Biochanin A Has Protective and Therapeutic Effects against Li2CO3-induced Nephrotoxicity in Rats Model
Abstract
BACKGROUND: Long-term usage of lithium carbonate (Li2CO3) as treatment of bipolar disorder might cause nephrotoxicity. Li2CO3-induced nephrotoxicity usually treated by renal dialysis, which is quite expensive. Usage of natural products that possess anti-inflammatory and antioxidant properties as biochanin A (BCA) may be useful against Li2CO3 nephrotoxicity. Therefore, this study was conducted to evaluate Li2CO3 nephrotoxic effects and BCA therapeutic and protective effects against it.
METHODS: Twenty-eight rats divided into 4 groups: negative control (NC), Li2CO3, Li2CO3 + BCA therapeutic, and BCA + Li2CO3 protective group. Complete blood picture, serum kidney function tests (urea, creatinine, and cystatin C) and kidney tissue homogenate oxidative stress index as malonaldehyde (MDA), superoxide dismutase (SOD), glutathione S-transferase (GST) and catalase (CAT) were measured using enzyme linked immunosorbent assay (ELISA) methods. While, kidney histopathological changes were evaluated under light microscope.
RESULTS: Li2CO3 administration elicited significant changes in hematological parameters as hypochromic anemia, decreased platelets and leukocytosis. Serum urea, creatinine and cystatin C were elevated. Renal homogenate analysis revealed significant elevation of MDA and decline in GST, CAT, SOD levels. Kidney histopathology analysis revealed hemorrhage between renal tubules, glomerular capillaries congestion, Bowman’s space dilatation, structural alterations in renal tubules cells include loss of brush border, deeply stained nuclei and elevated in size and number of cytoplasmic vacuoles. Therapeutic and protective groups of BCA showed amelioration of hematological alteration, kidney functions, oxidative stress markers and restoration of kidney tissues.
CONCLUSION: BCA has both protective and therapeutic effects against Li2CO3-induced nephrotoxicity possibly through the reduction of oxidative stress.
KEYWORDS: biochanin A, hematological changes, kidney, lithium carbonate salt, oxidative stress, protective effects, therapeutic effects
Full Text:
PDFReferences
da Rosa MI, Simon C, Grande AJ, Barichello T, Oses JP, Quevedo J. Serum S100B in manic bipolar disorder patients: Systematic review and meta-analysis. J Affect Disord 2016; 206: 210-5, CrossRef.
Ponzer K, Millischer V, Schalling M, Gissler M, Lavebratt C, Backlund L. Lithium and risk of cardiovascular disease, dementia and venous thromboembolism. Bipolar Disord. 2023; 25(5): 391-401, CrossRef.
Ferensztajn-Rochowiak E, Rybakowski JK. Long-term lithium therapy: Side effects and interactions. Pharmaceuticals. 2023; 16(1): 74, CrossRef.
Grünfeld JP, Rossier BC. Lithium nephrotoxicity revisited. Nat Rev Nephrol. 2009; 5(5): 270-6, CrossRef.
Zheng P, Lin Y, Wang F, Luo R, Zhang T, Hu S, et al. 4-PBA improves lithium-induced nephrogenic diabetes insipidus by attenuating ER stress. Am J Physiol Renal Physiol. 2016; 311(4): F763-76, CrossRef.
Oktem F, Ozguner F, Sulak O, Olgar S, Akturk O, Yilmaz HR, et al. Lithium-induced renal toxicity in rats: protection by a novel antioxidant caffeic acid phenethyl ester. Mol Cell Biochem. 2005; 277(1-2): 109-15, CrossRef.
Tas HI, Sancak EB. Protective effect of metformin on lithium-induced nephrogenic diabetes insipidus: An experimental study in rats. Adv Clin Exp Med. 2021; 30(11): 1185-93, CrossRef.
Saad AB, Rjeibi I, Ncib S, Zouari N, Zourgui L. Ameliorative effect of cactus (Opuntia ficus indica) extract on lithium-induced nephrocardiotoxicity: A biochemical and histopathological study. Biomed Res Int. 2017: 2017: 8215392, CrossRef.
