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Ameliorative potential of betaine against arsenite-induced hepatotoxicity and nephrotoxicity

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Abstract

Considering several limitations as well as accompanying side effects of currently available arsenic antidotes, it is essential to conduct research studies to find better therapeutic and prophylactic agents against arsenicosis. The purpose of the present study was to investigate the ameliorative effects of betaine versus arsenite-induced alterations of some biochemical parameters indicative of oxidative stress and infliction of the liver and kidney. Twenty-four adult male rats were divided into four groups: group I or control received normal tap water and a basal diet, group II was administered 100 ppm arsenite in tap water, group III was given betaine (2% of the diet) during exposure to arsenite, and group IV received betaine (2% of the diet) for 30 days. The results of this study showed a significant decline in glutathione, catalase, and superoxide dismutase values as well as increased malondialdehyde in the liver and kidney of arsenite-treated animals compared to the ones in the control group. Likewise, a significant rise of plasma AST, ALT, ALP, and urea, as well as a decline of total protein, could reflect As-induced hepatic and renal injury. Betaine administration in As‐intoxicated mice of group ΙΙΙ significantly enhanced values of hepatic GSH as well as renal catalase amounts relative to group ΙΙ. Betaine administration in group III notably increased SOD and attenuated malondialdehyde values of the liver and kidney to levels that did not significantly differ from those in the control group. Moreover, the use of betaine in group ΙΙΙ notably altered the values of ALT, ALP, total protein, AST, and urea relative to group ΙΙ to the amounts that were comparable to the control group. These findings indicated that betaine administration had been partly successful in restoring As-induced alterations in the oxidative and biochemical marker indices of liver and kidney damage in rats. Therefore, betaine can be regarded as a potential candidate to diminish As-induced toxicity in the liver and kidney, which could be due to its antioxidant nature as well as methyl donor properties.

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References

  • Adil M, Kandhare AD, Visnagri A, Bodhankar SL (2015) Naringin ameliorates sodium arsenite-induced renal and hepatic toxicity in rats: decisive role of KIM-1, Caspase-3, TGF-β, and TNF-α. Ren Fail 37:1396–1407

    Article  CAS  PubMed  Google Scholar 

  • Alirezaei M, Jelodar G, Ghayemi Z (2012a) Antioxidant defense of betaine against oxidative stress induced by ethanol in the rat testes. Int J Pept Res Ther 18:239–247

    Article  CAS  Google Scholar 

  • Alirezaei M, Jelodar G, Ghayemi Z, Mehr MK (2014) Antioxidant and methyl donor effects of betaine versus ethanol-induced oxidative stress in the rat liver. Comp Clin Pathol 23:161–168

    Article  CAS  Google Scholar 

  • Alirezaei M, Niknam P, Jelodar G (2012b) Betaine elevates ovarian antioxidant enzyme activities and demonstrates methyl donor effect in non-pregnant rats. Int J Pept Res Ther 18:281–290

    Article  CAS  Google Scholar 

  • Alirezaei M, Saeb M, Javidnia K, Nazifi S, Saeb S (2011) Hyperhomocysteinemia reduction in ethanol-fed rabbits by oral betaine. Comp Clin Pathol 21:421–427

    Article  Google Scholar 

  • Balarastaghi S, Rezaee R, Hayes AW, Yarmohammadi F, Karimi G (2023) Mechanisms of arsenic exposure-induced hypertension and atherosclerosis: an updated overview. Biol Trace Elem Res 201:98–113

    Article  CAS  PubMed  Google Scholar 

  • Baltaci B, Uygur R, Caglar V, Aktas C, Aydin M, Ozen O (2016) Protective effects of quercetin against arsenic-induced testicular damage in rats. Andrologia 48:1202–1213

    Article  CAS  PubMed  Google Scholar 

  • Barai M, Ahsan N, Paul N, Hossain K, Rashid MA, Kato M, Ohgami N, Akhand AA (2017) Amelioration of arsenic-induced toxic effects in mice by dietary supplementation of Syzygium cumini leaf extract. Nagoya J Med Sci 79:167

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bostrom B, Sweta B, James SJ (2015) Betaine for patients with acute lymphoblastic leukemia intolerant of maintenance chemotherapy due deficiency of S-adenosyl methionine. Blood 126:1296

    Article  Google Scholar 

  • Das B, Rahman MM, Nayak B, Pal A, Chowdhury UK, Mukherjee SC, Saha KC, Pati S, Quamruzzaman Q, Chakraborti D (2009) Groundwater arsenic contamination, its health effects and approach for mitigation in West Bengal, India and Bangladesh. Water Qual Expo Health 1:5–21

