Boswellic acids ameliorate doxorubicin-induced nephrotoxicity in mice: a focus on antioxidant and antiapoptotic effects

ABSTRACT

Doxorubicin (DXR) is a broad-spectrum anti-cancer. Doxorubicin irreversible toxicity resulting from oxidative damage limits its therapeutic use. Boswellic acids (BAs) are inhibitors of 5-lipoxygenase and have been used in traditional medicine for their powerful anti-inflammatory effects and cellular protective effects. This study tested the protecting mechanisms of BAs against nephrotoxicity induced by DXR in mice and explored their antioxidant and antiapoptotic activities in the form of immunohistochemical expression of Bcl2 in the tissue of the kidney. DXR (6 mg/kg) was injected intraperitoneally weekly to mice along with BAs (125, 250 and 500 mg/kg) daily. The experiment continued for three weeks. It was found that the elevated serum urea and creatinine in DXR-treated mice were ameliorated by BAs. Furthermore, BAs decreased malondialdehyde and increased glutathione levels in renal tissues of DXR-treated mice. The immunostained kidney tissue showed an anti-apoptotic effect for BAs as it increased expression of Bcl2 in mice co-treated with BAs with DXR compared to the DXR control mice. Western blot analysis demonstrated that DXR control group showed greater expression for renal caspase 3 and mice administered BAs (125–500 mg/kg) along with DXR showed significant downregulations. These findings were supported by the DNA laddering assay and histopathological examination of renal tissues stained with haematoxylin+eosin or periodic acid Schiff. Results suggest BAs for nephroprotection against toxicity induced by DXR.

KEYWORDS:

• Antioxidant
• apoptosis
• boswellic acids
• doxorubicin
• mouse
• nephroprotection

Research Highlights

1. This study indicated that Boswellic acids (BAs) ameliorated doxorubicin (DXR)-induced nephrotoxicity in mice.

2. This effect is at least in part mediated by antiapoptotic and antioxidant effects.

3. BAs decreased malondialdehyde and increased glutathione levels in renal tissues of DXR-treated mice.

4. Caspase-3 showed greater expression in DXR group and significant downregulation in mice treated with BAs.

5. BCl₂ showed higher expression in groups co-treated with BAs along with DXR than the DXR-treated mice thus implies an anti-apoptotic effect for BAs.

Acknowledgments

Researchers wish to acknowledge the Central Lab. of the “Center of Excellence in Molecular and Cellular Medicine (CEMCM)” for using the labs in capturing the histopathology and immunostaining pictures.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work did not receive funding from any organizations