Ahmad M, Elnakady Y, Farooq M, Wadaan M. Lithium induced toxicity in rats: Blood serum chemistry, antioxidative enzymes in red blood cells and histopathological studies. Biol Pharm Bull. 2011; 34(2): 272-7, CrossRef.
Lopez JC, Perez X, Labad J, Esteve F, Manez R, Javierre C. Higher requirements of dialysis in severe lithium intoxication. Hemodial Int. 2012; 16(3): 407-13, CrossRef.
Alsady M, Baumgarten R, Deen PM, de Groot T. Lithium in the kidney: Friend and foe? J Am Soc Nephrol. 2016; 27(6): 1587-95, CrossRef.
Erbaş E, Üstündağ H, Öztürk E, Parlak SN, Atcalı T. Astaxanthin treatment reduces kidney damage and facilitates antioxidant recovery in lithium-intoxicated rats. Toxicon. 2024; 241: 107664, CrossRef.
Rusmana D, Wahyudianingsih R, Elisabeth M, Balqis B, Maesaroh M, Widowati W. Antioxidant activity of Phyllanthus niruri extract, rutin and quercetin. Indones Biomed J. 2017; 9(2): 84-90, CrossRef.
Felix FB, Vago JP, Beltrami VA, Araújo JMD, Grespan R, Teixeira MM, et al. Biochanin A as a modulator of the inflammatory response: An updated overview and therapeutic potential. Pharmacol Res. 2022: 180: 106246, CrossRef.
Ram C, Gairola S, Syed AM, Kulhari U, Kundu S, Mugale MN, et al. Biochanin A alleviates unilateral ureteral obstruction-induced renal interstitial fibrosis and inflammation by inhibiting the TGF-β1/Smad2/3 and NF-kB/NLRP3 signaling axis in mice. Life Sci. 2022: 298: 120527, CrossRef.
Amri J, Alaee M, Babaei R, Salemi Z, Meshkani R, Ghazavi A, et al. Biochanin-A has antidiabetic, antihyperlipidemic, antioxidant, and protective effects on diabetic nephropathy via suppression of TGF-β1 and PAR-2 genes expression in kidney tissues of STZ-induced diabetic rats. Biotechnol Appl Biochem. 2022; 69(5): 2112-21, CrossRef.
Sharma SD, Iqbal M. Lithium induced toxicity in rats: A hematological, biochemical and histopathological study. Biol Pharm Bull. 2005; 28(5): 834-7, CrossRef.
Aboukamar WA, Elhenawy AA, Elmehankar MS, Elzoheiry MA, El-Gamal R, Elabbasy LM, et al. Activity of isoflavone biochanin A in chronic experimental toxoplasmosis: impact on inflammation. Parasitol Res. 2022; 121(8): 2405-14, CrossRef.
Al-Attar AM, Al-Rethea HA. Chemoprotective effect of omega-3 fatty acids on thioacetamide induced hepatic fibrosis in male rats. Saudi J Biol Sci. 2017; 24(4): 956-65, CrossRef.
Adams WK, Levesque DL, Cocker PJ, Kaur S, Bodnar TS, Young AH, Winstanley CA. Decreased motor impulsivity following chronic lithium treatment in male rats is associated with reduced levels of pro-inflammatory cytokines in the orbitofrontal cortex. Brain Behav Immun. 2020; 89: 339-49, CrossRef.
Habib MZ, Ebeid MA, El Faramawy Y, Saad SST, El Magdoub HM, Attia AA, et al. Effects of lithium on cytokine neuro-inflammatory mediators, Wnt/β-catenin signaling and microglial activation in the hippocampus of chronic mild stress-exposed rats. Toxicol Appl Pharmacol. 2020: 399: 115073, CrossRef.
Ibrahim MY, Alamri ZZ, Juma ASM, Hamood SA, Shareef SH, Abdulla MA, et al. Hepatoprotective effects of biochanin A on thioacetamide-induced liver cirrhosis in experimental rats. Molecules. 2023; 28(22): 7608, CrossRef.
Ram C, Gairola S, Verma S, Mugale MN, Bonam SR, Murty US, et al. Biochanin A ameliorates nephropathy in high-fat diet/streptozotocin-induced diabetic rats: Effects on NF-kB/NLRP3 axis, pyroptosis, and fibrosis. Antioxidants. 2023; 12(5): 1052, CrossRef.