    Article  CAS  Google Scholar 

  • Das N, Paul S, Chatterjee D, Banerjee N, Majumder NS, Sarma N, Sau TJ, Basu S, Banerjee S, Majumder P (2012) Arsenic exposure through drinking water increases the risk of liver and cardiovascular diseases in the population of West Bengal, India. BMC Public Health 12:1–9

    Article  Google Scholar 

  • Day CR, Kempson SA (2016) Betaine chemistry, roles, and potential use in liver disease. Biochimica et Biophysica Acta (BBA)-General Subjects 1860:1098–1106

  • Eisler R (1988) Arsenic hazards to fish, wildlife, and invertebrates: a synoptic review (CHR Rep. No. 12). U.S. Department of the Interior, U.S. Fish and Wildlife Service. Washington, D.C. 92

  • Flora S, Mehta A, Gautam P, Jatav P, Pathak U (2007) Essential metal status, prooxidant/antioxidant effects of MiADMSA in male rats: age-related effects. Biol Trace Elem Res 120:235–247

    Article  CAS  PubMed  Google Scholar 

  • Flora SJ (2011) Arsenic-induced oxidative stress and its reversibility. Free Radical Biol Med 51:257–281

    Article  CAS  Google Scholar 

  • Fouad AA, Al-Sultan AI, Yacoubi MT (2011) Coenzyme Q10 counteracts testicular injury induced by sodium arsenite in rats. Eur J Pharmacol 655:91–98

    Article  CAS  PubMed  Google Scholar 

  • Gupta R, Kannan GM, Sharma M, Flora SJ (2005) Therapeutic effects of Moringa oleifera on arsenic-induced toxicity in rats. Environ Toxicol Pharmacol 20:456–464

    Article  CAS  PubMed  Google Scholar 

  • Hagar H, El Medany A, Salam R, El Medany G, Nayal OA (2015) Betaine supplementation mitigates cisplatin-induced nephrotoxicity by abrogation of oxidative/nitrosative stress and suppression of inflammation and apoptosis in rats. Exp Toxicol Pathol 67:133–141

    Article  CAS  PubMed  Google Scholar 

  • Hemmati A, Olapour S, Varzi HN, Khodayar M, Dianat M, Mohammadian B, Yaghooti H (2018) Ellagic acid protects against arsenic trioxide–induced cardiotoxicity in rat. Hum Exp Toxicol 37:412–419

    Article  CAS  PubMed  Google Scholar 

  • Hong Y-S, Song K-H, Chung J-Y (2014) Health effects of chronic arsenic exposure. J Prev Med Public Health 47:245

    Article  PubMed  PubMed Central  Google Scholar 

  • Huang H, Jin WW, Huang M, Ji H, Capen DE, Xia Y, Yuan J, Păunescu TG, Lu HAJ (2020) Gentamicin-induced acute kidney injury in an animal model involves programmed necrosis of the collecting duct. J Am Soc Nephrol 31:2097

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hughes MF, Beck BD, Chen Y, Lewis AS, Thomas DJ (2011) Arsenic exposure and toxicology: a historical perspective. Toxicol Sci 123:305–332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Im Chang S, Jin B, Youn P, Park C, Park J-D, Ryu D-Y (2007) Arsenic-induced toxicity and the protective role of ascorbic acid in mouse testis. Toxicol Appl Pharmacol 218:196–203

    Article  Google Scholar 

  • Kheradmand A, Alirezaei M, Asadian P, RafieiAlavi E, Joorabi S (2009) Antioxidant enzyme activity and MDA level in the rat testis following chronic administration of ghrelin. Andrologia 41:335–340

    Article  CAS  PubMed  Google Scholar 

  • Kheradmand A, Dezfoulian O, Tarrahi MJ (2011) Ghrelin attenuates heat-induced degenerative effects in the rat testis. Regul Pept 167:97–104

    Article  CAS  PubMed  Google Scholar 

  • Kim Y-J, Kim J-M (2015) Arsenic toxicity in male reproduction and development. Dev Reprod 19:167

    Article  PubMed  PubMed Central  Google Scholar 

  • Liu H, Gong M, French BA, Li J, Tillman B, French SW (2014) Mallory-Denk Body (MDB) formation modulates ufmylation expression epigenetically in alcoholic hepatitis (AH) and non-alcoholic steatohepatitis (NASH). Exp Mol Pathol 97:477–483

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McLellan F (2002) Arsenic contamination affects millions in Bangladesh. The Lancet 359:1127

