Protective Effects of Orexin A in a Murine Model of Cisplatin-Induced Acute Kidney Injury

Abstract

Cisplatin is a chemotherapeutic agent widely used in the treatment of various cancers, but its application is often limited due to complications such as acute kidney injury (AKI). Orexins are hypothalamic neuropeptides that modulate the sleep-wake cycle, neuroendocrine function, and the autonomic nervous system. Emerging evidence suggests that orexin A (OXA) has anti-inflammatory and neuroprotective effects in animal models of neuroinflammatory diseases of the central nervous system. However, the effect of OXA on kidney diseases has not been examined. Here, we investigated whether OXA has a protective effect in a murine model of cisplatin-induced AKI. Intraperitoneal administration of OXA ameliorated renal dysfunction, and histological abnormalities in mice injected with cisplatin. OXA inhibited cisplatin-induced oxidative stress through the modulation of prooxidant and antioxidant enzymes. This peptide reduced apoptotic cell death by inhibiting the p53-mediated pathway in mice injected with cisplatin. OXA also alleviated cisplatin-induced cytokine production and macrophage infiltration into injured kidneys. Taken together, these results showed that OXA ameliorates cisplatin-induced AKI via antioxidant, anti-apoptotic, and anti-inflammatory actions. This peptide could be a potential therapeutic agent for cisplatin-induced AKI.

6-Shogaol Ameliorates Liver Inflammation and Fibrosis in Mice on a Methionine- and Choline-Deficient Diet by Inhibiting Oxidative Stress, Cell Death, and Endoplasmic Reticulum Stress

“…Given the well-established critical role of oxidative stress in NASH pathogenesis [ 4 ], we conducted an investigation into the impact of 6-shogaol on oxidative stress to elucidate the mechanisms responsible for its protective effects against NASH. IHC staining of 4-hydroxynonenal (4-HNE), a recognized biomarker for lipid oxidative damage [ 22 ], revealed elevated hepatic expression of 4-HNE in MCD-diet-fed mice ( p < 0.001; Figure 5 A,B). Notably, the administration of 6-shogaol markedly reduced 4-HNE expression in mice exposed to the MCD diet ( p < 0.001; Figure 5 A,B).…”

Antioxidant, Antiapoptotic, and Anti-Inflammatory Effects of Hesperetin in a Mouse Model of Lipopolysaccharide-Induced Acute Kidney Injury

“…However, hesperetin treatment alleviated LPS-induced renal tubular structural damages (tubular injury score: LPS, 2.4 ± 0.3 vs. LPS+Hes, 1.1 ± 0.2, p < 0.01; Figure 1 B,C). Next, the brush border of proximal tubules was visualized using a fluorescein isothiocyanate (FITC)-conjugated lotus tetragonolobus lectin (LTL) to examine the brush border loss [ 26 , 27 ]. Immunofluorescence (IF) staining revealed that LPS injection reduced the percentage of the LTL-stained area, but this change was mitigated by hesperetin (LPS, 4.1 ± 1.0% vs. LPS+Hes, 9.1 ± 1.4%, p < 0.05; Figure 1 D,E).…”

Involvement of the Orexinergic System in Cancer: Antitumor Strategies and Future Perspectives

“…This must be investigated in depth, since orexin A could act as an anti-emetic agent and it could be used against vomiting in patients with cancer who have received chemotherapy. Moreover, orexin A improved cisplatin-induced acute kidney injury, exerting anti-inflammatory, anti-apoptotic and antioxidant effects [143], and orexin A improved the gastric disorders promoted by cisplatin in rodents. It seems that the peptide acted via the peptidergic neurons containing neuropeptide Y located in the hypothalamic arcuate nucleus [144].…”