sci U S A 86:6377–6381

    CAS  Google Scholar 

  • Gonen A, Harats D, Rabinkov A, Miron T, Mirelman D, Wilchek M, Weiner L, Ulman E, Levkovitz H, Ben-Shushan D (2005) The antiatherogenic effect of allicin: possible mode of action. Pathobiology 72:325–334

    CAS  Google Scholar 

  • Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR (1982) Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem 126:131–138

    CAS  Google Scholar 

  • Howard PA, Meyers DG (1995) Effect of vitamin C on plasma lipids. Ann Pharmacother 29:1129–1136

    CAS  Google Scholar 

  • Kadikoylu G, Bolaman Z, Demir S, Balkaya M, Akalin N, Enli Y (2004) The effects of desferrioxamine on cisplatin-induced lipid peroxidation and the activities of antioxidant enzymes in rat kidneys. Hum Exp Toxicol 23:29–34

    CAS  Google Scholar 

  • Koracevic D, Koracevic G, Djordjevic V, Andrejevic S, Cosic V (2001) Method for the measurement of antioxidant activity in human fluids. J Clin Pathol 54:356–361

    CAS  Google Scholar 

  • Kuhlmann MK, Burkhardt G, Kohler H (1997) Insights into potential cellular mechanisms of cisplatin nephrotoxicity and their clinical application. Nephrol Dial Transplant 12:2478–2480

    CAS  Google Scholar 

  • Larsen K (1972) Creatinine assay in the presence of protein with LKB 8600 Reaction Rate Analyser. Clin Chim Acta Int J Clin Chem 38:475–476

    CAS  Google Scholar 

  • Maldonado PD, Barrera D, Rivero I, Mata R, Medina-Campos ON, Hernandez-Pando R, Pedraza-Chaverri J (2003) Antioxidant S-allylcysteine prevents gentamicin-induced oxidative stress and renal damage. Free Radic Biol Med 35:317–324

    CAS  Google Scholar 

  • Mihara M, Uchiyama M (1978) Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem 86:271–278

    CAS  Google Scholar 

  • Murray MT, Pizzorno JA (1998) Encyclopedia of natural medicine

  • Nasr AY, Saleh HA (2014) Aged garlic extract protects against oxidative stress and renal changes in cisplatin-treated adult male rats. Cancer Cell Int 14:92

    Google Scholar 

  • Naziroglu M, Karaoglu A, Aksoy AO (2004) Selenium and high dose vitamin E administration protects cisplatin-induced oxidative damage to renal, liver and lens tissues in rats. Toxicology 195:221–230

    CAS  Google Scholar 

  • Nishikimi M, Appaji N, Yagi K (1972) The occurrence of superoxide anion in the reaction of reduced phenazine methosulfate and molecular oxygen. Biochem Biophys Res Commun 46:849–854

    CAS  Google Scholar 

  • NRC (1995) Nutrient requirements of laboratory animals: 1995. National Academies Press

  • Oh GS, Kim HJ, Shen A, Lee SB, Khadka D, Pandit A, So HS (2014) Cisplatin-induced kidney dysfunction and perspectives on improving treatment strategies. Electrolyte Blood Press 12:55–65

    CAS  Google Scholar 

  • Osman M, Adnan A, Bakar NS, Alashkham F (2012) Allicin has significant effect on autoimmune anti-islet cell antibodies in type 1 diabetic rats. Pol J Pathol 63:248–254

    CAS  Google Scholar 

  • Padayatty SJ, Levine M (2001) New insights into the physiology and pharmacology of vitamin C. CMAJ 164:353–355

    CAS  Google Scholar 

  • Padayatty SJ, Katz A, Wang Y, Eck P, Kwon O, Lee JH, Chen S, Corpe C, Dutta A, Dutta SK, Levine M (2003) Vitamin C as an antioxidant: evaluation of its role in disease prevention. J Am Coll Nutr 22:18–35

    CAS  Google Scholar 

  • Paglia DE, Valentine WN (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70:158–169

    CAS  Google Scholar 

  • Pedraza-Chaverri J, Yam-Canul P, Chirino YI, Sanchez-Gonzalez DJ, Martinez-Martinez CM, Cruz C, Medina-Campos ON (2008) Protective effects of garlic powder against potassium dichromate-induced oxidative stress and nephrotoxicity. Food Chem Toxicol 46:619–627

    CAS  Google Scholar 

  • Razo-Rodríguez AC, Chirino YI, Sánchez-González DJ, Martínez-Martínez CM, Cruz C, Pedraza-Chaverri J (2008) Garlic powder ameliorates cisplatin-induced nephrotoxicity and oxidative stress. J Med Food 11:582–586

