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l-Carnitine and vitamin E ameliorate cardiotoxicity induced by tilmicosin in rats

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Abstract

The present study aimed to investigate the possible mitigating effect of l-carnitine (LC) and/or α-tocopherol (Vit. E) administration against tilmicosin (TIL)-induced cardiotoxicity in rats. Fifty-six male albino rats were divided into seven groups according to LC, Vit. E, and/or TIL administration. Control, LC, and Vit. E groups were given saline, 150 mg LC/kg body weight (BW)/day and 100 mg Vit. E/kg BW/day, respectively, orally once daily for 15 days. The TIL group was administered saline orally once daily for 15 days and a single dose of TIL (75 mg/kg BW) subcutaneously (SC) on day 14 from the starting of the experimental period (15 days). The TIL-LC, TIL-Vit. E, and TIL-LC-Vit. E groups received 150 mg LC/kg BW/day, 100 mg Vit. E/kg BW/day, and 150 mg LC/kg BW pulse 100 mg Vit. E/kg BW, respectively, orally once daily for 15 days with TIL as described above. The results revealed that the administration of TIL significantly (P ≤ 0.05) raised serum activities of heart injury indicators, lactate dehydrogenase (LDH), creatine kinase (CK), and CK-MB with substantial increase (P ≤ 0.05) in the cardiac contents of malondialdehyde (MDA) and decreased in antioxidants. The pathological changes appeared in the form of necrotic muscle fibers and massive inflammatory cellular infiltrations in the cardiac muscle and increased the caspase-3 immunohistochemical expression in the heart tissues as well. These changes were ameliorated by LC and/or Vit. E administration. In conclusion, supplementation of LC and/or Vit. E ameliorated the cardiotoxicity of the TIL SC injection in the rat.

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References

  • Abdeen A, Abdelkader A, Abdo M, Wareth G, Aboubakr M, Aleya L, Abdel-Daim M (2019a) Protective effect of cinnamon against acetaminophen-mediated cellular damage and apoptosis in renal tissue. Environ Sci Pollut Res 26:240–249

    Article  CAS  Google Scholar 

  • Abdeen A, Abou-Zaid OA, Abdel-Maksoud HA, Aboubakr M, Abdelkader A, Abdelnaby A, Abo-Ahmed AI, El-Mleeh A, Mostafa O, Abdel-Daim M, Aleya L (2019b) Cadmium overload modulates piroxicam-regulated oxidative damage and apoptotic pathways. Environ Sci Pollut Res 26:25167–25177

    Article  CAS  Google Scholar 

  • Abdeen A, Aboubakr M, Elgazzar D, Abdo M, Abdelkader A, Ibrahim S, Elkomy A (2019c) Rosuvastatin attenuates piroxicam-mediated gastric ulceration and hepato-renal toxicity in rats. Biomed Pharmacother 110:895–905

    Article  CAS  Google Scholar 

  • Abdel-Daim M, Eltaysh R, Hassan A, Mousa S (2018) Lycopene attenuates tulathromycin and diclofenac sodium-induced cardiotoxicity in mice. Int J Mol Sci 19(2):344

    Article  CAS  Google Scholar 

  • Abd-Elrazek AM, Ahmed-Farid OAH (2018) Protective effect of L-carnitine and L-arginine against busulfan-induced oligospermia in adult rat. Andrologia 50(1):e12806

    Article  CAS  Google Scholar 

  • Abou Elazab MF, Gomaa GM, Abdo W (2014) Protective effect of S-MethylCysteine against tilmicosin-induced cardiotoxicity in rats. Pak Vet J 34:337–340

    Google Scholar 

  • Aboubakr M, Ibrahim SS, Said AM, Elgendey F, Anis A (2019) Neuroprotective effects of clove oil in acrylamide induced neurotoxicity in rats. Pak Vet J 39(1):111–115

    Article  CAS  Google Scholar 

  • Adiguzel C, Kalender Y (2019) Bendiocarb-induced nephrotoxicity in rats and the protective role of vitamins C and E. Environ Sci Pollut Res 27:6449–6458. https://doi.org/10.1007/s11356-019-07260-x