Olayode OA, Daniyan MO, Olayiwola G. Biochemical, hematological and histopathological evaluation of the toxicity potential of the leaf extract of Stachytarpheta cayennensis in rats. J Tradit Complement Med. 2019; 10(6): 544-54, CrossRef.
Malhotra A, Dhawan DK. Zinc improves antioxidative enzymes in red blood cells and hematology in lithium-treated rats. Nutr Res. 2008; 28(1): 43-50, CrossRef.
Jalaludeen AM, Ha WT, Lee R, Kim JH, Do JT, Park C, et al. Biochanin A ameliorates arsenic-induced hepato- and hematotoxicity in rats. Molecules. 2016; 21(1): 69, CrossRef.
Dharnidharka VR, Kwon C, Stevens G. Serum cystatin C is superior to serum creatinine as a marker of kidney function: A meta-analysis. Am J Kidney Dis. 2002; 40(2): 221-6, CrossRef.
Bondok AA, Saleh DM, Erfan OS, Hassan HM. Lithium carbonate-induced nephrotoxicity in albino rats and the possible protective effect of vitamin e: Histological and immunohistochemical study. Egypt J Anat. 2018; 41: 105-18, CrossRef.
Alaee M, Akbari A, Karami H, Salemi Z, Amri J, Panahi M. Antidiabetic and protective effects of Scrophularia striata ethanolic extract on diabetic nephropathy via suppression of RAGE and S100A8 expression in kidney tissues of streptozotocin-induced diabetic rats. J Basic Clin Physiol Pharmacol. 2020; 31(2): 20190186, CrossRef.
Jalaludeen AM, Lee WY, Kim JH, Jeong HY, Ki KS, Kwon EG, et al. Therapeutic efficacy of biochanin A against arsenic-induced renal and cardiac damage in rats. Environ Toxicol Pharmacol. 2015; 39(3): 1221-31, CrossRef.
Tariq M, Morais C, Sobki S, Al Sulaiman M, Al Khader A. Effect of lithium on cyclosporin induced nephrotoxicity in rats. Ren Fail. 2000; 22(5): 545-60, CrossRef.
Dixon RA, Ferreira D. Genistein. Phytochemistry. 2002; 60(3): 205-11, CrossRef.
Shaterpour M, Shaki F, Ghasemi M, Jafari-Sabet M, Ziar A, Ataee R. The protective effect of curcumin against lithium-induced nephrotoxicity in rats. Pharm Biomed Res. 2017; 3(2): 33-8, CrossRef.
Lepkifker E, Sverdlik A, Iancu I, Ziv R, Segev S, Kotler M. Renal insufficiency in long-term lithium treatment. J Clin Psychiatry. 2004; 65(6): 850-6, CrossRef.
Therien AG, Blostein R. Mechanisms of sodium pump regulation. Am J Physiol Cell Physiol. 2000; 279(3): C541-66, CrossRef.
Boton R, Gaviria M, Batlle DC. Prevalence, pathogenesis, and treatment of renal dysfunction associated with chronic lithium therapy. Am J Kidney Dis. 1987; 10(5): 329-45, CrossRef.
Nielsen RE, Kessing LV, Nolen WA, Licht RW. Lithium and renal impairment: A review on a still hot topic. Pharmacopsychiatry. 2018; 51(5): 200-5, CrossRef.
Oliveira JL, Silva Júnior GB, Abreu KL, Rocha Nde A, Franco LF, Araújo SM, et al. Lithium nephrotoxicity. Rev Assoc Med Bras. 2010; 56(5): 600-6, CrossRef.
Suliman FA, Khodeer DM, Ibrahiem A, Mehanna ET, El-Kherbetawy MK, Mohammad HMF, et al. Renoprotective effect of the isoflavonoid biochanin A against cisplatin induced acute kidney injury in mice: Effect on inflammatory burden and p53 apoptosis. Int Immunopharmacol. 2018: 61: 8-19, CrossRef.
DOI: https://doi.org/10.18585/inabj.v16i3.3077
Copyright (c) 2024 The Prodia Education and Research Institute
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Indexed by:
The Prodia Education and Research Institute
