Ambroxol attenuates cisplatin-induced hepatotoxicity and nephrotoxicity via inhibition of p-JNK/p-ERK

Abstract

Hepatotoxicity and nephrotoxicity are important drawbacks of cisplatin. The objective of this study is to evaluate the ability of ambroxol in 2 different doses (35 and 70 mg/kg, i.p.) to protect liver and kidney from damage induced by a single dose of cisplatin (10 mg/kg, i.p.) in comparison with N-acetylcysteine (250 mg/kg, i.p.). Inflammatory, oxidative stress, and apoptotic biomarkers were investigated to show the influence of ambroxol on hepatotoxicity and nephrotoxicity. Ambroxol decreased the elevated activity of liver enzymes (aspartate aminotransferase and alanine aminotransferase) and kidney function tests (blood urea nitrogen and creatinine). Ambroxol mitigated cisplatin inflammatory damage by inhibition of tumor necrosis factor-α, interleukin-1β, and nuclear factor kappa-B and elevation of nuclear factor erythroid 2-related factor 2. Moreover, ambroxol inhibited oxidative damage indicated by reduction of malondialdehyde and replenished the store of reduced glutathione likely by upregulating glutathione reductase and superoxide dismutase. Elevation of phosphorylated c-Jun N-terminal kinases (p-JNK) and phosphorylated extracellular signal-regulated kinase (p-ERK) were attenuated by ambroxol associated with a decrease in the expression of caspase-3; these results were consistent with histopathological results. These results recommend ambroxol to be co-administered with cisplatin in cancer patients to ameliorate liver and kidney damage, and this was confirmed by MTT assay.

Polygonum minus essential oil modulates cisplatin-induced hepatotoxicity through inflammatory and apoptotic pathways

“…Increased level of MDA and reduction in antioxidant status (GSH, GPx, SOD, and catalase) were observed in the cisplatin treated rats and this is in agreement with previous studies, i.e. Bishr and colleagues (2018[ 13 ]) as well as Ahmadipour and colleagues (2015[ 3 ]). GSH plays an important role in the detoxification of cisplatin and cell death occurs when GSH is markedly exhausted (Ince et al, 2014[ 41 ]).…”

“…β-Caryophyllene served as positive control. All animals except for those in the control group and PmEO400 group were administered with a single dose of cisplatin (10 mg/kg) intraperitoneally (Bishr et al, 2018[ 13 ]) on day 15, left untreated for three days and were sacrificed humanely on day 18 (Palipoch and Punsawad 2013[ 63 ]). Blood samples were collected via cardiac puncture, whereas liver was excised for further analysis.…”

P-Glycoprotein/ABCB1 Might Contribute to Morphine/Cisplatin-Induced Hepatotoxicity in Rats

“…Here, the present study showed for the first time that MOR/CP combination enhanced of hepatic inflammation by inducing TNF-α/IL-6 pathway. The present study also showed that CP induced apoptosis by up-regulating caspase 3, which was expected from previous studies [3,6,23]. MOR alone also up-regulated caspase 3 in the liver.…”

<p>MiR-124-3p.1 Sensitizes Ovarian Cancer Cells to Mitochondrial Apoptosis Induced by Carboplatin</p>

“…7 Cisplatin is an effective treatment but causes nephrotoxicity. [8][9][10] Carboplatin, by contrast, exhibits cytotoxicity against ovarian cancer cells without obvious nephrotoxicity. 11,12 However, resistance to carboplatin is a major obstacle to achieving satisfactory effects in ovarian cancer treatment.…”