    Article  CAS  Google Scholar 

  • Aebi H (1984) Catalase in Vitro. Methods Enzimol 105:121–126 BITTENCOURT-OLIVEIRA, MC

    Article  CAS  Google Scholar 

  • Al-Eisa RA, Al-Salmi FA, Hamza RZ, El-Shenawy NS (2018) Role of L-carnitine in protection against the cardiac oxidative stress induced by aspartame in Wistar albino rats. PLoS One 13(11):e0204913

    Article  CAS  Google Scholar 

  • Al-Majed AA (2007) Carnitine deficiency provokes cisplatin-induced hepatotoxicity in rats. Basic Clin Pharmacol Toxicol 100(1503):145

    Article  CAS  Google Scholar 

  • Al-Majed AA, Sayed-Ahmed MM, Al-Yahya AA, Aleisa AM, Al-Rejaie SS, Al-Shabanah OA (2006) Propionyl-L-carnitine prevents the progression of cisplatin-induced cardiomyopathy in a carnitine-depleted rat model. Pharmacol Res 53(3):278–286

    Article  CAS  Google Scholar 

  • Al-Rasheed NM, Al-Rasheed NM, AL-Rabeeah DA, AL-Barrak HS, AL-Salman SA, Ibrahim SA, AL-Hassab SA, Al-Amin MA, Hasan IH, Al-Ajmi HN, AL-Shammari TK (2018) Possible protective mechanisms exerted by metformin or metformin and vitamin E in isoproterenol-induced cardiac injury. J Cell Biochem 119(5):3903–3912

    Article  CAS  Google Scholar 

  • Awad A, Khalil SR, Hendam BM, Abd El-Aziz RM, Metwally MM, Imam TS (2020) Protective potency of Astragalus polysaccharides against tilmicosin- induced cardiac injury via targeting oxidative stress and cell apoptosis-encoding pathways in rat. Environ Sci Pollut Res. https://doi.org/10.1007/s11356-020-08565-y

  • Aziz M, Abd El Fattah MA, Ahmed KA, Moawad H (2019) Protective effects of olmesartan and L-carnitine on doxorubicin induced cardiotoxicity in rats. Can J Physiol Pharmacol 98:183–193. https://doi.org/10.1139/cjpp-2019-0299

    Article  CAS  Google Scholar 

  • Bancroft JD, Gamble M (2007) Theory and practice of histological techniques (p. 800). Churchill Livingstone, Edinburgh

    Google Scholar 

  • Buhl SN, Jackson KY (1978) Optimal conditions and comparison of lactate dehydrogenase catalysis of the lactate-to-pyruvate and pyruvate-to-lactate reactions in human serum at 25, 30, and 37 degrees C. Clin Chem 24(5):828–831

    Article  CAS  Google Scholar 

  • Castrogiovanni P, Trovato FM, Szychlinska MA, Loreto C, Giunta S, Scuderi S, Passanisi R, Fidone F, Fagone P, Imbesi R, Nicoletti F, Castorina R (2016) Effects of synthetic anti-inflammatory sterol in CB3V-induced myocarditis: a morphological study on heart muscle tissue. J Funct Morphol Kinesiol 1(1):69–89

    Article  Google Scholar 

  • Catalgol B, Ozer NK (2012) Protective effects of vitamin E against hypercholesterolemia-induced age-related diseases. Genes Nutr 7(1):91–98

    Article  CAS  Google Scholar 

  • Cetinkaya A, Bulbuloglu E, Kantarceken B, Ciralik H, Kurutas EB, Buyukbese MA, Gumusalan Y (2006) Effects of L-carnitine on oxidant/antioxidant status in acetic acid-induced colitis. Dig Dis Sci 51(3):488–494

    Article  CAS  Google Scholar 

  • Elazab MFA, Gomaa GM, Abdo W (2014) Protective effect of S-methyl cysteine against tilmicosin-induced cardiotoxicity in rats. Pak Vet J 34(3):337–340

