article · Molecules
Cisplatin is an effective chemotherapy drug, but its clinical use is restricted by toxic side effects that damage the kidneys. This investigation explored the use of papaverine to prevent cisplatin-induced renal injury while maintaining cancer-fighting potency. Computer-based modelling predicted that papaverine targets pathways associated with kidney damage, specifically downregulating MAPK1 signalling. Laboratory experiments confirmed that papaverine protected normal kidney cells without reducing cisplatin toxicity against cancer cells. In animal trials using rats, concurrent treatment with papaverine prevented increases in kidney injury markers, oxidative stress, inflammation, and cellular death, while preserving tissue structure and boosting protective antioxidant enzymes. Overall, the findings suggest that papaverine can safeguard kidney health during cisplatin chemotherapy.
Cisplatin is a vital cancer therapy, but the severe kidney damage it causes often forces doctors to limit dosages or halt treatment entirely. Finding an adjunct compound that guards kidney function without diminishing anti-tumour strength could allow safer, more effective chemotherapy regimens for cancer patients.
This research could support the development of adjuvant therapeutics or co-formulations used alongside cisplatin to prevent acute kidney injury during cancer treatment. Potential users include oncologists and pharmaceutical companies developing supportive care therapies. As testing has only reached in vitro and rodent stages, the concept remains in early-stage preclinical research, requiring further studies before any clinical translation.
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Cisplatin is a potent compound in anti-tumor chemotherapy; however, its clinical utility is hampered by dose-limiting nephrotoxicity. This study investigated whether papaverine could mitigate cisplatin-induced kidney damage while preserving its chemotherapeutic efficacy. Integrative bioinformatics analysis predicted papaverine modulation of the mechanistic pathways related to cisplatin renal toxicity; notably, mitogen-activated protein kinase 1 (MAPK1) signaling. We validated protective effects in normal kidney cells without interfering with cisplatin cytotoxicity on a cancer cell line. Concurrent in vivo administration of papaverine alongside cisplatin in rats prevented elevations in nephrotoxicity markers, including serum creatinine, blood urea nitrogen, and renal oxidative stress markers (malondialdehyde, inducible nitric oxide synthase (iNOS), and pro-inflammatory cytokines), as tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein 1 (MCP-1), and interleukin-6 (IL-6). Papaverine also reduced apoptosis markers such as Bcl2 and Bcl-2-associated X protein (Bax) and kidney injury molecule-1 (KIM-1), and histological damage. In addition, it upregulates antioxidant enzymes like catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) while boosting anti-inflammatory signaling interleukin-10 (IL-10). These effects were underlined by the ability of Papaverine to downregulate MAPK-1 expression. Overall, these findings show papaverine could protect against cisplatin kidney damage without reducing its cytotoxic activity. Further research would allow the transition of these results to clinical practice.
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DOI: 10.3390/molecules29091927
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