Skip to main content

Advertisement

Log in

Acute and sub-chronic toxicological evaluation of Averrhoa carambola leaves in Sprague Dawley rats

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

Abstract

Averrhoa carambola is a species of tree native to tropical Southeast Asia. It possesses antioxidant and anti-hyperlipidemia effects and has traditionally been used to treat a variety of ailments. However, the presence of oxalic acid in its fruits might restrict its consumption by individuals suffering from kidney disease, and caramboxin can cause neurotoxicity. In this study, we evaluated the acute and sub-chronic toxicity of the methanolic extract of A. carambola leaves (MEAC) in male and female rats. In the acute study, female rats were given a single oral dose of 5000 mg/kg of MEAC and closely examined for distinct indications of toxic effects during the first 4 h, periodically for 48 h, and daily thereafter for 14 days. Rats of both sexes were employed in the sub-chronic investigation for the 28-day repeated dose oral toxicity study. Results of the acute study revealed the safety of MEAC up to a dose of 5000 mg/kg where the rats did not show changes or signs of toxicity. In the sub-chronic toxicity study, MEAC (250, 500, and 1000 mg/kg) administration did not affect the body weight, food, and water consumption, motor coordination, behavior, or mental alertness in the treated rats. In addition, no variations in hematological or biochemical markers were found in MEAC-treated rats. In conclusion, these findings pinpoint the safety of MEAC at doses up to 5000 mg/kg. The leaves of A. carambola could be safely consumed by people with kidney disease to treat other ailments.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data availability

The authors confirm that the data supporting the findings of this study are available within the article.

References

  • Aladaileh SH, Saghir SAM, Murugesu K, Sadikun A, Ahmad A, Kaur G, Mahmoud AM, Murugaiyah V (2019) Antihyperlipidemic and antioxidant effects of Averrhoa carambola extract in high-fat diet-fed rats. Biomedicines 7(3):72

    Article  CAS  Google Scholar 

  • Araho D, Miyakoshi M, Chou WH, Kambara T, Mizutani K, Ikeda T (2005) A new flavone C-glycoside from the leaves of Averrhoa carambola. Natural Medicines 59:113–116

    CAS  Google Scholar 

  • Bancroft JD, Gamble M (2008) Theory and practice of histological techniques. Elsevier Health Sciences, Amsterdam

    Google Scholar 

  • Cabrini DA, Moresco HH, Imazu P, da Silva CD, Pietrovski EF, Mendes DA, da Silveira Prudente A, Pizzolatti MG, Brighente IM, Otuki MF (2011) Analysis of the potential topical anti-inflammatory activity of Averrhoa carambola L. in mice. Evid Based Complement Alternat Med 2011:908059

  • Carolino RO, Beleboni RO, Pizzo AB, Vecchio FD, Garcia-Cairasco N, Moyses-Neto M, Santos WF, Coutinho-Netto J (2005) Convulsant activity and neurochemical alterations induced by a fraction obtained from fruit Averrhoa carambola (Oxalidaceae: Geraniales). Neurochem Int 46:523–531

    Article  CAS  Google Scholar 

  • Chang JM, Hwang SJ, Kuo HT, Tsai JC, Guh JY, Chen HC, Tsai JH, Lai YH (2000) Fatal outcome after ingestion of star fruit (Averrhoa carambola) in uremic patients. Am J Kidney Dis 35:189–193

    Article  CAS  Google Scholar 

  • Chen CL, Fang HC, Chou KJ, Wang JS, Chung HM (2001) Acute oxalate nephropathy after ingestion of star fruit. Am J Kidney Dis 37:418–422

    Article  CAS  Google Scholar 

  • Christapher PV, Parasuraman S, Asmawi MZ, Murugaiyah V (2017) Acute and subchronic toxicity studies of methanol extract of Polygonum minus leaves in Sprague Dawley rats. Regul Toxicol Pharmacol 86:33–41

    Article  CAS  Google Scholar 

  • El-Ishaq A, Alshawsh MA, Mun KS, Chik Z (2020) Biochemical and toxicological effects of methanolic extract of Asparagus africanus Lam in Sprague-Dawley rats. PeerJ 8:e9138

    Article  Google Scholar 

  • Ferreira EB, Fernandes LC, Galende SB, Cortez DAG, Bazotte RB (2008) Hypoglycemic effect of the hydroalcoholic extract of leaves of Averrhoa carambola L. (Oxalidaceae). Rev Bras 18:339–343