    Google Scholar 

  • El-Hack MEA, Mahrose K, Arif M, Chaudhry MT, Saadeldin IM, Saeed M, Soomro RN, Abbasi IHR, Rehman ZU (2017) Alleviating the environmental heat burden on laying hens by feeding on diets enriched with certain antioxidants (vitamin E and selenium) individually or combined. Environ Sci Pollut Res 24(11):10708–10717

    Article  CAS  Google Scholar 

  • Elsayed, M., Elkomy, A., Aboubakr, M., & Morad, M. (2014). Tissue residues, hematological and biochemical effects of tilmicosin in broiler chicken. Veterinary Medicine International, 2014

  • El-Shitany, N. A., & El-Desoky, K. (2016). Protective effects of carvedilol and vitamin C against azithromycin-induced cardiotoxicity in rats via decreasing ROS, IL1-β, and TNF-α production and inhibiting NF-κB and caspase-3 expression. Oxidative medicine and cellular longevity, 2016

  • Er A, Ulutas E, Altan F, Cetin G, Bulbul A, Elmas M, Yazar E (2011) Tulathromycin disturbs blood oxidative and coagulation status. Afr J Biotechnol 10(6):3243–3247

    CAS  Google Scholar 

  • Er A, Tras B, Cetin G, Dik B (2014) Amiodarone may prevent the Tilmicosin-caused lethal toxicity. Acta Sci Vet 42(1):1–4

    Google Scholar 

  • Fadl SE, El-Habashi N, Gad DM, Elkassas WM, Elbialy ZI, Abdelhady DH, Hegazi SM (2019) Effect of adding Dunaliella algae to fish diet on lead acetate toxicity and gene expression in the liver of Nile tilapia. Toxin Rev:1–17

  • Guo D, Cai Y, Chai D, Liang B, Bai N, Wang R (2010) The cardiotoxicity of macrolides: a systematic review. Die Pharmazie-An Int J Pharmaceut Sci 65(9):631–640

    CAS  Google Scholar 

  • Habig WH, Pabst MJ, Jakoby WB (1974) Glutathione S-transferases the first enzymatic step in mercapturic acid formation. J Biol Chem 249(22):7130–7139

    CAS  Google Scholar 

  • Hamza RZ, Al-Harbi MS, El-Shenawy NS (2017) Ameliorative effect of vitamin E and selenium against oxidative stress induced by sodium azide in liver, kidney, testis and heart of male mice. Biomed Pharmacother 91:602–610

    Article  CAS  Google Scholar 

  • Ibrahim AE, Abdel-Daim MM (2015) Modulating effects of Spirulina platensis against tilmicosin-induced cardiotoxicity in mice. Cell J (Yakhteh) 17(1):137

    Google Scholar 

  • Jia Y, Jing Q, Niu H, Huang B (2017) Ameliorative effect of vitamin E on hepatic oxidative stress and hypoimmunity induced by high-fat diet in turbot (Scophthalmus maximus). Fish Shellfish Immunol 67:634–642

    Article  CAS  Google Scholar 

  • Kart A, Yapar K, Karapehlivan M, Citil M (2007) The possible protective effect of L-carnitine on tilmicosin-induced cardiotoxicity in mice. J Veterinary Med Ser A 54(3):144–146

    Article  CAS  Google Scholar 

  • Khalil SR, Abdel-Motal SM, Abd-Elsalam M, Abd El-Hameed NE, Awad A (2020) Restoring strategy of ethanolic extract of Moringa oleifera leaves against tilmicosin-induced cardiac injury in rats: targeting cell apoptosis-mediated pathways. Gene 730:144272

    Article  CAS  Google Scholar 

  • Krajewska M, Wang HG, Krajewski S, Zapata JM, Shabaik A, Gascoyne R, Reed JC (1997) Immunohistochemical analysis of in vivo patterns of expression of CPP32 (caspase-3), a cell death protease. Cancer Res 57(8):1605–1613

    CAS  Google Scholar 

  • Latimer, K. S. (Ed.). (2011) Duncan and Prasse’s veterinary laboratory medicine: clinical pathology. John Wiley & Sons

