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Pharmaceutical strategies for preventing toxicity and promoting antioxidant and anti-inflammatory actions of bilirubin.

ABSTRACT: Bilirubin (BR) is the final product of haem catabolism. Disruptions along BR metabolic/transport pathways resulting from inherited disorders can increase plasma BR concentration (hyperbilirubinaemia). Unconjugated hyperbilirubinemia may induce BR accumulation in brain, potentially causing irreversible neurological damage, a condition known as BR encephalopathy or kernicterus, to which newborns are especially vulnerable. Numerous pharmaceutical strategies, mostly based on hemoperfusion, have been proposed over the last decades to identify new valid, low-risk alternatives for BR removal from plasma. On the other hand, accumulating evidence indicates that BR produces health benefits due to its potent antioxidant, anti-inflammatory and immunomodulatory action with a significant potential for the treatment of a multitude of diseases. The present manuscript reviews both such aspects of BR pharmacology, gathering literature data on applied pharmaceutical strategies adopted to: (i) reduce the plasma BR concentration for preventing neurotoxicity; (ii) produce a therapeutic effect based on BR efficacy in the treatment of many disorders.

SUBMITTER: Nocentini A

PROVIDER: S-EPMC8741241 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Pharmaceutical strategies for preventing toxicity and promoting antioxidant and anti-inflammatory actions of bilirubin.

Nocentini Alessio A Bonardi Alessandro A Pratesi Simone S Gratteri Paola P Dani Carlo C Supuran Claudiu T CT

Journal of enzyme inhibition and medicinal chemistry 20221201 1

Bilirubin (BR) is the final product of haem catabolism. Disruptions along BR metabolic/transport pathways resulting from inherited disorders can increase plasma BR concentration (hyperbilirubinaemia). Unconjugated hyperbilirubinemia may induce BR accumulation in brain, potentially causing irreversible neurological damage, a condition known as BR encephalopathy or kernicterus, to which newborns are especially vulnerable. Numerous pharmaceutical strategies, mostly based on hemoperfusion, have been ...[more]

PMID: 34986721

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Project description:BackgroundThe heavy metals cause repro-toxicity via oxidative stress and suppress the antioxidant enzymes. Kaempferol and vitamin E possess antioxidant properties that can counteract the deleterious heavy metals effects.AimThe present study was directed to investigate the protective role of kaempferol, alone or with vitamin E, on testicular toxicity mediated by lead acetate in male rats.MethodsFifty adult male rats were randomly grouped into five groups (n = 10): the control group received 5 ml distilled water, and the Pb group was intraperitoneally injected with 20 mg/kg of lead acetate. The Pb + Vitamin E group received Pb with 100 mg/kg of vitamin E, the Pb + KAF group received Pb with 50 mg/kg of kaempferol, the Pb + KAF + Vitamin E group received Pb with kaempferol and vitamin E for 6 weeks.ResultsThe testicular levels of superoxide dismutase, catalase, steroidogenic enzyme, serum testosterone, follicle-stimulating hormone, interleukin (IL)-10, and sperm function were significantly decreased in the Pb group compared with all experimental groups. These parameters were significantly elevated in the Pb + KAF + Vitamin E group compared to other experimental groups. Lead acetate caused elevation in testicular malondialdehyde, nitric oxide, IL-6, IL-1β, tumor necrosis factor-α, nuclear factor kappa, and sperm abnormality compared to all treatment groups. All these parameters were significantly declined in the Pb + KAF + Vitamin E group and Pb + KAF group compared with the Pb group. The fold changes of pituitary follicle-stimulating hormone beta, gonadotropin-releasing hormone receptor, and luteinizing hormone beta, and testicular CYP11A1, LH receptor, and FHr gene expression were significantly upregulated in Pb + KAF + Vitamin E group compared with all experimental groups. In addition, KAF + Vitamin E has the potential to improve testicular regeneration in seminiferous tubules, Leydig, and Sertoli cells.ConclusionAdministration of kaempferol alone or with vitamin E can mitigate lead acetate-induced testicular toxicity in rats via its antioxidant and anti-inflammatory properties. The current research is the first to demonstrate that kaempferol can exert a preventive role in testicular dysfunction.

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Pharmaceutical strategies for preventing toxicity and promoting antioxidant and anti-inflammatory actions of bilirubin.

Publications

Pharmaceutical strategies for preventing toxicity and promoting antioxidant and anti-inflammatory actions of bilirubin.

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