    Google Scholar 

  • Goncalves STBSB-AFAMGANCDAGB-ACACRK (2006) Preliminary studies on gastric anti-ulcerogenic effects of Averrhoa carambola in rats. Acta farmac??utica bonaerense : publicaci??n del Colegio de Farmac??uticos de la Provincia de Buenos Aires (Argentina). 25:245–247

  • Harwood M, Danielewska-Nikiel B, Borzelleca JF, Flamm GW, Williams GM, Lines TC (2007) A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic/carcinogenic properties. Food Chem Toxicol 45:2179–2205

    Article  CAS  Google Scholar 

  • Hobbs CA, Swartz C, Maronpot R, Davis J, Recio L, Koyanagi M, Hayashi SM (2015) Genotoxicity evaluation of the flavonoid, myricitrin, and its aglycone, myricetin. Food Chem Toxicol 83:283–292

    Article  CAS  Google Scholar 

  • Hor SY, Ahmad M, Farsi E, Yam MF, Hashim MA, Lim CP, Sadikun A, Asmawi MZ (2012) Safety assessment of methanol extract of red dragon fruit (Hylocereus polyrhizus): acute and subchronic toxicity studies. Regul Toxicol Pharmacol 63:106–114

    Article  Google Scholar 

  • Krishnaiah D, Bono A, Sarbatly R, Anisuzzaman SM (2015) Antioxidant activity and total phenolic content of an isolated Morinda citrifolia L. methanolic extract from Poly-ethersulphone (PES) membrane separator. J King Saud Univ - Eng Sci 27:63–67

    Google Scholar 

  • Luan F, Peng L, Lei Z, Jia X, Zou J, Yang Y, He X, Zeng N (2021) Traditional uses, phytochemical constituents and pharmacological properties of Averrhoa carambola L.: a review. Front Pharmacol 12:699899

  • Mahmoud AM (2012) Influence of rutin on biochemical alterations in hyperammonemia in rats. Exp Toxicol Pathol 64:783–789

    Article  CAS  Google Scholar 

  • Mia MMRMSBKBBRMA (1970) Phytochemical and Biological Studies of Averrhoa carambola. Dhaka Univ. J. Pharm Sci Dhaka Univ J Pharm Sci 6:125–128

  • Ming Y, Zulkawi NB, Kotak V, Choudhary YK (2013): Acute and sub-acute oral toxicity of polygonum minus aqueous extract (BIOTROPICS ® PM101) IN WISTAR RATS

  • Mohamed Rashid A, Lu K, Yip YM, Zhang D (2016) Averrhoa carambola L. peel extract suppresses adipocyte differentiation in 3T3-L1 cells. Food Funct 7:881–892

    Article  CAS  Google Scholar 

  • Moresco HHQGSPMGBIMC (2012) Chemical constituents and evaluation of the toxic and antioxidant activities of Averrhoa carambola leaves. Rev Bras 22:319–324

    CAS  Google Scholar 

  • Neto MM, da Costa JA, Garcia-Cairasco N, Netto JC, Nakagawa B, Dantas M (2003) Intoxication by star fruit (Averrhoa carambola) in 32 uraemic patients: treatment and outcome. Nephrol Dial Transplant 18:120–125

    Article  Google Scholar 

  • OECD (2008a) Test No. 425: Acute oral toxicity: up-and-down procedure, OECD Guidelines for the Testing of Chemicals, Section 4, OECD Publishing, Paris

  • OECD (2008b) Test no. 407: repeated dose 28-day oral toxicity study in rodents, OECD Guidelines for the Testing of Chemicals, Section 4, OECD Publishing, Paris

  • Pang D, You L, Zhou L, Li T, Zheng B, Liu RH (2017) Averrhoa carambola free phenolic extract ameliorates nonalcoholic hepatic steatosis by modulating mircoRNA-34a, mircoRNA-33 and AMPK pathways in leptin receptor-deficient db/db mice. Food Funct 8:4496–4507

    Article  CAS  Google Scholar 

  • Petchi RR, Vijaya C, Parasuraman S (2014) Antidiabetic activity of polyherbal formulation in streptozotocin - nicotinamide induced diabetic wistar rats. J Tradit Complement Med 4:108–117