  • Madkour FF, Abdel-Daim MM (2013) Hepatoprotective and antioxidant activity of Dunaliella salina in paracetamol-induced acute toxicity in rats. Indian J Pharm Sci 75(6):642–648

    Google Scholar 

  • Neumeier D, Prellwitz W, Würzburg U, Brundobler M, Olbermann M, Just HJ, Knedel M, Lang H (1976) Determination of creatine kinase isoenzyme MB activity in serum using immunological inhibition of creatine kinase M subunit activity. Activity kinetics and diagnostic significance in myocardial infarction. Clin Chim Acta 73(3):445–451

    Article  CAS  Google Scholar 

  • Nishikimi M, Rao NA, Yagi K (1972) The occurrence of superoxide anion in the reaction of reduced phenazine methosulfate and molecular oxygen. Biochem Biophys Res Commun 46(2):849–854

    Article  CAS  Google Scholar 

  • Oda SS, Derbalah AE (2018) Impact of diclofenac sodium on tilmicosin-induced acute cardiotoxicity in rats (tilmicosin and diclofenac cardiotoxicity). Cardiovasc Toxicol 18(1):63–75

    Article  CAS  Google Scholar 

  • Papich MG, Riviere JE (2001) Chloramphenicol and derivatives, macrolides, lincosamides, and miscellaneous antimicrobials. Vet Pharmacol Therapeut:868–897

  • Paterna S, Furitano G, Scaffidi L, Barbarino C, Campisi D, Parisi G, Carreca I (1984) Effects of L-carnitine on adriamycin-induced cardiomyopathy in rabbit. Int J Tissue React 6(1):91–95

    CAS  Google Scholar 

  • Salem R, El-Habashi N, Fadl SE, Sakr OA, Elbialy ZI (2018) Effect of probiotic supplement on aflatoxicosis and gene expression in the liver of broiler chicken. Environ Toxicol Pharmacol 60:118–127

    Article  CAS  Google Scholar 

  • Sezen O, Ertekin MV, Demircan B, Karslıoğlu İ, Erdoğan F, Koçer İ, Calik I, Gepdiremen A (2008) Vitamin E and L-carnitine, separately or in combination, in the prevention of radiation-induced brain and retinal damages. Neurosurg Rev 31(2):205–213

    Article  Google Scholar 

  • Shirpoor A, Salami S, Khadem-Ansari MH, Ilkhanizadeh B, Pakdel FG, Khademvatani K (2009) Cardioprotective effect of vitamin E: rescues of diabetes-induced cardiac malfunction, oxidative stress, and apoptosis in rat. J Diabetes Complicat 23(5):310–316

    Article  Google Scholar 

  • Sirolli V, Rossi C, Di Castelnuovo A, Felaco P, Amoroso L, Zucchelli M, Ciavardelli D, Ilio CD, Sacchetta P, Bernardini S, Arduini A, Bonomini M, Urbani A (2012) Toward personalized hemodialysis by low molecular weight amino-containing compounds: future perspective of patient metabolic fingerprint. Blood Transfus 10(Suppl 2):s78

    Google Scholar 

  • Spodniewska A, Barski D, Giżejewska A (2015) Effect of enrofloxacin and chlorpyrifos on the levels of vitamins A and E in Wistar rats. Environ Toxicol Pharmacol 40(2):587–591

    Article  CAS  Google Scholar 

  • Szasz G, Waldenström J, Gruber W (1979) Creatine kinase in serum: 6. Inhibition by endogenous polyvalent cations, and effect of chelators on the activity and stability of some assay components. Clin Chem 25(3):446–452

    Article  CAS  Google Scholar 

  • Takahashi A, Masuda A, Sun M, Centonze VE, Herman B (2004) Oxidative stress-induced apoptosis is associated with alterations in mitochondrial caspase activity and Bcl-2-dependent alterations in mitochondrial pH (pHm). Brain Res Bull 62(6):497–504

    Article  CAS  Google Scholar 

  • Tousson E, Hafez E, Zaki S, Gad A (2016) The cardioprotective effects of L-carnitine on rat cardiac injury, apoptosis, and oxidative stress caused by amethopterin. Environ Sci Pollut Res 23(20):20600–20608

