Abstract
Background: One of the most commonly used anti-cancer agents, Cisplatin (CDDP) often causes nephrotoxicity by eliciting inflammation and oxidative stress. Golimumab, an anti-TNF biologic, is prescribed for the management of numerous inflammatory ailments like psoriatic and rheumatoid arthritis, ulcerative colitis and ankylosing spondylitis.
Objective: Current study has explored the effects of anti-TNF biologics golimumab on mice due to cisplatin-induced nephrotoxicity.
Method: Renal toxicity was caused by administration of single cisplatin injection at 22 mg/kg by intraperitoneal (i/p) route. Golimumab (24 mg/kg, s.c.) was administered consecutively for 7 days. The parameters such as renal functions, oxidative stress, inflammation, and renal damage were evaluated on the 7th day of experiments.
Results: Cisplatin administration caused nephrotoxicity as shown by a significant elevation of various parameters viz; serum creatinine, neutrophil gelatinase-associated lipocalin (NGAL), urea nitrogen (BUN), and cystatin C. There was a significant rise in urinary clusterin, kidney injury molecule 1 (KIM-1), and β-N-acetylglucosaminidase (NAG) concentrations in the animals treated with cisplatin. The markers of oxidative stress (malondialdehyde, reduced glutathione, and catalase), inflammation (IL-6, TNF-α, IL-10, IL-1β, MCP-1, ICAM-1, and TGF-β1), and apoptosis (caspase-3) were also altered in serum and/or kidneys of cisplatin animals. Further, cisplatin-caused histopathological changes in proximal tubular cells as observed in the H&E staining of renal tissue. Golimumab treatment reduced all markers of kidney injury and attenuated cell death. Golimumab significantly reduced inflammatory cytokines TNFα, IL- 6, MCP-1, IL- 1β, ICAM-1, and TGF-β1 and increased anti-inflammatory cytokine IL-10 in cisplatin-intoxicated mice.
Conclusion: The study’s results suggest that golimumab prevented nephrotoxicity induced by cisplatin- through inhibition of oxidative stress, apoptotic cell death inflammatory response, thus improving renal function.
Keywords: Golimumab, Cis-platin, renal inflammation, human recombinant golimumab, anti-TNF biologics, anti-cancer agents.
[http://dx.doi.org/10.1016/j.ejphar.2014.07.025] [PMID: 25058905]
[http://dx.doi.org/10.1006/taap.1997.8325] [PMID: 9512723]
[PMID: 18185852]
[http://dx.doi.org/10.13005/bpj/1250]
[http://dx.doi.org/10.1016/j.tox.2016.10.001] [PMID: 27717837]
[http://dx.doi.org/10.5935/0101-2800.20130052] [PMID: 24402113]
[http://dx.doi.org/10.1016/j.ejphar.2020.173339] [PMID: 32726655]
[http://dx.doi.org/10.1056/NEJM199704103361506] [PMID: 9091804]
[http://dx.doi.org/10.1016/j.etp.2008.09.003] [PMID: 18986801]
[http://dx.doi.org/10.1172/JCI200215606] [PMID: 12235115]
[http://dx.doi.org/10.4161/mabs.1.5.9286] [PMID: 20065639]
[http://dx.doi.org/10.2147/CEG.S48741] [PMID: 24648749]
[http://dx.doi.org/10.1155/2017/3140680] [PMID: 28831294]
[http://dx.doi.org/10.1016/j.fct.2019.04.031] [PMID: 31014901]
[http://dx.doi.org/10.1634/theoncologist.2016-0319] [PMID: 28438887]
[http://dx.doi.org/10.1007/s40620-017-0392-z] [PMID: 28382507]
[http://dx.doi.org/10.3390/toxins2112490] [PMID: 22069563]
[http://dx.doi.org/10.1007/s00210-018-1564-7] [PMID: 30206656]
[http://dx.doi.org/10.2478/acph-2020-0033] [PMID: 32412432]
[http://dx.doi.org/10.1016/j.ejphar.2013.05.023] [PMID: 23747596]
[http://dx.doi.org/10.1155/2013/361078] [PMID: 23476755]
[http://dx.doi.org/10.1177/0192623312444765] [PMID: 22581811]
[http://dx.doi.org/10.1155/MI.2005.139] [PMID: 16106099]
[http://dx.doi.org/10.1111/and.12197] [PMID: 24266675]
[http://dx.doi.org/10.1016/j.tox.2014.07.004] [PMID: 25043994]
[http://dx.doi.org/10.1016/j.cca.2006.06.011] [PMID: 16889761]
[http://dx.doi.org/10.1016/j.phrs.2009.07.007] [PMID: 19647078]
[http://dx.doi.org/10.3109/0886022X.2013.829405] [PMID: 24001301]
[http://dx.doi.org/10.1046/j.1523-1755.2001.00043.x] [PMID: 11737586]
[http://dx.doi.org/10.1093/toxsci/63.2.196] [PMID: 11568363]
[http://dx.doi.org/10.1097/00007890-200003150-00049] [PMID: 10755557]
[http://dx.doi.org/10.1172/JCI119457] [PMID: 9169498]
[http://dx.doi.org/10.1681/ASN.V10112314] [PMID: 10541290]
[http://dx.doi.org/10.1152/ajpregu.1999.277.3.R922] [PMID: 10484513]
[http://dx.doi.org/10.1046/j.1523-1755.2001.00026.x] [PMID: 11703590]
[http://dx.doi.org/10.1016/j.biologicals.2019.09.007] [PMID: 31558429]
[http://dx.doi.org/10.2174/1389200220666190614150708] [PMID: 31203796]
[http://dx.doi.org/10.2174/1389200219666180305154119] [PMID: 29512450]