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Platinum-based drug-induced depletion of amino acids in the kidneys and liver.

ABSTRACT: Cisplatin (cis-diamminedichloroplatinum II; CDDP) is a widely used cytostatic agent; however, it tends to promote kidney and liver disease, which are a major signs of drug-induced toxicity. Platinum compounds are often presented as alternative therapeutics and subsequently easily dispersed in the environment as contaminants. Due to the major roles of the liver and kidneys in removing toxic materials from the human body, we performed a comparative study of the amino acid profiles in chicken liver and kidneys before and after the application of CDDP and platinum nanoparticles (PtNPs-10 and PtNPs-40). The treatment of the liver with the selected drugs affected different amino acids; however, Leu and Arg were decreased after all treatments. The treatment of the kidneys with CDDP mostly affected Val; PtNPs-10 decreased Val, Ile and Thr; and PtNPs-40 affected only Pro. In addition, we tested the same drugs on two healthy cell lines, HaCaT and HEK-293, and ultimately explored the amino acid profiles in relation to the tricarboxylic acid cycle (TCA) and methionine cycle, which revealed that in both cell lines, there was a general increase in amino acid concentrations associated with changes in the concentrations of the metabolites of these cycles.

SUBMITTER: Mitrevska K

PROVIDER: S-EPMC9535364 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Platinum-based drug-induced depletion of amino acids in the kidneys and liver.

Mitrevska Katerina K Cernei Natalia N Michalkova Hana H Rodrigo Migue Angel Merlos MAM Sivak Ladislav L Heger Zbynek Z Zitka Ondrej O Kopel Pavel P Adam Vojtech V Milosavljevic Vedran V

Frontiers in oncology 20220921

Cisplatin (cis-diamminedichloroplatinum II; CDDP) is a widely used cytostatic agent; however, it tends to promote kidney and liver disease, which are a major signs of drug-induced toxicity. Platinum compounds are often presented as alternative therapeutics and subsequently easily dispersed in the environment as contaminants. Due to the major roles of the liver and kidneys in removing toxic materials from the human body, we performed a comparative study of the amino acid profiles in chicken liver ...[more]

PMID: 36212465

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Project description:Long-term use of disease-modifying anti-rheumatic drugs (DMARDs) such as methotrexate (MTX) shows clinical benefits for rheumatoid arthritis (RA) treatment. However, there are growing concerns over the adverse effects of systemic drug administration. Therefore, a strategy that can enhance drug bioavailability while minimizing side effects is urgently needed, but remains a challenge in RA therapy. To this end, here we conjugated MTX with a supramolecular self-assembling hydrogel composed of d-amino acids with a sequence of GDFDFDY. It was shown that MTX-GDFDFDY hydrogels exhibited a favorable drug selectivity behavior that they increased MTX toxicity toward RA synoviocytes, but reduce toxicity toward normal cells. Moreover, MTX-GDFDFDY hydrogels not only effectively inhibited the proliferation and migration of RA synoviocytes, but also inhibited the polarization of proinflammatory M1 type macrophages to reduce inflammation. After intra-articularly injected the hydrogels into the joints of adjuvant induced arthritis (AIA) mice, we found that MTX-GDFDFDY hydrogels significantly alleviated RA syndromes of joint swelling and fever compared to L-configuration MTX-GFFY hydrogels and free MTX. Furthermore, MTX-GDFDFDY hydrogels successfully protected cartilage though inhibiting synovial invasion and inflammation without causing systematic side effects. Therefore, d-amino acids supramolecular hydrogels can serve as an efficient and safe drug delivery system, showing a promising potential to improve RA therapy. Graphical abstract Methotrexate (MTX) loaded supramolecular hydrogels was prepared using d-amino acids for rheumatoid arthritis (RA) therapy. The resultant MTX-GDFDFDY hydrogels exhibited selective cytotoxicity on RA synoviocytes rather than normal cells. They can also inhibit the polarization of M1 type macrophages. Therefore, MTX-GDFDFDY hydrogels successfully reduce synovial hyperplasia and joint destruction in vivo, leading to an efficient and safe RA therapy.Image 1

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Platinum-based drug-induced depletion of amino acids in the kidneys and liver.

Publications

Platinum-based drug-induced depletion of amino acids in the kidneys and liver.

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