    Article  CAS  Google Scholar 

  • Traber MG, Atkinson J (2007) Vitamin E, antioxidant and nothing more. Free Radic Biol Med 43(1):4–15

    Article  CAS  Google Scholar 

  • Trinder F M, (1969). (Determination of enzymatic pattern in liver) Hawkes, F. 1973 biochemistry and physiology P. 179–7

  • Uchiyama M, Mihara M (1978) Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem 86(1):271–278

    Article  CAS  Google Scholar 

  • Vacante F, Senesi P, Montesano A, Frigerio A, Luzi L, Terruzzi I (2018) L-Carnitine: an antioxidant remedy for the survival of cardiomyocytes under hyperglycemic condition. J Diabetes Res 2018:1–12

    Article  CAS  Google Scholar 

  • Verma RS, Mehta A, Srivastava N (2007) In vivo chlorpyrifos induced oxidative stress: attenuation by antioxidant vitamins. Pestic Biochem Physiol 88(2):191–196

    Article  CAS  Google Scholar 

  • Xie S, Wang F, Wang Y, Zhu L, Dong Z, Wang X, Li X, Zhou W (2011) Acute toxicity study of tilmicosin-loaded hydrogenated castor oil-solid lipid nanoparticles. Particle Fibre Toxicol 8(1):33

    Article  CAS  Google Scholar 

  • Yapar K, Kart A, Karapchlivan M (2006) Effects of different doses of tilmicosin on some biochemical parameters and antioxidant status in serum and cardiac tissues in mice. Bull-Vet Inst Pulawy 50(4):605

    Google Scholar 

  • Yazar E, Altunok V, Elmas M, Tras B, Bas AL, Ozdemir V (2001) Effect of tilmicosin on cardiac muscle and serum creatine kinases activities and serum total protein level in healthy male Balb/C mice. Rev Med Vet 152(12):881–884

    CAS  Google Scholar 

  • Yazar E, Altunok V, Elmas M, Traş B, Baş AL, Özdemir V (2002) The effect of tilmicosin on cardiac superoxide dismutase and glutathione peroxidase activities. J Veterinary Med Ser B 49(4):209–210

    Article  CAS  Google Scholar 

  • Ye J, Li J, Yu Y, Wei Q, Deng W, Yu L (2010) L-carnitine attenuates oxidant injury in HK-2 cells via ROS-mitochondria pathway. Regul Pept 161(1–3):58–66

    Article  CAS  Google Scholar 

  • Yüncü M, Bükücü N, Bayat N, Sencar L, Tarakcioglu M (2015) The effect of vitamin E and L-carnitine against methotrexate-induced injury in rat testis. Turkish J Med Sci 45(3):517–525

    Article  CAS  Google Scholar 

  • Zhang X, Barile G, Chang S, Hays A, Pachydaki S, Schiff W, Sparrow J (2005) Apoptosis and cell proliferation in proliferative retinal disorders: PCNA, Ki-67, caspase-3, and PARP expression. Curr Eye Res 30(5):395–403

    Article  CAS  Google Scholar 

  • Zhao Y, Zhang W, Jia Q, Feng Z, Guo J, Han X, Liu Y, Shang H, Wang Y, Liu WJ (2019) High dose vitamin E attenuates diabetic nephropathy via alleviation of autophagic stress. Front Physiol 9

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Acknowledgments

We would like to thank Dr. Amr El Kelish, Dep. of Biology, Faculty of Science, Suez Canal University, Egypt, for her valuable support.

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Correspondence to Ehab Yahya Abdelhiee.

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Rats were treated in accordance with the Guidelines for Animal Experimentation of the Ethics Review Committee of the Faculty of Veterinary Medicine, Benha University, Egypt (Approval No. 201912).

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Aboubakr, M., Elsayd, F., Soliman, A. et al. l-Carnitine and vitamin E ameliorate cardiotoxicity induced by tilmicosin in rats. Environ Sci Pollut Res 27, 23026–23034 (2020). https://doi.org/10.1007/s11356-020-08919-6

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