Commelina benghalensis attenuates cyclophosphamide induced hepatotoxicity by preserving hepatic mitochondrial activity through upregulating pro-mitochondrial proteins

Author:

Allakonda Lingesh1,Potnuri Ajay Godwin2,Ranjan Rakshit3,Danaboina Gnana Bhaskar1,Kurra Subramanyam1,Kumar Sudheer4

Affiliation:

1. Regional Ayurveda Research Institute for Drug Development

2. All India Institute of Medical Sciences

3. Natural Remedies (India)

4. Biogenic products Pvt Ltd

Abstract

Abstract

Background Anticancer therapy is largely impeded by its non-specificity and toxicity. They induce cell death by triggering oxidative stress. Cyclophosphamide (CP) is used as antineoplastic agent against solid tumours, lymphomas and leukaemias. Metabolites of CP will potentially damage the glutathione reserves and thereby induces cell death. Strategies that can attenuate this off-target effect of CP could be helpful in successful treatment of cancers with fewer side effects. Commelina benghalensis (Linn) belongs to apocynaceae family and is widely used in oriental traditional medicine. Despite of its medicinal value, its potential against drug induced hepatotoxicity is unknown. The present study evaluates the hepatoprotective effect of hydroethanolic extract of Commelina benghalensis (HECB) in rat model of CP induced hepatotoxicity. Methods Chemical characterization of HECB was carried out followed by DPPH assay. Liver weight, serum hepatic enzyme activity and hepatic antioxidant reserves were estimated after treatments at 50 and 100 mg/kg for 8 weeks. Inflammatory markers such as IL-6 and TNFα were analysed in the tissue lysates. Mitochondrial integrity was performed by analysing Complex I activity followed by estimating the NRF2 and Mitochondrial Transcriptional Factor A (TFAM) levels. Histopathological analysis of liver was carried out and phenobarbitone induced sleeping time was performed to confirm the hepatoprotective effect. Results Flavonoids and phenolic compounds were found at higher concentrations of 50 and 100 µg/ml with a significant free radical scavenging activity as displayed by DPPH assay. Administration of CP has resulted in increased liver weight, elevated serum hepatic enzyme activity along with Inflammatory markers, decreased hepatic antioxidant reserves, profound oxidative stress and impaired mitochondrial activity. Correspondingly, daily oral administration of HECB reduced actual and relative liver weights, normalized circulating hepatic enzyme activity as well as inflammatory markers, hepatic oxidative stress and restored antioxidant reserves. Further hepatic mitochondrial activity, NRF2 and TFAM levels were also improved. Hepatoprotective effect pronounced by HECB was further confirmed by histopathological analysis and phenobarbitone induced sleeping time. Nonetheless, the hepatoprotective effect was more prominently observed at 100 mg/kg dose. Conclusion Conclusively, the study provides preliminary evidence regarding hepatoprotective activity of HECB and the contribution of its antioxidant potential towards this pharmacological effect.

Publisher

Research Square Platform LLC

Reference44 articles.

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4. Cyclophosphamide toxicity. Characterising and avoiding the problem;Fraiser LH;Drugs,1991

5. Role of glutathione in the metabolism-dependent toxicity and chemotherapy of cyclophosphamide;Gurtoo HL;Cancer Res,1981

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