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 antiapoptotic 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.

Ameliorative Effects of Boswellic Acid on Fipronil-Induced Toxicity: Antioxidant State, Apoptotic Markers, and Testicular Steroidogenic Expression in Male Rats

“…with non-significant improvement in the BA higher dose concerning the lower dose of BA. The obtained result was in the same line with Sami et al [ 21 ] in which they reported the nephroprotective effect of BA with a non-significant improvement of the higher dose of BA (500 mg/kg) due to the antioxidant and antiapoptotic effect of boswellic acid.…”

“…Conversely, rats that received FPN plus BA (250 and 500 mg/kg) showed significant enhancement of most seminiferous tubules’ spermatogenesis by including elongated spermatids and spermatozoa. These results were inconsistent with [ 21 ] in which they reported that the most convenient restoration of these parameters was achieved in the doxorubicin + BA 500 mg/kg group. Supporting our result, data obtained by Kruger et al [ 57 ] have reported antioxidants and chelate metals of BAs in oxidative injury pathways.…”

“…BA treatment (250 and 500 mg/kg) normalizes the apoptotic effect of FPN, which is cleared by our result, in which FPN significantly upregulates Bax, heat shock protein, and gene expression with significant downregulation to Bcl-2. These results show inconsistency with [ 21 ]; they revealed the antioxidant and antiapoptotic effects of BA. BA’s prospective role in the scavenging of FPN ROS was linked in histological architecture to testes, the epididymis, and sexual accessory glands.…”

“…The utilized doses of boswellic acid in the current study were tested previously as reported by Sami et al [ 21 ] in which they found that boswellic acids can ameliorate doxorubicin-induced nephrotoxicity in mice, they used different doses of boswellic acid (125 mg/kg), (250 mg/kg), and (500 mg/kg), and they found that the effect of the high dose of BAs (500 mg/kg) was different (more ameliorative) from that observed with the lowest dose (125 mg/kg). In the same line, Nusier et al [ 20 ] studied the effect of two different doses of boswellic acid: 250 and 500 mg/kg.…”

“…Rats were randomly assigned to six equivalent groups (six rats/each) as follows: Group 1 (control) rats were orally administered with two ml physiological saline/kg body weight (bwt) (a vehicle for other drugs); Group 2 (BA1) rats were orally administered 250 mg BA/kg bwt; Group 3 (BA2) rats were orally administered 500 mg BA/kg bwt according to Nusier et al [ 20 ]. The utilized doses of boswellic acid in the current study were tested previously as showed by Sami et al [ 21 ] and Nusier et al [ 20 ] as well as Barakat et al [ 22 ] and Tawfik et al [ 23 ]. Al-Yahya et al [ 24 ] reported that the boswellic acid is safe up to 1000 mg/kg in rats.…”