    Article  Google Scholar 

  • Nandi D, Patra R, Swarup D (2006) Oxidative stress indices and plasma biochemical parameters during oral exposure to arsenic in rats. Food Chem Toxicol 44:1579–1584

    Article  CAS  PubMed  Google Scholar 

  • Ognjanović BI, Marković SD, Ðorđević NZ, Trbojević IS, Štajn AŠ, Saičić ZS (2010) Cadmium-induced lipid peroxidation and changes in antioxidant defense system in the rat testes: protective role of coenzyme Q10 and vitamin E. Reprod Toxicol 29:191–197

    Article  PubMed  Google Scholar 

  • Orr SE, Bridges CC (2017) Chronic kidney disease and exposure to nephrotoxic metals. Int J Mol Sci 18:1039

    Article  PubMed  PubMed Central  Google Scholar 

  • Ouyang Y, Wu Q, Li J, Sun S, Sun S (2020) S-adenosylmethionine: a metabolite critical to the regulation of autophagy. Cell Prolif 53:e12891

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rahman I, Kode A, Biswas SK (2006) Assay for quantitative determination of glutathione and glutathione disulfide levels using enzymatic recycling method. Nat Protoc 1:3159–3165

    Article  CAS  PubMed  Google Scholar 

  • Ramanathan K, Balakumar B, Panneerselvam C (2002) Effects of ascorbic acid and a-tocopherol on arsenic-induced oxidative stress. Hum Exp Toxicol 21:675–680

    Article  CAS  PubMed  Google Scholar 

  • Ran S, Liu J, Li S (2020) A systematic review of the various effect of arsenic on glutathione synthesis in vitro and in vivo. BioMed Res Int 2020

  • Reddy PS, Rani GP, Sainath S, Meena R, Supriya C (2011) Protective effects of N-acetylcysteine against arsenic-induced oxidative stress and reprotoxicity in male mice. J Trace Elem Med Biol 25:247–253

    Article  CAS  PubMed  Google Scholar 

  • Sankar P, Gopal Telang A, Kalaivanan R, Karunakaran V, Manikam K, Sarkar SN (2015) Effects of nanoparticle-encapsulated curcumin on arsenic-induced liver toxicity in rats. Environ Toxicol 30:628–637

    Article  ADS  CAS  PubMed  Google Scholar 

  • Sayed S, Ahsan N, Kato M, Ohgami N, Rashid A, Akhand AA (2015) Protective effects of phyllanthus emblica leaf extract on sodium arsenite-mediated adverse effects in mice. Nagoya J Med Sci 77:145

    CAS  PubMed  PubMed Central  Google Scholar 

  • Şehirli Ö, Şener E, Şener G, Çetinel Ş, Erzik C, Yeğen BÇ (2008) Ghrelin improves burn-induced multiple organ injury by depressing neutrophil infiltration and the release of pro-inflammatory cytokines. Peptides 29:1231–1240

    Article  PubMed  Google Scholar 

  • Singh MK, Yadav SS, Yadav RS, Singh US, Shukla Y, Pant KK, Khattri S (2014) Efficacy of crude extract of Emblica officinalis (amla) in arsenic-induced oxidative damage and apoptosis in splenocytes of mice. Toxicol Int 21:8

    Article  PubMed  PubMed Central  Google Scholar 

  • Su Q, He Y, Pan H, Liu H, Mehmood K, Tang Z, Hu L (2023) Toxicity of inorganic arsenic to animals and its treatment strategies. Comp Biochem Physiol Part - C Toxicol 109654

  • Vahter M (1994) Species differences in the metabolism of arsenic compounds. Appl Organomet Chem 8:175–182

    Article  CAS  Google Scholar 

  • Zhang M, Zhang H, Li H, Lai F, Li X, Tang Y, Min T, Wu H (2016) Antioxidant mechanism of betaine without free radical scavenging ability. J Agric Food Chem 64:7921–7930

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Hasan Baghshani.

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The study was financially supported by grant no. 3/44872 by Ferdowsi University of Mashhad, Iran. The authors hereby appreciated the relevant authorities.

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The authors declare no competing interests.

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All procedures involving animals and experiments on those animals were approved by the Animal Welfare Committee at Ferdowsi University in Mashhad (permit no. 1392–27816) and by the national guidelines established by the Iranian Ministry of Science, Research, and Technology and based on the 86/609/EEC European Union Directives.

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al-Hafyan, S., Asoodeh, A., Baghshani, H. et al. Ameliorative potential of betaine against arsenite-induced hepatotoxicity and nephrotoxicity. Comp Clin Pathol 33, 155–162 (2024). https://doi.org/10.1007/s00580-023-03535-5

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