Andrographis paniculata mitigates first-line anti-tubercular drugs-induced nephrotoxicity in Wistar rats

Abstract

Context

Anti-tubercular drugs (ATDs) mediated adverse drug reactions are major concerns for clinicians to treat tuberculosis infection. This study aimed to investigate Andrographis paniculata extract-based phytotherapy to combat the nephrotoxic effects caused by ATDs therapy.

Methods

Reno-protective effect of A. paniculata extract in ATDs-induced rats was evaluated through LPO, GSH, CAT, SOD, GST, urea, creatinine, uric acid, and histopathological studies. Standardization of the extract was performed using RP-HPLC and FTIR analysis. Whereas, the effect of A. paniculata extract on ATDs induced genetic perturbation was analyzed using micronucleus assay. Moreover, the expression level of the xenometabolic gene was investigated using RT-PCR to explore the therapeutic mechanism.

Results

The nephrotoxic effect of ATDs was indicated by elevated levels of LPO and renal function markers along with the reduced activity of renal antioxidants. An up-regulated expression profile of NAT gene and histological alterations were observed in renal tissue however, micronucleated PCEs were observed in bone marrow cells. Concomitant treatment with A. paniculata extract revealed a noticeable amelioration of elevated oxidative stress markers, gene expression levels, genotoxic perturbation, and histological alterations in a dose-dependent manner.

Conclusion

Hence, the present study using A. paniculata leaf extract confirmed to play effective phytotherapy against ATDs induced renal toxicity.

Keywords:

• Anti-tubercular drugs
• nephrotoxicity
• Andrographis paniculata
• FTIR
• oxidative stress
• gene expression study

Acknowledgements

We acknowledge the Department of Zoology, Panjab University, Chandigarh, India for providing a conducive environment for this experimental work. We also acknowledge Oniosome Healthcare Pvt. Ltd., Mohali, India, Department of Anthropology and Department of Chemistry, Panjab University, Chandigarh, India for providing HPLC, q-PCR, and FTIR facility, respectively.

Disclosure statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Ethical approval

This study has been approved by the Institutional Animal Ethics Committee, Central Animal House of Panjab University, Chandigarh with ethical clearance reference number PU/45/99/CPCSEA/IAEC/2017/35 for experimenting.

Author contributions

VS designed the experiments, wrote the proposal, participate in data collection, analyzed and drafted the manuscript. VLS supervised and revised the manuscript throughout the process. RS revised the manuscript. All authors read and approved the manuscript and have equal contribution in revision till the final version of the manuscript. The authors declare that all data were generated in-house and that no paper mill was used.

Additional information

Funding

This research work was supported by the University Grant Commission, Delhi, India under Major Research Project grant (F.43-569/2014) and grant of Centre for Advanced Studies (F.4-28/2015/CAS-II/SAP-II).