Amelioration of Cisplatin-induced Renal Inflammation by Recombinant Human Golimumab in Mice.
Cis-platin
Golimumab
anti-TNF biologics
anti-cancer agents
human recombinant golimumab
renal inflammation
Journal
Current pharmaceutical biotechnology
ISSN: 1873-4316
Titre abrégé: Curr Pharm Biotechnol
Pays: Netherlands
ID NLM: 100960530
Informations de publication
Date de publication:
2022
2022
Historique:
received:
29
01
2021
revised:
31
05
2021
accepted:
12
06
2021
pubmed:
10
2
2022
medline:
13
4
2022
entrez:
9
2
2022
Statut:
ppublish
Résumé
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. Current study has explored the effects of anti-TNF biologics golimumab on mice due to cisplatin-induced nephrotoxicity. 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. 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. 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.
Sections du résumé
BACKGROUND
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
OBJECTIVE
Current study has explored the effects of anti-TNF biologics golimumab on mice due to cisplatin-induced nephrotoxicity.
METHOD
METHODS
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 35135447
pii: CPB-EPUB-117242
doi: 10.2174/1389201022666210810141139
doi:
Substances chimiques
Antibodies, Monoclonal
0
Transforming Growth Factor beta1
0
Tumor Necrosis Factor Inhibitors
0
Intercellular Adhesion Molecule-1
126547-89-5
Interleukin-10
130068-27-8
golimumab
91X1KLU43E
Cisplatin
Q20Q21Q62J
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
970-977Subventions
Organisme : Lupin Biotech Limited
ID : 2030/PO/RCBIBT/S/18/CPCSEA
Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.