    Google Scholar 

  • Saad SY, Najjar TA, Alashari M (2004) Role of non-selective adenosine receptor blockade and phosphodiesterase inhibition in cisplatin-induced nephrogonadal toxicity in rats. Clin Exp Pharmacol Physiol 31:862–867

    CAS  Google Scholar 

  • Sahu BD, Rentam KK, Putcha UK, Kuncha M, Vegi GM, Sistla R (2011) Carnosic acid attenuates renal injury in an experimental model of rat cisplatin-induced nephrotoxicity. Food Chem Toxicol 49:3090–3097

    CAS  Google Scholar 

  • Schrier RW (2002) Cancer therapy and renal injury. J Clin Invest 110:743–745

    CAS  Google Scholar 

  • Shimeda Y, Hirotani Y, Akimoto Y, Shindou K, Ijiri Y, Nishihori T, Tanaka K (2005) Protective effects of capsaicin against cisplatin-induced nephrotoxicity in rats. Biol Pharm Bull 28:1635–1638

    CAS  Google Scholar 

  • Sindhu G, Nishanthi E, Sharmila R (2015) Nephroprotective effect of vanillic acid against cisplatin induced nephrotoxicity in wistar rats: a biochemical and molecular study. Environ Toxicol Pharmacol 39:392–404

    CAS  Google Scholar 

  • Su Q-S, Tian Y, Zhang J-G, Zhang H (2008) Effects of allicin supplementation on plasma markers of exercise-induced muscle damage, IL-6 and antioxidant capacity. Eur J Appl Physiol 103:275–283

    CAS  Google Scholar 

  • Ugur S, Ulu R, Dogukan A, Gurel A, Yigit IP, Gozel N, Aygen B, Ilhan N (2015) The renoprotective effect of curcumin in cisplatin-induced nephrotoxicity. Ren Fail 37:332–336

    CAS  Google Scholar 

  • Vijayan FP, Rani VK, Vineesh VR, Sudha KS, Michael MM, Padikkala J (2007) Protective effect of Cyclea peltata Lam on cisplatin-induced nephrotoxicity and oxidative damage. J Basic Clin Physiol Pharmacol 18:101–114

    CAS  Google Scholar 

  • Whitehead TP, Bevan EA, Miano L, Leonardi A (1991) Defects in diagnostic kits for determination of urate in serum. Clin Chem 37:879–881

    CAS  Google Scholar 

  • Wu G, Fang YZ, Yang S, Lupton JR, Turner ND (2004) Glutathione metabolism and its implications for health. J Nutr 134:489–492

    CAS  Google Scholar 

Download references

Funding

This work was supported by the Deanship of Scientific Research at King Saud University, Saudi Arabia (Grant No. RGP-018).

Author information

Authors and Affiliations

  1. Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, Egypt

    Mohamed M. Abdel-Daim

  2. Faculty of Medicine, Ain Shams University, Ramsis St, Abbasia, 11566, Cairo, Egypt

    Abdelrahman Ibrahim Abushouk

  3. Chemistry Department, Faculty of Science, Tanta University, Tanta, Egypt

    Thoria Donia

  4. Department of Zoology, Science College, King Saud University, Riyadh, Saudi Arabia

    Saud Alarifi & Saad Alkahtani

  5. Chrono-Environnement Laboratory, UMR CNRS 6249, Bourgogne Franche-Comté University, F-25030, Besançon Cedex, France

    Lotfi Aleya

  6. Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, Oradea, Romania

    Simona G. Bungau

Authors
  1. Mohamed M. Abdel-Daim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Abdelrahman Ibrahim Abushouk
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Thoria Donia
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Saud Alarifi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Saad Alkahtani
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lotfi Aleya
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Simona G. Bungau
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Mohamed M. Abdel-Daim or Abdelrahman Ibrahim Abushouk.

Ethics declarations

The ethical committee at the Faculty of Veterinary Medicine, Suez Canal University (Ismailia, Egypt), granted the study approval (protocol no. 201613).

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

Responsible editor: Philippe Garrigues

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Abdel-Daim, M.M., Abushouk, A.I., Donia, T. et al. The nephroprotective effects of allicin and ascorbic acid against cisplatin-induced toxicity in rats. Environ Sci Pollut Res 26, 13502–13509 (2019). https://doi.org/10.1007/s11356-019-04780-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11356-019-04780-4

Keywords

Search

Navigation