    Article  Google Scholar 

  • Ramachandran S, Vamsikrishna M, Gowthami KV, Heera B, Dhanaraju MD (2011) Assessment of cytotoxic activity of Agave cantula using brine shrimp (Artemia salina) lethality bioassay. Asian J Sci Res 4:90–94

    Article  CAS  Google Scholar 

  • Rhiouani H, El-Hilaly J, Israili ZH, Lyoussi B (2008) Acute and sub-chronic toxicity of an aqueous extract of the leaves of Herniaria glabra in rodents. J Ethnopharmacol 118:378–386

    Article  CAS  Google Scholar 

  • Ross JA, Kasum CM (2002) Dietary flavonoids: bioavailability, metabolic effects, and safety. Annu Rev Nutr 22:19–34

    Article  CAS  Google Scholar 

  • Saghir SAM, Sadikun A, Khaw K-Y, Murugaiyah V (2013) Star fruit (Averrhoa carambola L.): From traditional uses to pharmacological activities. Bol Latinoam Caribe Plant Med Aromat 12:209–219

    CAS  Google Scholar 

  • Saghir SA, Sadikun A, Al-Suede FS, Majid AM, Murugaiyah V (2016) Antihyperlipidemic, antioxidant and cytotoxic activities of methanolic and aqueous extracts of different parts of star fruit. Curr Pharm Biotechnol 17:915–925

    Article  CAS  Google Scholar 

  • Stumpf MSABGRM (2020) Acute kidney injury with neurological features: beware of the star fruit and its caramboxin. Indian J Nephrol 30:42–46

    Article  Google Scholar 

  • Teff KL, Kim SF (2011) Atypical antipsychotics and the neural regulation of food intake and peripheral metabolism. Physiol Behav 104:590–598

    Article  CAS  Google Scholar 

  • Tsai MH, Chang WN, Lui CC, Chung KJ, Hsu KT, Huang CR, Lu CH, Chuang YC (2005) Status epilepticus induced by star fruit intoxication in patients with chronic renal disease. Seizure 14:521–525

    Article  Google Scholar 

  • Wei S-D, Chen H, Yan T, Lin Y-M, Zhou H-C (2014) Identification of antioxidant components and fatty acid profiles of the leaves and fruits from Averrhoa carambola. LWT Food Sci Technol 55:278–285

    Article  CAS  Google Scholar 

  • WHO (2009) Global health risks : mortality and burden of disease attributable to selected major risks. World Health Organization, Geneva

  • Yasawardene P, Jayarajah U, De Zoysa I, Seneviratne SL (2020) Mechanisms of star fruit (Averrhoa carambola) toxicity: a mini-review. Toxicon 187:198–202

    Article  CAS  Google Scholar 

  • Zhou Y, Yang H, Li Y, Lynch B, Jia X (2015) Broccoli seed extract: genotoxicity and subchronic toxicity studies. Regul Toxicol Pharmacol 73:442–451

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported by Universiti Sains Malaysia (No. 203/PFarmasi/6711190).

Author information

Authors and Affiliations

Authors

Contributions

Sultan A. M. Saghir performed the experiment and analyzed the data. Amirin Sadikun and Vikneswaran Murugaiyah conceived and designed the experiments, contributed materials, and approved the final draft. Mahfoudh A. M. Abdulghani prepared the draft of the manuscript, and tables. Reem S. Alruhaimi, Ahmad F. Ahmeda, Naif A Al-Gabri, and Saleh A. M. A. Alomaisi analyzed the data and prepared the draft of the manuscript. Ayman M. Mahmoud analyzed the data, prepared figures, and tables, and wrote and revised the manuscript.

Corresponding author

Correspondence to Ayman M. Mahmoud.

Ethics declarations

Ethical approval

All of the tests were carried out in compliance with institutional animal experiment rules, and the Animal Ethics Committee at USM (Approval number: USM/Animal Ethics Approval/2014/(92)(573)).

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Responsible editor: Lotfi Aleya

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

Saghir, S.A.M., Abdulghani, M.A.M., Alruhaimi, R.S. et al. Acute and sub-chronic toxicological evaluation of Averrhoa carambola leaves in Sprague Dawley rats. Environ Sci Pollut Res 29, 90058–90069 (2022). https://doi.org/10.1007/s11356-022-22019-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11356-022-22019-7

Keywords

Navigation