The possible role of astaxanthin in cisplatin-induced nephrotoxicity.
The possible role of astaxanthin in cisplatin-induced nephrotoxicity in rats: interplay between non-coding RNA, redox state, inflammation, and ferroptosis: a histological, immunohistochemical, and biochemical study.
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Abstract
Cisplatin is a broad-spectrum anticancer drug with considerable place among chemotherapeutic agents. However, its adverse effect as nephrotoxicity limits its clinical use. Astaxanthin is a marine carotenoid with potent antioxidant and anti-inflammatory activity. The current work investigated the biochemical and molecular mechanisms of cisplatin-induced nephrotoxicity and astaxanthin's capacity to mitigate it. Animals were assigned to four groups: control group, astaxanthin group (25 mg/Kg intraperitoneal (i.p)) for 8 days, cisplatin group (6 mg/Kg, i.p) on the 3rd day of the experiment, and astaxanthin-cisplatin group. Biochemical, molecular, and histopathological assessments were performed to assess renal injury. Cisplatin-induced nephrotoxicity was evident by the elevated levels of blood urea nitrogen (BUN), creatinine, and renal tissue malondialdehyde (MDA) and decreased levels of reduced glutathione (GSH) in renal tissue. The cisplatin group revealed a marked rise in the gene expression of metastasis-associated lung adenocarcinoma transcription-1 (MALAT-1) and nuclear factor kappa-B (NF-κB), along with a marked reduction in the gene expression of nuclear factor erythroid 2-related factor (Nrf2), glutathione peroxidase 4 (GPX4), and microRNA(miR)-146a. The cisplatin also induced disturbed renal architecture, including shrunken glomeruli and vacuolated tubular epithelium with small dense nuclei, in addition to edema and infiltration in-between the renal parenchyma. These changes were associated with a significant increase in the immune expression of NF-κB, desmin, and Bax in the renal parenchyma. Interestingly, co-administration of astaxanthin significantly attenuated nephrotoxicity indices, gene expression variations, and histopathological changes. Taken together, findings in the current research suggested that astaxanthin protects against cisplatin-induced nephrotoxicity by inhibiting oxidative stress, inflammation, and ferroptosis via MALAT-1and miR-146a/ NF-κB /Nrf2/GPX4 signaling pathway.
Affiliation
Amany Mohamed Shalaby
External References
- PubMed ID:
- 41559443
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