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Naringenin protects hepato-renal tissues against antituberculosis drugs induced toxic manifestations by modulating interleukin-6, insulin like growth factor-1, biochemical and ultra-structural integrity

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Abstract

Background

The antituberculosis drugs (ATDs), isoniazid, rifampicin, pyrazinamide and ethambutol prompt extreme hepatic and renal damage during treatment of tuberculosis. The present study aimed to investigate protective potential of naringenin against ATDs induced hepato-renal injury.

Methods

Rats were administered with ATDs (pyrazinamide; 210, ethambutol; 170, isoniazid; 85, rifampicin; 65 mg/kg b.wt) orally for 8 weeks (3 days/week) followed by naringenin at three different doses (10, 20 and 40 mg/kg b.wt) conjointly for 8 weeks (3 days/week alternately to ATDs administration) and silymarin (50 mg/kg b.wt) as positive control.

Results

Exposure to ATDs caused significant increase in interleukin-6 (IL-6), triglycerides, cholesterol, bilirubin whereas depletion in insulin like growth factor-1 (IGF-1), albumin and glucose in serum. Endogenous antioxidant enzymes glutathione reductase (GR), glutathione peroxidase (GPx) and glucose-6-phosphate-dehydrogenase (G-6-PDH) were diminished in liver and kidney tissues with parallel increase in triglycerides, cholesterol, microsomal LPO and aniline hydroxylase (CYP2E1 enzyme). Ultra-structural observations of liver and kidney showed marked deviation in plasma membranes of various cellular and sub-cellular organelles after 8 weeks of exposure to ATDs.

Conclusions

Conjoint treatment of naringenin counteracted ATDs induced toxic manifestations by regulating IL-6, IGF-1, CYP2E1, biochemical and ultra-structural integrity in a dose dependent manner. Naringenin has excellent potential to protect ATDs induced hepato-renal injury by altering oxidative stress, modulation of antioxidant enzymes, serum cytokines and ultra-structural changes.

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Acknowledgements

Chhattisgarh Institute of Medical Sciences (CIMS), Bilaspur generously provided antituberculosis drugs for conducting experiments. Technical support was extended from All India Institute of Medical Sciences (AIIMS), New Delhi for electron microscopy.

Funding

The research work was financially supported by University Grants Commission, New Delhi [(F42-520/2013(SR) dated 23-03-2013] sanctioned to Dr. Monika Bhadauria.

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Authors and Affiliations

  1. Toxicology and Pharmacology Laboratory, Department of Zoology, Guru Ghasidas University, 495009, Bilaspur, CG, India

    Nisha Sahu, Samrat Rakshit & Monika Bhadauria

  2. Laboratory of Natural Products, Department of Rural Technology and Social Development, Guru Ghasidas University, 495009, Bilaspur, CG, India

    Satendra Kumar Nirala

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  1. Nisha Sahu
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  2. Samrat Rakshit
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Correspondence to Monika Bhadauria.

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The authors hold no conflict of interest on any issue from this study.

Ethical approval:

All the experiments were held in accordance with the rules set by the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA) India. All the protocols of present study were approved by institutional animal ethics committee (994/Ere/Go/06/CPCSEA).

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Sahu, N., Rakshit, S., Nirala, S.K. et al. Naringenin protects hepato-renal tissues against antituberculosis drugs induced toxic manifestations by modulating interleukin-6, insulin like growth factor-1, biochemical and ultra-structural integrity. Mol Biol Rep 50, 1019–1031 (2023). https://doi.org/10.1007/s11033-022-07799-y

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