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Amelioration of hepatic function, oxidative stress, and histopathologic damages by Cassia fistula L. fraction in thioacetamide-induced liver toxicity

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Abstract

Cassia fistula L. (Caesalpinioideae) is a highly admirable medicinal plant and is traditionally recommended for the treatment of rheumatism, liver disorders, jaundice, and other inflammatory diseases. This study was designed to investigate the hepatoprotective properties of ethyl acetate fraction from C. fistula leaves in an animal model. Treatment with thioacetamide significantly elevated the level of serum glutamic-oxaloacetic transaminase (1.75-fold), alkaline phosphatase (4.07-fold), and total bilirubin (2.29-fold) as compared to the control. It was found that pretreatment of fraction followed by consecutive 2 days thioacetamide reduced the conversion of thioacetamide carcinogen to its reactive metabolites by phase I enzymes and increased the level of detoxification phase II along with antioxidative enzymes. The histopathological studies revealed the hepatoprotective nature of the fraction in restoring the normal architecture of thioacetamide-intoxicated damaged liver. The fraction showed downregulation in the expression level of p-PI3K, p-Akt, and p-mTOR pointing towards its chemopreventive potential. The HPLC analysis of the fraction had shown the dominance of three phenolic compounds namely, catechin, epicatechin, and chlorogenic acid. The above studies comprising histopathological, immunohistochemical, and hepatic enzymes are strong indicative of the potential protective ability of ethyl acetate fraction phytoconstituents against thioacetamide-induced toxicity.

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Data availability

All the data generated and analyzed are included in this article.

Abbreviations

ROS:

reactive oxygen species

RNS:

reactive nitrogen species

HPLC:

high-performance liquid chromatography

MDA:

malondialdehyde

CYP:

cytochrome P450

TAA:

thioacetamide

p-PI3:

phosphorylated-phosphatidylinositol-3-kinase

p-Akt:

phosphorylated-Akt

p-mTOR:

phosphorylated-mammalian target of rapamycin

GSSG:

oxidized glutathione

GSH:

reduced glutathione

bw:

bodyweight

i.p:

intraperitoneal

CPCSEA:

Committee for the Purpose of Control and Supervision of Experiments on Animals

ANOVA:

analysis of variance

MLR:

multiple linear regression

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Acknowledgments

We would like to acknowledge Dr. (Prof.) Mridu Manjari, Department of Pathology (Sri Guru Ramdas Cancer hospital and University of Health Sciences, Amritsar) for performing histopathological studies and for immunohistochemical studies; Centre for Emerging Life Science for HPLC analysis and Mr. Manjinder Singh (Department of Pharmaceutical Sciences) for animal handling, Guru Nanak Dev University, Amritsar.

Funding

This study receives financial assistance provided by the Indian Council of Medical Research (ICMR) [59/36/2011/BMS/TRM] and the Fund for Improvement of S & T Infrastructure (FIST) programme of Department of Science and Technology (DST) [SR/S9/Z-23/2010/20(C)], New Delhi, India.

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Authors and Affiliations

  1. Genetic Toxicology Laboratory, Department of Botanical and Environmental Sciences, Guru Nanak Dev University, Amritsar, Punjab, 143005, India

    Sandeep Kaur, Dipakshi Sharma & Satwinderjeet Kaur

  2. Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, 143005, India

    Amrit Pal Singh

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  1. Sandeep Kaur
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  2. Dipakshi Sharma
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  4. Satwinderjeet Kaur
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Contributions

Provided guidance, drafted the manuscript and revising it critically, and finalized it with her personal inputs: S.J.K. and A.P.S. Performed the experiments and reviewed the literature: S.K., A.P.S, and D.S. Statistical analysis of the results, interpretation of data: S.K., A.P.S, and D.S. Designed the table, figures, and images: S.K and S.J.K.

Corresponding author

Correspondence to Satwinderjeet Kaur.

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Ethical approval and consent to participate

This study was approved by the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSE), Government of India (226/CPCSEA/2014/06). All animals were humane care according to the criteria outlined in the guidelines of the Institutional Animal Ethics Committee (IAEC) and written informed consent was obtained.

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The authors declare that they have no competing interests.

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Responsible editor: Philippe Garrigues

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Highlights

(1) CaLE fraction of C. fistula inhibited the TAA-induced alterations in the hepatic serum marker enzymes in male Wistar rats.

(2) TAA-induced cytochrome b5 activity was effectively inhibited by the CaLE fraction.

(3) IHC studies showed the potential of CaLE fraction in lowering the elevated expression level of p-PI3K, p-Akt, and p-mTOR in TAA-administrated Wistar rats.

4) HPLC analysis revealed the presence of catechin, epicatechin, and chlorogenic acid in appreciable amounts.

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Kaur, S., Sharma, D., Singh, A.P. et al. Amelioration of hepatic function, oxidative stress, and histopathologic damages by Cassia fistula L. fraction in thioacetamide-induced liver toxicity. Environ Sci Pollut Res 26, 29930–29945 (2019). https://doi.org/10.1007/s11356-019-06158-y

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